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Pepsin

Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids. It is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pepsin is an aspartic protease, using a catalytic aspartate in its active site.

It is one of three principal endopeptidases (enzymes cutting proteins in the middle) in the human digestive system, the other two being chymotrypsin and trypsin. There are also exopeptidases which remove individual amino acids at both ends of proteins (carboxypeptidases produced by the pancreas and aminopeptidases secreted by the small intestine). During the process of digestion, these enzymes, each of which is specialized in severing links between particular types of amino acids, collaborate to break down dietary proteins into their components, i.e., peptides and amino acids, which can be readily absorbed by the small intestine. The cleavage specificity of pepsin is broad, but some amino acids like tyrosine, phenylalanine and tryptophan increase the probability of cleavage.

Pepsin's zymogen (proenzyme), pepsinogen, is released by the gastric chief cells in the stomach wall, and upon mixing with the hydrochloric acid of the gastric juice, pepsinogen activates to become pepsin.

History
Pepsin was one of the first enzymes to be discovered, by Theodor Schwann in 1836. Schwann coined its name from the Greek word πέψις pepsis, meaning "digestion" (from πέπτειν peptein "to digest"). An acidic substance that was able to convert nitrogen-based foods into water-soluble material was determined to be pepsin.

In 1928, it became one of the first enzymes to be crystallized when John H. Northrop crystallized it using dialysis, filtration, and cooling.

Precursor
Pepsin is expressed as a zymogen called pepsinogen, whose primary structure has an additional 44 amino acids compared to the active enzyme.

In the stomach, gastric chief cells release pepsinogen. This zymogen is activated by hydrochloric acid (HCl), which is released from parietal cells in the stomach lining. The hormone gastrin and the vagus nerve trigger the release of both pepsinogen and HCl from the stomach lining when food is ingested. Hydrochloric acid creates an acidic environment, which allows pepsinogen to unfold and cleave itself in an autocatalytic fashion, thereby generating pepsin (the active form). Pepsin cleaves the 44 amino acids from pepsinogen to create more pepsin.

Pepsinogens are mainly grouped in 5 different groups based on their primary structure: pepsinogen A (also called pepsinogen I), pepsinogen B, progastricsin (also called pepsinogen II and pepsinogen C), prochymosin (also called prorennin) and pepsinogen F (also called pregnancy-associated glycoprotein).

Activity and stability
Pepsin is most active in acidic environments between pH 1.5 to 2.5. Accordingly, its primary site of synthesis and activity is in the stomach (pH 1.5 to 2). In humans the concentration of pepsin in the stomach reaches 0.5 – 1 mg/mL.

Pepsin is inactive at pH 6.5 and above, however pepsin is not fully denatured or irreversibly inactivated until pH 8.0. Therefore, pepsin in solutions of up to pH 8.0 can be reactivated upon re-acidification. The stability of pepsin at high pH has significant implications on disease attributed to laryngopharyngeal reflux. Pepsin remains in the larynx following a gastric reflux event. At the mean pH of the laryngopharynx (pH = 6.8) pepsin would be inactive but could be reactivated upon subsequent acid reflux events resulting in damage to local tissues.

Pepsin exhibits a broad cleavage specificity. Pepsin will digest up to 20% of ingested amide bonds. Residues in the P1 and P1' positions are most important in determining cleavage probability. Generally, hydrophobic amino acids at P1 and P1' positions increase cleavage probability. Phenylalanine, leucine and methionine at the P1 position, and phenylalanine, tryptophan and tyrosine at the P1' position result in the highest cleavage probability. Cleavage is disfavoured by positively charged amino acids histidine, lysine and arginine at the P1 position.

In laryngopharyngeal reflux
Pepsin is one of the primary causes of mucosal damage during laryngopharyngeal reflux. Pepsin remains in the larynx (pH 6.8) following a gastric reflux event. While enzymatically inactive in this environment, pepsin would remain stable and could be reactivated upon subsequent acid reflux events. Exposure of laryngeal mucosa to enzymatically active pepsin, but not irreversibly inactivated pepsin or acid, results in reduced expression of protective proteins and thereby increases laryngeal susceptibility to damage.

Pepsin may also cause mucosal damage during weakly acidic or non-acid gastric reflux. Weak or non-acid reflux is correlated with reflux symptoms and mucosal injury. Under non-acid conditions (neutral pH), pepsin is internalized by cells of the upper airways such as the larynx and hypopharynx by a process known as receptor-mediated endocytosis. The receptor by which pepsin is endocytosed is currently unknown. Upon cellular uptake, pepsin is stored in intracellular vesicles of low pH at which its enzymatic activity would be restored. Pepsin is retained within the cell for up to 24 hours. Such exposure to pepsin at neutral pH and endocyctosis of pepsin causes changes in gene expression associated with inflammation, which underlies signs and symptoms of reflux, and tumor progression. This and other research implicates pepsin in carcinogenesis attributed to gastric reflux.

Pepsin in airway specimens is considered to be a sensitive and specific marker for laryngopharyngeal reflux. Research to develop new pepsin-targeted therapeutic and diagnostic tools for gastric reflux is ongoing. A rapid non-invasive pepsin diagnostic called Peptest is now available which determines the presence of pepsin in saliva samples.

Inhibitors
Pepsin may be inhibited by high pH (see Activity and stability) or by inhibitor compounds. Pepstatin is a low molecular weight compound and potently inhibitor specific for acid proteases with an inhibitory dissociation constant (Ki) of about 10−10 M for pepsin. The statyl residue of pepstatin is thought to be responsible for pepstatin inhibition of pepsin; statine is a potential analog of the transition state for catalysis by pepsin and other acid proteases. Pepstatin does not covalently bind pepsin and inhibition of pepsin by pepstatin is therefore reversible. 1-bis(diazoacetyl)-2-phenylethane reversibly inactivates pepsin at pH 5, a reaction which is accelerated by the presence of Cu(II).

Porcine pepsin is inhibited by pepsin inhibitor-3 (PI-3) produced by the large roundworm of pig (Ascaris suum). PI-3 occupies the active site of pepsin using its N-terminal residues and thereby blocks substrate binding. Amino acid residues 1 - 3 (Gln-Phe-Leu) of mature PI-3 bind to P1' - P3' positions of pepsin. The N-terminus of PI-3 in the PI-3:pepsin complex is positioned by hydrogen bonds which form an eight-stranded β-sheet, where three strands are contributed by pepsin and five by PI-3.

A product of protein digestion by pepsin inhibits the reaction.

Sucralfate, a drug used to treat stomach ulcers and other pepsin-related conditions, also inhibits pepsin activity.

Applications

Commercial pepsin is extracted from the glandular layer of hog stomachs. It is a component of rennet used to curdle milk during the manufacture of cheese. Pepsin is used for a variety of applications in food manufacturing: to modify and provide whipping qualities to soy protein and gelatin, to modify vegetable proteins for use in nondairy snack items, to make precooked cereals into instant hot cereals, and to prepare animal and vegetable protein hydrolysates for use in flavoring foods and beverages. It is used in the leather industry to remove hair and residual tissue from hides and in the recovery of silver from discarded photographic films by digesting the gelatin layer that holds the silver. Pepsin was historically an additive of Beeman's gum brand chewing gum by Dr. Edwin E. Beeman.

Pepsin is commonly used in the preparation of F(ab')2 fragments from antibodies. In some assays, it is preferable to use only the antigen-binding (Fab) portion of the antibody. For these applications, antibodies may be enzymatically digested to produce either an Fab or an F(ab')2 fragment of the antibody. To produce an F(ab')2 fragment, IgG is digested with pepsin, which cleaves the heavy chains near the hinge region. One or more of the disulfide bonds that join the heavy chains in the hinge region are preserved, so the two Fab regions of the antibody remain joined together, yielding a divalent molecule (containing two antibody binding sites), hence the designation F(ab')2. The light chains remain intact and attached to the heavy chain. The Fc fragment is digested into small peptides. Fab fragments are generated by cleavage of IgG with papain instead of pepsin. Papain cleaves IgG above the hinge region containing the disulfide bonds that join the heavy chains, but below the site of the disulfide bond between the light chain and heavy chain. This generates two separate monovalent (containing a single antibody binding site) Fab fragments and an intact Fc fragment. The fragments can be purified by gel filtration, ion exchange, or affinity chromatography.

Fab and F(ab')2 antibody fragments are used in assay systems where the presence of the Fc region may cause problems. In tissues such as lymph nodes or spleen, or in peripheral blood preparations, cells with Fc receptors (macrophages, monocytes, B lymphocytes, and natural killer cells) are present which can bind the Fc region of intact antibodies, causing background staining in areas that do not contain the target antigen. Use of F(ab')2 or Fab fragments ensures that the antibodies are binding to the antigen and not Fc receptors. These fragments may also be desirable for staining cell preparations in the presence of plasma, because they are not able to bind complement, which could lyse the cells. F(ab')2, and to a greater extent Fab, fragments allow more exact localization of the target antigen, i.e., in staining tissue for electron microscopy. The divalency of the F(ab')2 fragment enables it to cross-link antigens, allowing use for precipitation assays, cellular aggregation via surface antigens, or rosetting assays.

Genes
The following three genes encode identical human pepsinogen A enzymes:

A fourth human gene encodes gastricsin also known as pepsinogen C:

title: Pepsin


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1965 in politics

This is a list of events in 1965 in politics.

January

 * January 14 - The Prime Minister of Northern Ireland and the Taoiseach of the Republic of Ireland meet for the first time in 43 years.
 * January 20 - Lyndon B. Johnson is sworn in for a full term as President of the United States.
 * January 20 - Indonesian President Sukarno announces the withdrawal of the Indonesian government from the United Nations.

February

 * February 18 - The Gambia becomes independent from the United Kingdom.
 * February 21 - African-American Muslim minister and human rights activist Malcolm X is assassinated in New York City.
 * February 23 - Herberts Cukurs, a Latvian aviator, mass murderer and former Nazi collaborator is unofficially executed by Mossad.

March

 * March 7 - Bloody Sunday: Some 200 Alabama State Troopers attack 525 civil rights demonstrators in Selma, Alabama, as they attempt to march to the state capitol of Montgomery.
 * March 8 - Some 3,500 United States Marines arrive in Da Nang, South Vietnam, becoming the first American ground combat troops in Vietnam.
 * March 9 - The second attempt, known as "Turnaround Tuesday", to march from Selma to Montgomery, Alabama, under the leadership of Martin Luther King Jr., stops at the bridge that was the site of Bloody Sunday, to hold a prayer service and return to Selma.
 * March 16 - Police clash with 600 Student Nonviolent Coordinating Committee marchers in Montgomery, Alabama.
 * March 17 - In response to the events of March 7 and 9 in Selma, Alabama, President Lyndon B. Johnson sends a bill to Congress that forms the basis for the Voting Rights Act of 1965. It is passed by the Senate May 26, the House July 10, and signed into law by President Johnson August 6.
 * March 18 - A United States federal judge rules that SCLC has the lawful right to march to Montgomery, Alabama, to petition for "redress of grievances".
 * March 20 - The Indo-Pakistani War of 1965 begins.
 * March 22 – Nicolae Ceaușescu becomes the first secretary of the Romanian Communist Party, after the death of previous leader Gheorghe Gheorghiu Dej earlier that year.
 * March 23 - Large student demonstration in Morocco, joined by discontented masses, is met with violent police and military repression.
 * March 25 - Martin Luther King Jr. and 25,000 civil rights activists successfully complete the 4-day march from Selma, Alabama, to the capitol in Montgomery.
 * March 30 - The second ODECA charter, signed on December 12, 1962, becomes effective.

April

 * April 9 - The West German parliament extends the statute of limitations on Nazi war crimes.
 * April 17 - The first Students for a Democratic Society march against the Vietnam War draws 25,000 protestors to Washington, D.C.
 * April 24 - The 1965 Yerevan demonstrations start in Yerevan, demanding recognition of the Armenian genocide.
 * April 24 - In the Dominican Republic, officers and civilians loyal to deposed President Juan Bosch against the right-wing junta running the country, setting up a provisional government. Forces loyal to the deposed military-imposed government stage a countercoup the next day, and civil war breaks out
 * April 28 - U.S. troops occupy the Dominican Republic.
 * April 29 - Australia announces that it is sending an infantry battalion to support the South Vietnam government.

May

 * May 1 - Bob Askin replaces Jack Renshaw as Premier of New South Wales.
 * May 12 - West Germany and Israel establish diplomatic relations.
 * May 22 - Several hundred Vietnam War protesters in Berkeley, California, march to the Draft Board again to burn 19 more cards. Lyndon Johnson is hung in effigy.

June

 * June 10 - Vietnam War – Battle of Dong Xoai: About 1,500 Viet Cong mount a mortar attack on Đồng Xoài, overrunning its military headquarters and the adjoining militia compound.
 * June 19 - Houari Boumediene's Revolutionary Council ousts Ahmed Ben Bella, in a bloodless coup in Algeria.
 * June 20 - Police in Algiers break up demonstrations by people who have taken to the streets chanting slogans in support of deposed President Ahmed Ben Bella.
 * June 22 - The Treaty on Basic Relations between Japan and the Republic of Korea is signed in Tokyo.

July

 * July 1 - The Commonwealth is created.
 * July 15 - Greek Prime minister Georgios Papandreou and his government are dismissed by King Constantine II.
 * July 26 - The Maldives receive full independence from Great Britain.
 * July 27 - Edward Heath becomes Leader of the British Conservative Party.
 * July 28 - U.S. President Lyndon B. Johnson announces his order to increase the number of United States troops in South Vietnam from 75,000 to 125,000, and to more than double the number of men drafted per month - from 17,000 to 35,000.
 * July 30 - U.S. President Lyndon B. Johnson signs the Social Security Act of 1965 into law, establishing Medicare and Medicaid.

August

 * August 4 - The Cook Islands becomes a free New Zealand-associated state, with its own constitution.
 * August 6 - U.S. President Lyndon B. Johnson signs the Voting Rights Act of 1965 into law, outlawing literacy tests and other discriminatory voting practices.
 * August 9 - Singapore leaves Malaysia.
 * August 11 - The Watts Riots begin in Los Angeles, ending on the 16th after resulting in 34 deaths and over 3,000 arrests.
 * August 18 - Vietnam War – Operation Starlite: 5,500 United States Marines destroy a Viet Cong stronghold on the Van Tuong peninsula in Quảng Ngãi Province, in the first major American ground battle of the war.
 * August 19 - At the conclusion of the Frankfurt Auschwitz trials, 66 ex-SS personnel receive life sentences, 15 others smaller ones.
 * August 20 - Jonathan Myrick Daniels, an Episcopal seminarian from Keene, New Hampshire, is murdered in Hayneville, Alabama, while working in the civil rights movement.
 * August 31 - President Johnson signs a law penalizing the burning of draft cards with up to 5 years in prison and a $1,000 fine.

September

 * September 2 - Pakistani troops enter the Indian sector of Kashmir, while Indian troops try to invade Lahore.
 * September 9 - U.N. Secretary General U Thant negotiates with Pakistan President Ayub Khan.
 * September 9 - U Thant recommends China for United Nations membership.
 * September 9 - The United States Department of Housing and Urban Development is established.
 * September 14 - The fourth and final period of the Second Vatican Council opens.
 * September 16 - China protests against Indian provocations in its border region.
 * September 16 - In Iraq, Prime Minister Arif Abd ar-Razzaq's attempted coup fails.
 * September 17 - King Constantine II of Greece forms a new government with Prime Minister Stephanos Stephanopoulos, in an attempt to end a 2-year-old political crisis.
 * September 18 - Soviet Premier Alexei Kosygin invites the leaders of India and Pakistan to meet in the Soviet Union to negotiate.
 * September 19 - Pakistani Forces achieve a decisive victory at the Battle of Chawinda, ultimately halting the Indian advance and successfully stabilizing the Sialkot Front.
 * September 21 - Gambia, Maldives and Singapore are admitted as members of the United Nations.
 * September 24 - The British governor of Aden cancels the constitution and takes direct control of the protectorate, due to the bad security situation.
 * September 28 - Fidel Castro announces that anyone who wants to can emigrate to the United States.
 * September 30 - The Indonesian army, led by General Suharto, crushes an alleged communist coup attempt (see Transition to the New Order and 30 September Movement).

October

 * October 3 - Fidel Castro announces that Che Guevara has resigned and left the country.
 * October 3 - U.S. President Lyndon B. Johnson signs the Immigration and Nationality Act of 1965 which ends quotas based on national origin.
 * October 4 - Prime minister Ian Smith of Rhodesia and Arthur Bottomley of the Commonwealth of Nations begin negotiations in London.
 * October 5 - Pakistan severs diplomatic relations with Malaysia because of disagreement in the UN.
 * October 8 - Indonesian mass killings of 1965–1966: The Indonesian army instigates the arrest and execution of communists which last until next March.
 * October 9 - A brigade of South Korean soldiers arrive in South Vietnam.
 * October 12 - The U.N. recommends that the United Kingdom try everything to stop a rebellion in Rhodesia.
 * October 12 - Per Borten replaces Einar Gerhardsen as prime minister of Norway.
 * October 13 - Congo President Joseph Kasavubu fires Prime Minister Moise Tshombe and forms a provisional government, with Évariste Kimba in a leading position.
 * October 15 - Vietnam War: The Catholic Worker Movement stages an anti-war protest in Manhattan. One draft card burner is arrested, the first under the new law.
 * October 16 - Anti-war protests draw 100,000 in 80 U.S. cities and around the world
 * October 18 - The Indonesian government outlaws the Communist Party of Indonesia.
 * October 20 - Ludwig Erhard is re-elected Chancellor of West Germany (he had first been elected in 1963).
 * October 21 - The Organization of African Unity meets in Accra, Ghana.
 * October 22 - African countries demand that the United Kingdom use force to prevent Rhodesia from declaring unilateral independence.
 * October 22 - Colonel Christophe Soglo stages a second coup in Dahomey.
 * October 24 - British Prime Minister Harold Wilson and Commonwealth Secretary Arthur Bottomley travel to Rhodesia for negotiations.
 * October 25 - The Soviet Union declares its support of African countries in case Rhodesia unilaterally declares independence.
 * October 26 - Anti-government demonstrations occur in the Dominican Republic.
 * October 27 - Süleyman Demirel of AP forms the new government of Turkey (30th government).
 * October 27 - Brazilian president Humberto de Alencar Castelo Branco removes power from parliament, legal courts and all opposition parties.
 * October 28 - French Foreign Minister Maurice Couve de Murville travels to Moscow.
 * October 28 - Mehdi Ben Barka, a Moroccan politician, is kidnapped in Paris and never seen again
 * October 28 - Pope Paul VI promulgates Nostra aetate, a "Declaration on the Relation of the (Roman Catholic) Church with Non-Christian Religions" by the Second Vatican Council which includes a statement that Jews are not collectively responsible for the death of Jesus.
 * October 30 - In Washington, D.C., a pro-Vietnam War march draws 25,000.

November

 * November 2 - Republican John Vliet Lindsay is elected mayor of New York City.
 * November 2 - Quaker Norman Morrison, 32, sets himself on fire in front of The Pentagon; he dies of his injuries.
 * November 3 - French President Charles de Gaulle announces (just short of his 75th birthday) that he will stand for re-election.
 * November 5 - Martial law is announced in Rhodesia. The United Nations General Assembly accepts British intent to use force against Rhodesia if necessary by a vote of 82–9.
 * November 8 - Vietnam War – Operation Hump: The United States Army 173rd Airborne is ambushed by over 1,200 Viet Cong
 * November 8 - The British Indian Ocean Territory is created, consisting of Chagos Archipelago, Aldabra, Farquhar and Desroches islands.
 * November 8 - The Murder (Abolition of Death Penalty) Act 1965 is given Royal Assent, suspending the death penalty for murder in the United Kingdom.
 * November 9 -In New York City, 22-year-old Catholic Worker Movement member Roger Allen LaPorte sets himself on fire in front of the United Nations building in protest against the Vietnam War.
 * November 11 - In Rhodesia (modern-day Zimbabwe), the white-minority government of Ian Smith unilaterally declares de facto independence
 * November 12 - A UN Security Council resolution (voted 10–0) recommends that other countries not recognize independent Rhodesia.
 * November 14 - Battle of Ia Drang: In the Ia Drang Valley of the Central Highlands in Vietnam, the first major engagement of the war between regular United States and North Vietnamese forces begins.
 * November 20 - The United Nations Security Council recommends that all states stop trading with Rhodesia.
 * November 22 - The United Nations Development Programme (UNDP) is established as a specialized agency of the United Nations.
 * November 23 - Soviet general Mikhail Kazakov assumes command of the Warsaw Pact.
 * November 24 - Congolese lieutenant general Mobutu ousts Joseph Kasavubu and declares himself president.
 * November 26 - At the Hammaguir launch facility in the Sahara Desert, France launches a Diamant A rocket with its first satellite, Astérix-1 on board, becoming the third country to enter outer space.
 * November 27 - Tens of thousands of Vietnam War protesters picket the White House, then march on the Washington Monument.
 * November 27 - The Pentagon tells U.S. President Lyndon B. Johnson that if planned major sweep operations to neutralize Viet Cong forces during the next year are to succeed, the number of American troops in Vietnam will have to be increased from 120,000 to 400,000.
 * November 28 - Vietnam War: In response to U.S. President Lyndon B. Johnson's call for "more flags" in Vietnam, Philippines President-elect Ferdinand Marcos announces he will send troops to help fight in South Vietnam.

December

 * December 1 - The Border Security Force is established in India as a special force to guard the borders.
 * December 3 - The first British aid flight arrives in Lusaka; Zambia had asked for British help against Rhodesia.
 * December 3 - Members of the Organization of African Unity decide to sever diplomatic relations with the United Kingdom, unless the British Government ends the rebellion of Rhodesia by mid-December.
 * December 5 - The "Glasnost Meeting" in Moscow becomes the first spontaneous political demonstration, and the first demonstration for civil rights in the Soviet Union
 * December 8 - Rhodesian prime minister Ian Smith warns that Rhodesia will resist a trade embargo by neighboring countries with force.
 * December 8 - The Race Relations Act becomes the first legislation to address racial discrimination in the UK.
 * December 8 - The Second Vatican Council closes.
 * December 15 - The Caribbean Free Trade Association (CARIFTA) is formed.
 * December 15 - Tanzania and Guinea sever diplomatic relations with the United Kingdom.
 * December 17 - The British government begins an oil embargo against Rhodesia; the United States joins the effort.
 * December 20 - The World Food Programme is made a permanent agency of the United Nations.
 * December 21 - The Soviet Union announces that it has shipped rockets to North Vietnam.
 * December 21 - In West Germany, Konrad Adenauer resigns as chairman of the Christian Democratic Party.
 * December 21 - The United Nations adopts the International Convention on the Elimination of All Forms of Racial Discrimination.
 * December 22 - A military coup is launched in Dahomey.
 * December 25 - The Yemeni Nasserist Unionist People's Organisation is founded in Ta'izz.
 * December 28 - Italian Foreign Minister Amintore Fanfani resigns.
 * December 30 - President Kenneth Kaunda of Zambia announces that Zambia and the United Kingdom have agreed on a deadline before which the Rhodesian white government should be ousted.
 * December 30 - Ferdinand Marcos becomes President of the Philippines.
 * December 31 - Emperor Jean-Bédel Bokassa takes power in the Central African Republic.

January 24

 * Winston Churchill, former Prime Minister of the United Kingdom (1940–1945) and (1951–1955).

February 21

 * Malcolm X African-American Muslim minister and human rights activist is assassinated in New York City.

March 11

 * James Reeb, an American Unitarian Universalist minister, pastor, and activist during the civil rights movement. While participating in the Selma to Montgomery marches he was murdered by white segregationists.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: 1965 in politics


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Urease

Ureases, functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-containing metalloenzymes of high molecular weight.

These enzymes catalyze the hydrolysis of urea into carbon dioxide and ammonia:
 * (NH2)2CO + H2O $urease →$ CO2 + 2NH3

The hydrolysis of urea occurs in two stages. In the first stage, ammonia and carbamic acid are produced. The carbamate spontaneously and rapidly hydrolyzes to ammonia and carbonic acid. Urease activity increases the pH of its environment as ammonia is produced, which is basic.

History
Its activity was first identified in 1876 by Frédéric Alphonse Musculus as a soluble ferment. In 1926, James B. Sumner, showed that urease is a protein by examining its crystallized form. Sumner's work was the first demonstration that a protein can function as an enzyme and led eventually to the recognition that most enzymes are in fact proteins. Urease was the first enzyme crystallized. For this work, Sumner was awarded the Nobel prize in chemistry in 1946. The crystal structure of urease was first solved by P. A. Karplus in 1995.

Structure
A 1984 study focusing on urease from jack bean found that the active site contains a pair of nickel centers. In vitro activation also has been achieved with manganese and cobalt in place of nickel. Lead salts are inhibiting.

The molecular weight is either 480 kDa or 545 kDa for jack-bean urease (calculated mass from the amino acid sequence). 840 amino acids per molecule, of which 90 are cysteine residues.

The optimum pH is 7.4 and optimum temperature is 60 °C. Substrates include urea and hydroxyurea.

Bacterial ureases are composed of three distinct subunits, one large catalytic (α 60–76kDa) and two small (β 8–21 kDa, γ 6–14 kDa) commonly forming (αβγ)3 trimers stoichiometry with a 2-fold symmetric structure (note that the image above gives the structure of the asymmetric unit, one-third of the true biological assembly), they are cysteine-rich enzymes, resulting in the enzyme molar masses between 190 and 300kDa.

An exceptional urease is obtained from Helicobacter sp.. These are composed of two subunits, α(26–31 kDa)-β(61–66 kDa). These subunits form a supramolecular (αβ)12 dodecameric complex. of repeating α-β subunits, each coupled pair of subunits has an active site, for a total of 12 active sites. It plays an essential function for survival, neutralizing gastric acid by allowing urea to enter into periplasm via a proton-gated urea channel. The presence of urease is used in the diagnosis of Helicobacter species.

All bacterial ureases are solely cytoplasmic, except for those in Helicobacter pylori, which along with its cytoplasmic activity, has external activity with host cells. In contrast, all plant ureases are cytoplasmic.

Fungal and plant ureases are made up of identical subunits (~90 kDa each), most commonly assembled as trimers and hexamers. For example, jack bean urease has two structural and one catalytic subunit. The α subunit contains the active site, it is composed of 840 amino acids per molecule (90 cysteines), its molecular mass without Ni(II) ions amounting to 90.77 kDa. The mass of the hexamer with the 12 nickel ions is 545.34 kDa. Other examples of homohexameric structures of plant ureases are those of soybean, pigeon pea and cotton seeds enzymes.

It is important to note, that although composed of different types of subunits, ureases from different sources extending from bacteria to plants and fungi exhibit high homology of amino acid sequences. The single plant urease chain is equivalent to a fused γ-β-α organization. The Helicobacter "α" is equivalent to a fusion of the normal bacterial γ-β subunits, while its "β" subunit is equivalent to the normal bacterial α. The three-chain organization is likely ancestral.

Activity
The kcat/Km of urease in the processing of urea is 1014 times greater than the rate of the uncatalyzed elimination reaction of urea. There are many reasons for this observation in nature. The proximity of urea to active groups in the active site along with the correct orientation of urea allow hydrolysis to occur rapidly. Urea alone is very stable due to the resonance forms it can adopt. The stability of urea is understood to be due to its resonance energy, which has been estimated at 30–40 kcal/mol. This is because the zwitterionic resonance forms all donate electrons to the carbonyl carbon making it less of an electrophile making it less reactive to nucleophilic attack.

Active site
The active site of ureases is located in the α (alpha) subunits. It is a bis-μ-hydroxo dimeric nickel center, with an interatomic distance of ~3.5 Å. > The Ni(II) pair are weakly antiferromagnetically coupled. X-ray absorption spectroscopy (XAS) studies of Canavalia ensiformis (jack bean), Klebsiella aerogenes  and Sporosarcina pasteurii (formerly known as Bacillus pasteurii) confirm 5–6 coordinate nickel ions with exclusively O/N ligation, including two imidazole ligands per nickel. Urea substrate is proposed to displace aquo ligands.

Water molecules located towards the opening of the active site form a tetrahedral cluster that fills the cavity site through hydrogen bonds. Some amino acid residues are proposed to form mobile flap of the site, which gate for the substrate. Cysteine residues are common in the flap region of the enzymes, which have been determined not to be essential in catalysis, although involved in positioning other key residues in the active site appropriately. In Sporosarcina pasteurii urease, the flap was found in the open conformation, while its closed conformation is apparently needed for the reaction.

When compared, the α subunits of Helicobacter pylori urease and other bacterial ureases align with the jack bean ureases.

The binding of urea to the active site of urease has not been observed.

Blakeley/Zerner
One mechanism for the catalysis of this reaction by urease was proposed by Blakely and Zerner. It begins with a nucleophilic attack by the carbonyl oxygen of the urea molecule onto the 5-coordinate Ni (Ni-1). A weakly coordinated water ligand is displaced in its place. A lone pair of electrons from one of the nitrogen atoms on the Urea molecule creates a double bond with the central carbon, and the resulting NH2− of the coordinated substrate interacts with a nearby positively charged group. Blakeley and Zerner proposed this nearby group to be a Carboxylate ion, although deprotonated carboxylates are negatively charged.

A hydroxide ligand on the six coordinate Ni is deprotonated by a base. The carbonyl carbon is subsequently attacked by the electronegative oxygen. A pair of electrons from the nitrogen-carbon double bond returns to the nitrogen and neutralizes the charge on it, while the now 4-coordinate carbon assumes an intermediate tetrahedral orientation.

The breakdown of this intermediate is then helped by a sulfhydryl group of a cysteine located near the active site. A hydrogen bonds to one of the nitrogen atoms, breaking its bond with carbon, and releasing an molecule. Simultaneously, the bond between the oxygen and the 6-coordinate nickel is broken. This leaves a carbamate ion coordinated to the 5-coordinate Ni, which is then displaced by a water molecule, regenerating the enzyme.

The carbamate produced then spontaneously degrades to produce another ammonia and carbonic acid.

Hausinger/Karplus
The mechanism proposed by Hausinger and Karplus attempts to revise some of the issues apparent in the Blakely and Zerner pathway, and focuses on the positions of the side chains making up the urea-binding pocket. From the crystal structures from K. aerogenes urease, it was argued that the general base used in the Blakely mechanism, His320, was too far away from the Ni2-bound water to deprotonate in order to form the attacking hydroxide moiety. In addition, the general acidic ligand required to protonate the urea nitrogen was not identified. Hausinger and Karplus suggests a reverse protonation scheme, where a protonated form of the His320 ligand plays the role of the general acid and the Ni2-bound water is already in the deprotonated state. The mechanism follows the same path, with the general base omitted (as there is no more need for it) and His320 donating its proton to form the ammonia molecule, which is then released from the enzyme. While the majority of the His320 ligands and bound water will not be in their active forms (protonated and deprotonated, respectively,) it was calculated that approximately 0.3% of total urease enzyme would be active at any one time. While logically, this would imply that the enzyme is not very efficient, contrary to established knowledge, usage of the reverse protonation scheme provides an advantage in increased reactivity for the active form, balancing out the disadvantage. Placing the His320 ligand as an essential component in the mechanism also takes into account the mobile flap region of the enzyme. As this histidine ligand is part of the mobile flap, binding of the urea substrate for catalysis closes this flap over the active site and with the addition of the hydrogen bonding pattern to urea from other ligands in the pocket, speaks to the selectivity of the urease enzyme for urea.

Ciurli/Mangani
The mechanism proposed by Ciurli and Mangani is one of the more recent and currently accepted views of the mechanism of urease and is based primarily on the different roles of the two nickel ions in the active site. One of which binds and activates urea, the other nickel ion binds and activates the nucleophilic water molecule. With regards to this proposal, urea enters the active site cavity when the mobile ‘flap’ (which allows for the entrance of urea into the active site) is open. Stability of the binding of urea to the active site is achieved via a hydrogen-bonding network, orienting the substrate into the catalytic cavity. Urea binds to the five-coordinated nickel (Ni1) with the carbonyl oxygen atom. It approaches the six-coordinated nickel (Ni2) with one of its amino groups and subsequently bridges the two nickel centers. The binding of the urea carbonyl oxygen atom to Ni1 is stabilized through the protonation state of Hisα222 Nԑ. Additionally, the conformational change from the open to closed state of the mobile flap generates a rearrangement of Alaα222 carbonyl group in such a way that its oxygen atom points to Ni2. The Alaα170 and Alaα366 are now oriented in a way that their carbonyl groups act as hydrogen-bond acceptors towards NH2 group of urea, thus aiding its binding to Ni2. Urea is a very poor chelating ligand due to low Lewis base character of its NH2 groups. However the carbonyl oxygens of Alaα170 and Alaα366 enhance the basicity of the NH2 groups and allow for binding to Ni2. Therefore, in this proposed mechanism, the positioning of urea in the active site is induced by the structural features of the active site residues which are positioned to act as hydrogen-bond donors in the vicinity of Ni1 and as acceptors in the vicinity of Ni2. The main structural difference between the Ciurli/Mangani mechanism and the other two is that it incorporates a nitrogen, oxygen bridging urea that is attacked by a bridging hydroxide.

Action in pathogenesis
Bacterial ureases are often the mode of pathogenesis for many medical conditions. They are associated with hepatic encephalopathy / Hepatic coma, infection stones, and peptic ulceration.

Infection stones
Infection induced urinary stones are a mixture of struvite (MgNH4PO4•6H2O) and carbonate apatite [Ca10(PO4)6•CO3]. These polyvalent ions are soluble but become insoluble when ammonia is produced from microbial urease during urea hydrolysis, as this increases the surrounding environments pH from roughly 6.5 to 9. The resultant alkalinization results in stone crystallization. In humans the microbial urease, Proteus mirabilis, is the most common in infection induced urinary stones.

Urease in hepatic encephalopathy / hepatic coma
Studies have shown that Helicobacter pylori along with cirrhosis of the liver cause hepatic encephalopathy and hepatic coma. Helicobacter pylori release microbial ureases into the stomach. The urease hydrolyzes urea to produce ammonia and carbonic acid. As the bacteria are localized to the stomach ammonia produced is readily taken up by the circulatory system from the gastric lumen. This results in elevated ammonia levels in the blood, a condition known as hyperammonemia; eradication of Helicobacter pylori show marked decreases in ammonia levels.

Urease in peptic ulcers
Helicobacter pylori is also the cause of peptic ulcers with its manifestation in 55–68% reported cases. This was confirmed by decreased ulcer bleeding and ulcer reoccurrence after eradication of the pathogen. In the stomach there is an increase in pH of the mucosal lining as a result of urea hydrolysis, which prevents movement of hydrogen ions between gastric glands and gastric lumen. In addition, the high ammonia concentrations have an effect on intercellular tight junctions increasing permeability and also disrupting the gastric mucous membrane of the stomach.

Occurrence and applications in agriculture
Urea is found naturally in the environment and is also artificially introduced, comprising more than half of all synthetic nitrogen fertilizers used globally. Heavy use of urea is thought to promote eutrophication, despite the observation that urea is rapidly transformed by microbial ureases, and thus usually does not persist. Environmental urease activity is often measured as an indicator of the health of microbial communities. In the absence of plants, urease activity in soil is generally attributed to heterotrophic microorganisms, although it has been demonstrated that some chemoautotrophic ammonium oxidizing bacteria are capable of growth on urea as a sole source of carbon, nitrogen, and energy.

Inhibition in fertilizers
The inhibition of urease is a significant goal in agriculture because the rapid breakdown of urea-based fertilizers is wasteful and environmentally damaging. Phenyl phosphorodiamidate and N-(n-butyl)thiophosphoric triamide are two such inhibitors.

Biomineralization
By promoting the formation of calcium carbonate, ureases are potentially useful for biomineralization-inspired processes. Notably, microbiologically induced formation of calcium carbonate can be used in making bioconcrete.

Non-enzymatic action
In addition to acting as an enzyme, some ureases (especially plant ones) have additional effects that persist even when the catalytic function is disabled. These include entomotoxicity, inhibition of fungi, neurotoxicity in mammals, promotion of endocytosis and inflammatory eicosanoid production in mammals, and induction of chemotaxis in bacteria. These activities may be part of a defense mechanism.

Urease insect-toxicity was originally noted in canatoxin, an orthologous isoform of jack bean urease. Digestion of the peptide identified a 10-kDa portion most responsible for this effect, termed jaburetox. An analogous portion from the soybean urease is named soyuretox. Studies on insects show that the entire protein is toxic without needing any digestion, however. Nevertheless, the "uretox" peptides, being more concentrated in toxicity, show promise as biopesticides.

As diagnostic test
Many gastrointestinal or urinary tract pathogens produce urease, enabling the detection of urease to be used as a diagnostic to detect presence of pathogens.

Urease-positive pathogens include:
 * Proteus mirabilis and Proteus vulgaris
 * Ureaplasma urealyticum, a relative of Mycoplasma spp.
 * Nocardia
 * Corynebacterium urealyticum
 * Cryptococcus spp., an opportunistic fungus
 * Helicobacter pylori
 * Certain Enteric bacteria including Proteus spp., Klebsiella spp., Morganella, Providencia, and possibly Serratia spp.
 * Brucella
 * Staphylococcus saprophyticus
 * Staphylococcus aureus

Inhibitors
A wide range of urease inhibitors of different structural families are known. Inhibition of urease is not only of interest to agriculture, but also to medicine as pathogens like H. pylori produce urease as a survival mechanism. Known structural classes of inhibitors include:

 * Analogues of urea, the strongest being thioureas like 1-(4-chlorophenyl)-3-palmitoylthiourea.
 * Phosphoramidates, the most commonly used in agriculture (see above).
 * Hydroquinone and quinones. In medicine, the most interesting are quinolones, already a class of widely used antibiotics.
 * Some plant metabolites are also urease inhibitors, an example being allicin. These have potential both as environmentally-friendly fertilizer additives and natural drugs.

Extraction
First isolated as a crystal in 1926 by Sumner, using acetone solvation and centrifuging. Modern biochemistry has increased its demand for urease. Jack bean meal, watermelon seeds, and pea seeds have all proven useful sources of urease.

title: Urease


text:
Gauche (Scheme implementation)

Gauche is an R7RS Scheme implementation. It is designed for scripting in a production environment. It is intended to allow programmers and system administrators to write scripts in support of daily operations. Quick startup, built-in system interface, native multilingual support are some of its key design goals.

Gauche is free software under the BSD License. It is primarily developed by Shiro Kawai.

Features

 * Quick startup - Gauche includes common features in its executable, while less common functions are in libraries which are loaded on demand.
 * Module system - A simple module system, API compatible to STklos.
 * Object system - CLOS-like object system with metaobject protocol. Almost API compatible to STklos. It is also similar to Guile's object system.
 * Native multilingual support - Strings are represented by multibyte string internally. You can use UTF-8, EUC-JP, Shift-JIS or no multibyte encoding. Conversion between native coding system and external coding system is supported by port objects.
 * Multibyte regexp - Regular expression matcher is aware of multibyte string; you can use multibyte characters both in patterns and matched strings.
 * Built-in system interface - Gauche has built-in support for most POSIX.1 system calls.
 * Network interface - Has API for socket-based network interface, including IPv6 if the OS supports it.
 * Multithreading - Multithreading is supported on top of pthreads. Scheme-level API conforms to SRFI-18.
 * DBM interface - Interfaces to dbm, ndbm and/or gdbm.
 * XML parsing - Oleg Kiselyov's SXML tools are included.

title: Gauche (Scheme implementation)


text:
Talk:Stop Esso campaign

Untitled
Could someone write abit about Esso's legal action against the stop esso campaign in luxembourg and france.

Hey, If you put back in thoese sentences about the legeal battle.. please make them factually accurate this time, and written from a view point that is more netural, it's obvious from the old viewpoint it was anti-corporate. You semi-made me angry by reverting the states/claims thing... you know that state is a pov, claims is valid. thanks 203.112.19.195 14:19, 10 Oct 2004 (UTC)
 * They are factually accurate, and I've replaced them. Not only did you delete them, you also deleted a link to the Guardian article which verified the facts. Please, if you have a problem with any of these facts, describe your problem. Rhobite 00:20, Oct 11, 2004 (UTC)
 * Actually 203.whatever, if you had stopped to look at my final revision you will observe that I did indeed replace states with claims which is entirely apposite; the evidence is there in the revision history, but since you need facts spelt out large for you, the link to it is: . Simply trying to pretend that this stuff isn't happening by blanking it doesn't change the facts in the matter. Sjc 10:27, 11 Oct 2004 (UTC)

"denying the existence of global warming" I thought that Esso's stance was that global warming was a real effect, but that there is (in their opinion) insufficient evidence that the effect is man-made. Having this view is not actually a crime. Or maybe these days having any view that doesn't coincide with unqualified talentless "greenies" is a crime.

Esso or Exxon?
The article uses both names. I think it would be better and more understandable if only one name were used in reference to the company. After all one of the titles is Exxon's reaction to Stop Esso campaign, but it only refers to Esso in the text in that section.Fryd1e 20:06, 17 June 2006 (UTC)

Requested page move
A request has been made to move Stop Esso campaign → Stop E$o campaign - That's the spelling they use in their campaign and they were even sued for spelling it that way - See Stop Esso campaign -Hyad 04:33, August 8, 2005 (UTC)

 * Oppose. Per Manual of Style (trademarks), we don't spell things with fancy symbols for letters, though it is okay to note that usage within the article itself.  Dragons flight 23:51, August 8, 2005 (UTC)

It was requested that this article be renamed but there was no consensus for it be moved. violet/riga (t) 12:57, 18 August 2005 (UTC)

Criticism as original research?
I wonder if the criticism in this article is an original research. If that research turns out to be true, then more people should convert to bicycling, but even bikes use lubricating oil.--Jusjih 16:07, 30 January 2007 (UTC)

Fair use rationale for Image:Exxtreme Droughts.jpg
Image:Exxtreme Droughts.jpg is being used on this article. I notice the image page specifies that the image is being used under fair use but there is no explanation or rationale as to why its use in this Wikipedia article constitutes fair use. In addition to the boilerplate fair use template, you must also write out on the image description page a specific explanation or rationale for why using this image in each article is consistent with fair use.

Please go to the image description page and edit it to include a fair use rationale. Using one of the templates at Fair use rationale guideline is an easy way to insure that your image is in compliance with Wikipedia policy, but remember that you must complete the template. Do not simply insert a blank template on an image page.

If there is other fair use media, consider checking that you have specified the fair use rationale on the other images used on this page. Note that any fair use images uploaded after 4 May, 2006, and lacking such an explanation will be deleted one week after they have been uploaded, as described on criteria for speedy deletion. If you have any questions please ask them at the Media copyright questions page. Thank you.

BetacommandBot 05:48, 1 October 2007 (UTC)

External links modified
Hello fellow Wikipedians,

I have just added archive links to 2 one external links on Stop Esso campaign. Please take a moment to review my edit. If necessary, add after the link to keep me from modifying it. Alternatively, you can add to keep me off the page altogether. I made the following changes:
 * Added archive http://web.archive.org/web/20070101200541/http://www.stopesso.com:80/ to http://www.stopesso.com
 * Added archive http://web.archive.org/web/20041012084612/http://www.greenpeace.fr:80/stopesso/ to http://www.greenpeace.fr/stopesso/

When you have finished reviewing my changes, please set the checked parameter below to true to let others know.

Cheers.—cyberbot II  Talk to my owner :Online 23:10, 27 February 2016 (UTC)

title: Talk:Stop Esso campaign


text:
User talk:GrandVoivodOfErdely

ﷲ ﷶ ﷺ ﷴ ,ﷳ ﷲ

from wikibrig's talk page: A modest example begins in the realm of Seinfeld. Connotations regarding the suggested syntax are only meant to be instructive about the concept itself, and may be articulated ideally by using it. Elain

Vandelay

Van_Nostrand

Pennypecker

(For reasons perhaps only known to the author(s).)

(unknown)

Baseball

Cal Ripken, Jr.

Cal_Varnsen

inspired

not Karl_Varnsen

Convertible ...

It's a Turbo?!

Perhaps, if the Wikibriq concept were allowed to manifest itself, unremarkable constructions such as

(For reasons perhaps only known to the author(s))

or

may be avoided.

Frank W ~@) R, Jan. 7th, 19:27 (PST). ~ GrandVoivodOfErdely GrandVoivodOfErdely 22:43 Jan 14, 2003 (UTC)

---

Hello. Any reason why you're quoting Fwappler's comments on Seinfeld? BTW, if you're making many edits to your user pages, please could you mark the "minor edit" box. tx -- Tarquin 22:46 Jan 14, 2003 (UTC) --- after my brief experimentation with fwappler's experimentation, nothing makes much sense. Can the original author please enlighten me?

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Fwappler is a relatively new contributor. Most people here have no idea what s/he means most of the time. It's rather confusing. -- Tarquin 23:17 Jan 14, 2003 (UTC)

Please don't post copyrighted articles. It can cause the entire project to be shut down. -- Zoe

Hi. what does what you've written on Talk:Ferdosi mean? -- Tarquin 00:58 Mar 9, 2003 (UTC)

Are you planning on making any contributions to Talk pages, or are you just adding gibberish? -- Zoe

Zoe, it's actually not gibberish, I resent you calling it as such. It spells out to be "allah", ofcourse in arabic. Grand Voivod has also done the same to my talk page, yet User:k1 seems to have deleted it. Grand, as a Muslim I am not at all dissapointed of what you did to my user page, but I am not sure if others are as apreciative ;). Yet for some odd reason I could not make out all the letters! Yours Truly

I am the User:k1 that you mention above. You are absolutely wrong in saying that I have deleted the gibberish that that guy put on Talk:Ferdosi page or anywhere else. Fortunately, the history of changes of all pages can be viewed and you can determine who did what, when. I did, however, resent what that bozo did, and upon a little investigation, I noticed that he had done the same stupid thing on a number of other pages, all of which were out of place and uncalled-for. But it seems that he later deleted them himself. I don't care that what he put there says "Allah" in Arabic; so what? What place does that have on Talk:Ferdosi page? What if Christians start putting "Jesus" all over the place? It was gibberish. Keyvan

What on earth are you doing GRAND? What are the targets you posted on discussion pages for? I appologize, Grand is not planning on making contributions he just likes posting gibberish. The U.K must have a very awful Privy Council to consider you as an advisor. Alireza Hashemi

---

Would you mind saying what are the reasons for your changes when you do them? jbc Sat May 24 08:00:01 UTC 2003

For obvious reasons!  ﷲ ﷶ ﷺ ﷴ ,ﷳ ﷲ

title: User talk:GrandVoivodOfErdely


text:
Primary election

Party primaries or primary elections are elections where a political party selects a candidate for an upcoming general election. Depending on the country and administrative division, voters may consist of all voters in an open primary, or solely the members of a political party in what is called a closed primary. In addition to these, there are other variants on primaries (which are discussed below) that are used by many countries holding elections throughout the world.

The origins of primary elections can be traced to the progressive movement in the United States, which aimed to take the power of candidate nomination from party leaders to the people. However, political parties control the method of nomination of candidates for office in the name of the party. Other methods of selecting candidates include caucuses, internal selection by a party body such as a convention or party congress, direct nomination by the party leader, and nomination meetings.

Parties in countries using the parliamentary system sometimes have an equivalent process, a leadership election, where party members elect the leader of their political party. A party's leader will typically become the head of government should their party win a majority of seats. Thus, a leadership election is also often considered to be one for the party's de facto candidate for prime minister or premier just like a primary.

However, Prime Ministerial primaries have been held in inter-party electoral alliances, such as the 2021 Hungarian opposition primary, and also in cases where a single party opted to retain its leader but select someone else as its Prime Ministerial candidate, as the Portuguese Socialist Party has done in 2014.

The inverse may also happen; the Democratic Progressive Party in Taiwan automatically bestows the party's internal leadership on a sitting DPP president.

General
Where primary elections are organized by parties, not the administration, two types of primaries can generally be distinguished:

 * Closed primary. (synonyms: internal primaries, party primaries) In the case of closed primaries, internal primaries, or party primaries, only party members can vote.
 * Open primary. All voters can take part in an open primary and may cast votes on a ballot of any party. The party may require them to express their support to the party's values and pay a small contribution to the costs of the primary.

In the United States, further types can be differentiated:

Closed primary

 * People may vote in a party's primary only if they are registered members of that party prior to election day. Independents cannot participate. Because some political parties name themselves independent, the terms "non-partisan" or "unaffiliated" often replace "independent" when referring to those who are not affiliated with a political party. As of 2016, thirteen states and the District of Columbia used closed primaries.

Semi-closed or semi-open

 * As in closed primaries, registered party members can vote only in their own party's primary. Semi-closed systems, however, allow unaffiliated voters to choose a party to participate in as well. Depending on the state, independents either make their choice of party primary privately, inside the voting booth, or publicly, by registering with any party on Election Day.
 * Sixteen states – Alaska, Arizona, California, Colorado, Illinois, Iowa, Kansas, Maine, New Hampshire, New Jersey, North Carolina, Ohio, Oregon, Rhode Island, Utah, and West Virginia – have semi-closed primaries that allow voters to register or change party preference on election day. Massachusetts allows unenrolled voters or members of minor parties to vote in the primary of either major party, but registration or party changes must be done no fewer than 20 days prior to the primary.

Open primary

 * A registered voter may vote in any party primary regardless of his or her own party affiliation. Fourteen states – Alabama, Arkansas, Georgia, Hawaii, Michigan, Minnesota, Missouri, Montana, North Dakota, South Carolina, Texas, Vermont, Virginia, and Wisconsin – have open primaries.
 * This system is sometimes criticized for increasing the ease with which voters can engage in party raiding. Raiding consists of voters of one party crossing over and voting in the primary of another party, effectively allowing a party to choose a weak opponent in the election. An example of this can be seen in the 1998 Vermont senatorial primary with the nomination of Fred Tuttle as the Republican candidate in the general election.

Blanket primary

 * A primary where voters do not have to select one specific political party for which the ballot is not restricted to candidates from one party, and where the top candidate from each party advances to the general election.

Nonpartisan blanket primary or Two-round system
Unified primary
 * Technically not a primary, as the term "nonpartisan primary" is an oxymoron. Instead, the election would correctly be called the first round of a two-round system. The top two candidates advance to the general election regardless of party affiliation.
 * Louisiana has famously operated under this system, which has been nicknamed the "jungle primary", since the 1980s.
 * California has used a nonpartisan blanket primary since 2012 after passing Proposition 14 in 2010.
 * Washington has used a nonpartisan blanket primary since 2008.
 * Unlike the kinds of primaries mentioned above, St. Louis uses a nonpartisan primary with approval voting, where voters may support any number of candidates instead of one.

In the United States
The United States is one of a handful of countries to select candidates through popular vote in a primary election system; most other countries rely on party leaders or party members to select candidates, as was previously the case in the U.S.

The selection of candidates for federal, state, and local general elections takes place in primary elections organized by the public administration for the general voting public to participate in for the purpose of nominating the respective parties' official candidates; state voters start the electoral process for governors and legislators through the primary process, as well as for many local officials from city councilors to county commissioners. The candidate who moves from the primary to be successful in the general election takes public office.

In modern politics, primary elections have been described as a vehicle for transferring decision-making from political insiders to voters, though political science research indicates that the formal party organizations retain significant influence over nomination outcomes.

History
The direct primary became important in the United States at the state level starting in the 1890s and at the local level in the 1900s. The first primary elections came in the Democratic Party in the South in the 1890s starting in Louisiana in 1892. By 1897 the Democratic party held primaries to select candidates in 11 Southern and border states. Unlike the final election run by government officials, primaries were run by party officials rather than being considered official elections, allowing them to exclude African American voters. The US Supreme Court would later declare such white primaries unconstitutional in Smith v. Allwright in 1944.

The direct primary was promoted primarily by regular party leaders as a way to promote party loyalty. Progressive reformers like Robert M. La Follette of Wisconsin also campaigned for primaries, leading Wisconsin to approve them in a 1904 referendum.

Despite this, presidential nominations depended chiefly on party conventions until 1972. In 1968, Hubert Humphrey won the Democratic nomination without entering any of the 14 state primaries, causing substantial controversy at the national convention. To prevent a recurrence, Democrats set up the McGovern–Fraser Commission which required all states to primaries, and the Republican party soon followed suit.

Non-partisan
Primaries can be used in nonpartisan elections to reduce the set of candidates that go on to the general election (qualifying primary). (In the U.S., many city, county and school board elections are non-partisan, although often the political affiliations of candidates are commonly known.) In some states and localities, candidates receiving more than 50% of the vote in the primary are automatically elected, without having to run again in the general election. In other states, the primary can narrow the number of candidates advancing to the general election to the top two, while in other states and localities, twice as many candidates as can win in the general election may advance from the primary.

Blanket
When a qualifying primary is applied to a partisan election, it becomes what is generally known as a blanket or Louisiana primary: typically, if no candidate wins a majority in the primary, the two candidates receiving the highest pluralities, regardless of party affiliation, go on to a general election that is in effect a run-off. This often has the effect of eliminating minor parties from the general election, and frequently the general election becomes a single-party election. Unlike a plurality voting system, a run-off system meets the Condorcet loser criterion in that the candidate that ultimately wins would not have been beaten in a two-way race with every one of the other candidates.

Because many Washington residents were disappointed over the loss of their blanket primary, which the Washington State Grange helped institute in 1935, the Grange filed Initiative 872 in 2004 to establish a blanket primary for partisan races, thereby allowing voters to once again cross party lines in the primary election. The two candidates with the most votes then advance to the general election, regardless of their party affiliation. Supporters claimed it would bring back voter choice; opponents said it would exclude third parties and independents from general election ballots, could result in Democratic or Republican-only races in certain districts, and would in fact reduce voter choice. The initiative was put to a public vote in November 2004 and passed. On 15 July 2005, the initiative was found unconstitutional by the U.S. District Court for the Western District of Washington. The U.S. Supreme Court heard the Grange's appeal of the case in October 2007. In March 2009, the Supreme Court upheld the constitutionality of the Grange-sponsored Top 2 primary, citing a lack of compelling evidence to overturn the voter-approved initiative.

In elections using electoral systems where strategic nomination is a concern, primaries can be very important in preventing "clone" candidates that split their constituency's vote because of their similarities. Primaries allow political parties to select and unite behind one candidate. However, tactical voting is sometimes a concern in non-partisan primaries as members of the opposite party can vote for the weaker candidate in order to face an easier general election.

In California, under Proposition 14 (Top Two Candidates Open Primary Act), a voter-approved referendum, in all races except for that for U.S. president and county central committee offices, all candidates running in a primary election regardless of party will appear on a single primary election ballot and voters may vote for any candidate, with the top two vote-getters overall moving on to the general election regardless of party. The effect of this is that it will be possible for two Republicans or two Democrats to compete against each other in a general election if those candidates receive the most primary-election support.

Partisan
As a result of a federal court decision in Idaho, the 2011 Idaho Legislature passed House Bill 351 implementing a closed primary system.

In May 2024, the Republican Party of Texas approved at its bi-annual convention an amendment to its party rules that changes its primary from an open primary to a closed primary, in which only voters registered with the Republican party may now vote in the Republican primary election. State law in Texas currently mandates open primaries, where voters select which primary to vote in when they go to vote rather than affiliating with a party prior to the primary.

Oregon was the first American state in which a binding primary election was conducted entirely via the internet. The election was held by the Independent Party of Oregon in July, 2010.

Presidential primaries
In the United States, Iowa and New Hampshire have drawn attention every four years because they hold the first caucus and primary election, respectively, and often give a candidate the momentum to win their party's nomination. Since 2000, the primary in South Carolina has also become increasingly important, as it is the first Southern state to hold a primary election in the calendar year.

A criticism of the current presidential primary election schedule is that it gives undue weight to the few states with early primaries, as those states often build momentum for leading candidates and rule out trailing candidates long before the rest of the country has even had a chance to weigh in, leaving the last states with virtually no actual input on the process. The counterargument to this criticism, however, is that, by subjecting candidates to the scrutiny of a few early states, the parties can weed out candidates who are unfit for office.

The Democratic National Committee (DNC) proposed a new schedule and a new rule set for the 2008 presidential primary elections. Among the changes: the primary election cycle would start nearly a year earlier than in previous cycles, states from the West and the South would be included in the earlier part of the schedule, and candidates who run in primary elections not held in accordance with the DNC's proposed schedule (as the DNC does not have any direct control over each state's official election schedules) would be penalized by being stripped of delegates won in offending states. The New York Times called the move, "the biggest shift in the way Democrats have nominated their presidential candidates in 30 years."

Of note regarding the DNC's proposed 2008 presidential primary election schedule is that it contrasted with the Republican National Committee's (RNC) rules regarding presidential primary elections. "No presidential primary, caucus, convention, or other meeting may be held for the purpose of voting for a presidential candidate and/or selecting delegates or alternate delegates to the national convention, prior to the first Tuesday of February in the year in which the national convention is held." In, this date is February.

Candidates for U.S. President who seek their party's nomination participate in primary elections run by state governments, or caucuses run by the political parties. Unlike an election where the only participation is casting a ballot, a caucus is a gathering or "meeting of party members designed to select candidates and propose policies". Both primaries and caucuses are used in the presidential nomination process, beginning in January or February and culminating in the late summer political party conventions. Candidates may earn convention delegates from each state primary or caucus. Sitting presidents generally do not face serious competition from their party.

Primary classifications
While it is clear that the closed/semi-closed/semi-open/open classification commonly used by scholars studying primary systems does not fully explain the highly nuanced differences seen from state to state, still, it is very useful and has real-world implications for the electorate, election officials, and the candidates themselves.

As far as the electorate is concerned, the extent of participation allowed to weak partisans and independents depends almost solely on which of the aforementioned categories best describes their state's primary system. Open and semi-open systems favor this type of voter, since they can choose which primary they vote in on a yearly basis under these models. In closed primary systems, true independents are, for all practical purposes, shut out of the process.

This classification further affects the relationship between primary elections and election commissioners and officials. The more open the system, the greater the chance of raiding, or voters voting in the other party's primary in hopes of getting a weaker opponent chosen to run against a strong candidate in the general election. Raiding has proven stressful to the relationships between political parties, who feel cheated by the system, and election officials, who try to make the system run as smoothly as possible.

Perhaps the most dramatic effect this classification system has on the primary process is its influence on the candidates themselves. Whether a system is open or closed dictates the way candidates run their campaigns. In a closed system, from the time a candidate qualifies to the day of the primary, they tend to have to cater to partisans, who tend to lean to the more extreme ends of the ideological spectrum. In the general election, under the assumptions of the median voter theorem, the candidate must move more towards the center in hopes of capturing a plurality.

In Europe
In Europe, primaries are not organized by the public administration but by parties themselves, and legislation is mostly silent on primaries. However, parties may need government cooperation, particularly for open primaries.

Whereas closed primaries are rather common within many European countries, a few political parties in Europe have opted for open primaries. Parties generally organize primaries to nominate the party leader (leadership election). The underlying reason for that is that most European countries are parliamentary democracies. National governments are derived from the majority in the Parliament, which means that the head of the government is generally the leader of the winning party. France is one exception to this rule.

Closed primaries happen in many European countries, while open primaries have so far only occurred in the socialist and social-democratic parties in Greece and Italy, whereas France's Socialist Party organised the first open primary in France in October 2011.

One of the more recent developments is organizing primaries on the European level. European parties that organized primaries so far were the European Green Party (EGP) and the Party of European Socialists (PES)

European Union
With a view to the European elections, many European political parties consider organizing a presidential primary.

Indeed, the Lisbon treaty, which entered into force in December 2009, lays down that the outcome of elections to the European Parliament must be taken into account in selecting the President of the Commission; the Commission is in some respects the executive branch of the EU and so its president can be regarded as the EU prime minister. Parties are therefore encouraged to designate their candidates for President of the European Commission ahead of the next election in 2014, in order to allow voters to vote with a full knowledge of the facts. Various have suggested using primaries to elect these candidates.
 * In April 2004, a former British conservative MEP, Tom Spencer, advocated for American-style primaries in the European People's Party: "A series of primary elections would be held at two-week intervals in February and March 2009. The primaries would start in the five smallest countries and continue every two weeks until the big five voted in late March. To avoid swamping by the parties from the big countries, one could divide the number of votes cast for each candidate in each country by that country's voting weight in the Council of Ministers. Candidates for the post of president would have to declare by 1 January 2009."
 * In July 2013 European Green Party (EGP) announced that it would run a first ever European-wide open primary as the preparation for the European elections in 2014. It was to be open to all citizens of the EU over the age of 16 who "supported green values" They elected two transnational candidates who were to be the face of the common campaign of the European green parties united in the EGP, and who also were their candidates for European Commission president.
 * Following the defeat of the Party of European Socialists during the European elections of June 2009, the PES Congress that took place in Prague in December 2009 made the decision that PES would designate its own candidate before the 2014 European elections. A Campaign for a PES primary was then launched by PES supporters in June 2010, and it managed to convince the PES Council meeting in Warsaw in December 2010 to set up Working Group "Candidate 2014" in charge of proposing a procedure and timetable for a "democratic" and "transparent" designation process "bringing on board all our parties and all levels within the parties".

The European think-tank Notre Europe also suggested European parties should designate candidates for High Representative of the Union for Foreign Affairs.

Finally, the European Parliament envisaged to introduce a requirement for internal democracy in the regulation on the statute of European political parties. European parties would therefore have to involve individual members in the major decisions such as designating the presidential candidate.

Armenia
On 24 and 25 November 2007, the Armenian Revolutionary Federation political party conducted a non-binding Armenia-wide primary election. The party asked the people of their recommendation of who they should nominate as their candidate for the upcoming presidential election.

France
The means by which the candidate of an established political party is selected has evolved. Until 2012, none of the six Presidents elected through direct election faced a competitive internal election.

 * The right didn't hold often primary elections to decide for their national candidates.
 * In 2007, Nicolas Sarkozy, President of the UMP, organized an approval "primary" without any opponent. He won by 98% and made his candidacy speech thereafter.
 * In 2016, The Republicans held, on 20 and 27 November, primaries to decide of their presidential candidate for 2017.
 * On the left, however, the Socialist Party of François Mitterrand has been plagued by internal divisions since the latter departed from politics. Rather than forming a new party, which is the habit on the right-wing, the party started to elect its nominee internally.
 * A first try in 1995: Lionel Jospin won the nomination three months before the election. He lost in the run-off to Jacques Chirac. Later in 2002, although the candidacy of then-PM Jospin was undisputed in his party, each of the five left-wing parties of the government he led sent a candidate, paving the way for all five to lose by the spoiler effect.
 * The idea made progress as the 2007 race approached, once the referendum on a European constitution was over. The latter showed strong ideological divisions within the left-wing spectrum, and the Socialist Party itself. This prevented the possibility of a primary spanning the whole left-wing, that would give its support to a presidential candidate. Given that no majority supported either a leader or a split, a registration campaign, enabling membership for only 20 euros, and a closed primary was organized, which Ségolène Royal won. She qualified to the national run-off that she lost to Nicolas Sarkozy.
 * In 2011, the Socialist Party decided to organise the first ever open primary in France to pick the Socialist party and the Radical Party of the Left nominee for the 2012 presidential election. Inspired by the 2008 U.S. primaries, it was seen as a way to reinvigorate the party. The idea was first proposed by Terra Nova, an independent left-leaning think tank, in a 2008 report. It was also criticized for going against the nature of the regime. The open primary was not state-organized : the party took charge of all the electoral procedures, planning to set up 10,000 voting polls. All citizens on the electoral rolls, members of the Socialist party and the Radical Party of the Left, and members of the parties' youth organisation (MJS and JRG), including minors of 15 to 18 years old, were entitled to vote in exchange for one euro to cover the costs. More than 3 million people participated in this first open primary, which was considered a success, and former party leader François Hollande was designated the Socialist and Radical candidate for the 2012 presidential election.
 * Other parties organize membership primaries to choose their nominee, such as Europe Ecologie – Les Verts (EE-LV) (2006, 2011, 2016), and the French Communist Party in 2011.
 * At the local level, membership primaries are the rule for Socialist Party's candidates, but these are usually not competitive. In order to tame potential feud in his party, and prepare the ground for a long campaign, Sarkozy pushed for a closed primary in 2006 to designate the UMP candidate for the 2008 election of the Mayor of Paris. Françoise de Panafieu was elected in a four-way race. However, she did not clinch the mayorship two years later.

Germany
In Germany, top candidates for the federal election can be selected in primaries. For party leaders, however, the selection at delegate conferences is required by law. It is, nevertheless, possible to hold a non-binding primary.

Top candidates
The Greens nominated their top candidates for the 2013 federal election (election of Jürgen Trittin and Katrin Göring-Eckardt) and for the 2017 federal election (election of Cem Özdemir and Katrin Göring-Eckardt) in a primary election by all party members (closed primary).

Primary elections are used much more frequently by parties at the regional than at the federal level.

Party leaders
The first party to use a (non-binding) closed primary to select its party leader at the federal level was the SPD in 1993. After the surprising resignation of Andrea Nahles, the SPD held another party primary to determine her successor in 2019. A dual leadership of Saskia Esken and Norbert Walter-Borjans was elected. The CDU used the procedure for the first time in 2021. Friedrich Merz prevailed against two competitors Norbert Röttgen and Helge Braun in an online ballot of all CDU party members.

Hungary
A two-round primary election was held in Budapest, Hungary in 2019 between four opposition parties, to select a single candidate to the 2019 Budapest mayoral election. A smaller primary was also held in the district of Ferencváros.

For the 2022 parliamentary elections, the opposition parties organized a primary to select both their candidates for MPs and prime minister.

Italy
Primary election were introduced in Italy to establish the centre-left candidates for 2005 regional election. In that occasion the centre-left The Union coalition held open primaries in order to select candidates for President of Apulia and Calabria. A more politically significant primary was held on 16 October 2005, when The Union asked its voters to decide the candidate for Prime Minister in the 2006 general election: 4,300,000 voters showed up and Romano Prodi won hands down. Two years later, on 14 October 2007, voters of the Democratic Party were called to choose the party leader among a list of six, their representatives to the Constituent Assembly and the local leaders. The primary was a success, involving more than 3,500,000 people across Italy, and gave to the winner Walter Veltroni momentum in a difficult period for the government and the centre-left coalition. The centre-right (see House of Freedoms, The People of Freedom, centre-right coalition and Forza Italia) has never held a primary at the national level, but held some experiments at the very local level.

Russia
The first primaries in the history of Russia were held in May 2000 in St. Petersburg, the local branches of the parties Yabloko and the Union of Right Forces, who before the Gubernatorial election offered citizens to choose a single candidate from the democratic opposition.

In 2007, before the parliamentary elections, United Russia held primaries in several regions. However, its results were not sufficiently taken into account when nominating candidates from the party. For example, the congress of United Russia included in the regional party list in the Samara region not the winners of the primaries, but those who did not even participate in the primaries.

In the same year 2007, A Just Russia held the primaries to determine the candidate for the Gubernatorial election in Altai Krai. Anyone could vote for them, for which special items were opened. However, in the future, A Just Russia did not begin to pursue the primaries.

In 2011, United Russia, together with the All-Russian People's Front, held primaries for the nomination of candidates for the Duma election. This vote was called the "All-People's Primaries", but in fact it was not. Candidates for the primaries were selected by special committees. Not even all party members had the right to vote, but only about 200,000 specially selected electors. In addition, the results of voting on the primaries were in most cases ignored. Of the 80 lists of regional groups of candidates for the State Duma, nominated by the congress of Unitpared Russia, only 8 lists coincided with the lists of winners of the primaries. All the same, the event played a role in the elimination of candidates: there were cases when the current deputies of the State Duma, having seen that they did not enjoy the support of electors, withdrew their candidacies.

In the future, United Russia has sometimes resorted to an "open" model of primaries, which allows voting to all interested voters. In 2014, in the primaries of the "United Russia" before the elections to the Moscow City Duma, any Muscovite could vote, and not only registered electors.

In 2016, the primaries for the selection of candidates for parliamentary elections were held by four parties: United Russia, People's Freedom Party, the Party of Growth and the Green Alliance. The most massive were 22 May 2016 primaries of the United Russia, which could vote for every citizen who has an active electoral right. However, the primaries, as well as earlier, were not binding for the leadership of United Russia: a number of winners of the primaries were withdrawn by the leadership without any explanation of reasons, and in 18 single-seat constituencies the party did not nominate any candidates. A striking example was the Nizhny Tagil constituency, where the candidate from the United Russia was approved candidate, who took the 4th place in the primaries. Finally, a number of candidates were included in the party list on the proposal of the party leader Dmitry Medvedev from among those who did not even participate in the primaries.

In 2017, the Party of Growth holds the primaries for the nomination of candidates for the presidential election. These are the first presidential primaries in the history of Russia. However, voting for candidates will take place via the Internet within three months, and, according to the spokesman of the party, the results of the primaries will not be mandatory for the nomination of the candidate and the party convention may nominate another candidate who does not even participate in the primaries, or even not nominate candidates and support President Vladimir Putin, if he decides to be re-elected.

Poland

 * 2019 Civic Platform presidential primary
 * 2020 Confederation Liberty and Independence presidential primaries

Portugal

 * 2014 Portuguese Socialist Party prime ministerial primary

United Kingdom
For the 2010 general election, the Conservative Party used open primaries to select two candidates for Member of Parliament. Further open primaries were used to select some Conservative candidates for the 2015 general election, and there are hopes other parties may nominate future candidates in this way.

In Canada
As in Europe, nomination meetings and leadership elections (somewhat similar to primary elections) in Canada are not organized by the public administration but by parties themselves. Political parties participate in federal elections to the House of Commons, in legislative elections in all ten provinces, and in Yukon. (The legislatures and elections in the Northwest Territories and Nunavut are non-partisan.)

Local candidates
Typically, in the months before an anticipated general election, local riding associations of political parties in each electoral district will schedule and announce a Nomination Meeting (similar to a nominating caucus in the United States). Would-be candidates will then file nomination papers with the association, and usually will devote time to solicit existing party members, and to sign up new party members who will also support them at the nomination meeting. At the meeting, typically each candidate will speak, and then members in attendance will vote. The electoral system most often used is an exhaustive ballot system; if no candidate has over 50% of the votes, the candidate with the lowest number of votes will be dropped and another ballot will be held. Also, other candidates who recognize that they will probably not win may withdraw between ballots, and may "throw their support" to (encourage their own supporters to vote for) another candidate. After the nomination meeting, the candidate and the association will obtain approval from party headquarters, and file the candidate's official nomination papers and necessary fees and deposits with Elections Canada or the provincial/territorial election commissions as appropriate.

At times, party headquarters may overturn an association's chosen candidate; for example, if any scandalous information about the candidate comes to light after the nomination. A party headquarters may also "parachute" a prominent candidate into an easy-to-win riding, removing the need to have a nomination meeting. These situations only come up infrequently, as they tend to cause disillusionment among a party's supporters.

Party leaders
Canadian political parties also organize their own elections of party leaders. Not only will the party leader run for a seat in their own chosen riding, they will also become Prime Minister (in a federal election) or Premier (in a province or territory) should their party secure the confidence of parliament (usually by winning the most seats). Thus, a leadership election is also considered to be one for the party's de facto candidate for Prime Minister or Premier. If the party does not secure the confidence of parliament, but wins the next most amount of seats, the party leader will become Leader of the Official Opposition; if the party comes third or lower but maintains official party status, the leader will still be recognized as the leader of their party, and will be responsible for co-ordinating the activities and affairs of their party's caucus in the legislature.

In the past, Canadian political parties chose party leaders through an American-style delegated leadership convention. Local riding associations would choose delegates, usually in a manner similar to how they would choose a candidate for election. These delegates typically said explicitly which leadership candidate they would support. Those delegates, as well as other delegates (e.g. sitting party members of Parliament or the legislature, or delegates from party-affiliated organizations such as labor unions in the case of the New Democratic Party), would then vote, again using the exhaustive ballot method, until a leader was chosen. Some provincial political parties retain the delegated convention format.

Lately, Canada's major political parties have moved towards direct elections for federal leadership. A leadership convention is still scheduled, but all party members have a chance to vote for the new leader. Typically, members may vote either in person at the convention, online, or through a mail-in ballot.

Instant-runoff is used in whole or in part to elect the leaders of the three largest federal political parties in Canada: the Liberal Party of Canada, the Conservative Party of Canada, and the New Democratic Party, albeit the New Democratic Party uses a mixture of IRV and exhaustive voting, allowing each member to choose one format or the other for their vote (as was used in their 2017 leadership election). In 2013, members of the Liberal Party of Canada elected Justin Trudeau as party leader through IRV in a national leadership election. The Conservative Party used IRV (where each of the party's 338 riding associations are weighted equally, regardless of how many members voted in each riding) to elect Erin O'Toole as party leader in 2020, Andrew Scheer in 2017, and Stephen Harper in 2004.

Americas

 * Argentina
 * In Argentina, the presidential primary election is structured as a blanket primary system. Within this framework, voters have the freedom to select a single candidate for each available position, irrespective of party affiliations. This approach holds historical significance, as it was previously employed in the United States as well.
 * Chile
 * 2017 Chilean presidential primaries
 * Colombia:
 * In the 2006 presidential elections, the Liberal Party, and the socialist Alternative Democratic Pole held primary elections, electing Horacio Serpa as the Liberal candidate, and Carlos Gaviria as candidate of the Alternative Democratic Pole.
 * In the 2010 presidential elections, four parties held primary elections: The Liberal Party elected former minister Rafael Pardo as candidate, the Democratic Pole elected senator Gustavo Petro, the Conservative Party chose ambassador Noemi Sanin, and the Green Party chose former mayor of Bogota Antanas Mockus.
 * Costa Rica: the country's three main political parties, the National Liberation Party, the Social Christian Unity Party, and the Citizens' Action Party, have all run primary elections on several different occasions.
 * Uruguay
 * In Uruguay, a blanket primary election is held every five years to elect the national and department conventions of each party, which select their presidential and intendant candidates. All parties must participate, however voting is voluntary unlike the other instances in the electoral process.

Asia

 * Hong Kong
 * 2020 Hong Kong pro-democracy primaries
 * Republic of China (Taiwan):
 * 2019 Democratic Progressive Party presidential primary
 * 2019 Kuomintang presidential primary
 * South Korea
 * 2017 South Korean presidential election
 * United New Democratic Party presidential primaries
 * India
 * 2022 Indian National Congress leadership election
 * Prime ministerial candidacy of Narendra Modi

Oceania

 * Australia
 * The Australian Labor Party and the National Party have conducted limited experiments with primary-style preselections.
 * In 2018, the New South Wales branch of the Liberal Party rejected a motion by former Prime Minister Tony Abbott to have primary-style preselections.

title: Primary election