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79-506: 1V04 5444 18979 ENSG00000005421 ENSMUSG00000002588 P27169 P52430 NM_000446 NM_011134 NP_000437 NP_035264 Paraoxonase 1 ( PON1 ) also known as Serum paraoxonase and arylesterase 1 , A esterase , homocysteine thiolactonase or serum aryldialkylphosphatase 1 , is an enzyme that in humans is encoded by the PON1 gene . Paraoxonase 1 has esterase and more specifically paraoxonase activity. PON1

158-487: A catalytic triad , stabilize charge build-up on the transition states using an oxyanion hole , complete hydrolysis using an oriented water substrate. Enzymes are not rigid, static structures; instead they have complex internal dynamic motions – that is, movements of parts of the enzyme's structure such as individual amino acid residues, groups of residues forming a protein loop or unit of secondary structure , or even an entire protein domain . These motions give rise to

237-489: A conformational ensemble of slightly different structures that interconvert with one another at equilibrium . Different states within this ensemble may be associated with different aspects of an enzyme's function. For example, different conformations of the enzyme dihydrofolate reductase are associated with the substrate binding, catalysis, cofactor release, and product release steps of the catalytic cycle, consistent with catalytic resonance theory . Substrate presentation

316-511: A type of enzyme rather than being like an enzyme, but even in the decades since ribozymes' discovery in 1980–1982, the word enzyme alone often means the protein type specifically (as is used in this article). An enzyme's specificity comes from its unique three-dimensional structure . Like all catalysts, enzymes increase the reaction rate by lowering its activation energy . Some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example

395-428: A P−C bond, these compounds are in the technical sense not organophosphorus compounds but esters of phosphoric acid. Many derivatives are found in nature, such as phosphatidylcholine . Phosphate ester are synthesized by alcoholysis of phosphorus oxychloride. A variety of mixed amido-alkoxo derivatives are known, one medically significant example being the anti-cancer drug cyclophosphamide . Also derivatives containing

474-429: A catalytic alkylant to the former: In the environment, all these phosphorus(V) compounds break down via hydrolysis to eventually afford phosphate and the organic alcohol or amine from which they are derived. Phosphonates are esters of phosphonic acid and have the general formula RP(=O)(OR') 2 . Phosphonates have many technical applications, a well-known member being glyphosate , better known as Roundup. With

553-474: A first step and then checks that the product is correct in a second step. This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases. Similar proofreading mechanisms are also found in RNA polymerase , aminoacyl tRNA synthetases and ribosomes . Conversely, some enzymes display enzyme promiscuity , having broad specificity and acting on

632-464: A quantitative theory of enzyme kinetics, which is referred to as Michaelis–Menten kinetics . The major contribution of Michaelis and Menten was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis–Menten complex in their honor. The enzyme then catalyzes the chemical step in

711-439: A range of different physiologically relevant substrates. Many enzymes possess small side activities which arose fortuitously (i.e. neutrally ), which may be the starting point for the evolutionary selection of a new function. To explain the observed specificity of enzymes, in 1894 Emil Fischer proposed that both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. This

790-430: A reverse Arbuzov rearrangement to a dialkylthiophosphinate ester. Compounds with the formula [PR 4 ]X comprise the phosphonium salts . These species are tetrahedral phosphorus(V) compounds. From the commercial perspective, the most important member is tetrakis(hydroxymethyl)phosphonium chloride , [P(CH 2 OH) 4 ]Cl, which is used as a fire retardant in textiles . Approximately 2M kg are produced annually of

869-451: A species' normal level; as a result, enzymes from bacteria living in volcanic environments such as hot springs are prized by industrial users for their ability to function at high temperatures, allowing enzyme-catalysed reactions to be operated at a very high rate. Enzymes are usually much larger than their substrates. Sizes range from just 62 amino acid residues, for the monomer of 4-oxalocrotonate tautomerase , to over 2,500 residues in

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948-446: A steady level inside the cell. For example, NADPH is regenerated through the pentose phosphate pathway and S -adenosylmethionine by methionine adenosyltransferase . This continuous regeneration means that small amounts of coenzymes can be used very intensively. For example, the human body turns over its own weight in ATP each day. As with all catalysts, enzymes do not alter the position of

1027-442: A thermodynamically unfavourable one so that the combined energy of the products is lower than the substrates. For example, the hydrolysis of ATP is often used to drive other chemical reactions. Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products. The rate data used in kinetic analyses are commonly obtained from enzyme assays . In 1913 Leonor Michaelis and Maud Leonora Menten proposed

1106-457: Is k cat , also called the turnover number , which is the number of substrate molecules handled by one active site per second. The efficiency of an enzyme can be expressed in terms of k cat / K m . This is also called the specificity constant and incorporates the rate constants for all steps in the reaction up to and including the first irreversible step. Because the specificity constant reflects both affinity and catalytic ability, it

1185-838: Is orotidine 5'-phosphate decarboxylase , which allows a reaction that would otherwise take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the equilibrium of a reaction. Enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules: inhibitors are molecules that decrease enzyme activity, and activators are molecules that increase activity. Many therapeutic drugs and poisons are enzyme inhibitors. An enzyme's activity decreases markedly outside its optimal temperature and pH , and many enzymes are (permanently) denatured when exposed to excessive heat, losing their structure and catalytic properties. Some enzymes are used commercially, for example, in

1264-428: Is a method for the preparation of aminophosphonates. These compounds contain a very inert bond between phosphorus and carbon. Consequently, they hydrolyze to give phosphonic and phosphinic acid derivatives, but not phosphate. Phosphine oxides (designation σ λ ) have the general structure R 3 P=O with formal oxidation state V. Phosphine oxides form hydrogen bonds and some are therefore soluble in water. The P=O bond

1343-421: Is a process where the enzyme is sequestered away from its substrate. Enzymes can be sequestered to the plasma membrane away from a substrate in the nucleus or cytosol. Or within the membrane, an enzyme can be sequestered into lipid rafts away from its substrate in the disordered region. When the enzyme is released it mixes with its substrate. Alternatively, the enzyme can be sequestered near its substrate to activate

1422-454: Is called enzymology and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules , also called ribozymes . They are sometimes described as

1501-437: Is described by "EC" followed by a sequence of four numbers which represent the hierarchy of enzymatic activity (from very general to very specific). That is, the first number broadly classifies the enzyme based on its mechanism while the other digits add more and more specificity. The top-level classification is: These sections are subdivided by other features such as the substrate, products, and chemical mechanism . An enzyme

1580-535: Is encoded by the PON1 gene, which is located on the long arm of chromosome 7. PON1 activity can vary by over 40 fold between individuals. The biggest effect on PON1 activity levels is through PON1 genetic polymorphisms. Many nutritional, life-style and pharmaceutical modulators of PON1 are also known. The coding region PON1-Q192R polymorphism determines a substrate dependent effect on activity. Many organophosphates used in pesticides, such as paraoxon , are hydrolysed faster by

1659-749: Is fully specified by four numerical designations. For example, hexokinase (EC 2.7.1.1) is a transferase (EC 2) that adds a phosphate group (EC 2.7) to a hexose sugar, a molecule containing an alcohol group (EC 2.7.1). Sequence similarity . EC categories do not reflect sequence similarity. For instance, two ligases of the same EC number that catalyze exactly the same reaction can have completely different sequences. Independent of their function, enzymes, like any other proteins, have been classified by their sequence similarity into numerous families. These families have been documented in dozens of different protein and protein family databases such as Pfam . Non-homologous isofunctional enzymes . Unrelated enzymes that have

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1738-441: Is known, being derived from P(C 6 H 5 ) 4 by reaction with phenyllithium . Phosphorus ylides are unsaturated phosphoranes, known as Wittig reagents , e.g. CH 2 P(C 6 H 5 ) 3 . These compounds feature tetrahedral phosphorus(V) and are considered relatives of phosphine oxides. They also are derived from phosphonium salts, but by deprotonation not alkylation. Phosphites, sometimes called phosphite esters , have

1817-473: Is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase . Examples are lactase , alcohol dehydrogenase and DNA polymerase . Different enzymes that catalyze the same chemical reaction are called isozymes . The International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the EC numbers (for "Enzyme Commission") . Each enzyme

1896-418: Is often referred to as "the lock and key" model. This early model explains enzyme specificity, but fails to explain the stabilization of the transition state that enzymes achieve. In 1958, Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continuously reshaped by interactions with the substrate as the substrate interacts with

1975-462: Is only one of several important kinetic parameters. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis–Menten constant ( K m ), which is the substrate concentration required for an enzyme to reach one-half its maximum reaction rate; generally, each enzyme has a characteristic K M for a given substrate. Another useful constant

2054-404: Is seen. This is shown in the saturation curve on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES complex. At the maximum reaction rate ( V max ) of the enzyme, all the enzyme active sites are bound to substrate, and the amount of ES complex is the same as the total amount of enzyme. V max

2133-403: Is the ribosome which is a complex of protein and catalytic RNA components. Enzymes must bind their substrates before they can catalyse any chemical reaction. Enzymes are usually very specific as to what substrates they bind and then the chemical reaction catalysed. Specificity is achieved by binding pockets with complementary shape, charge and hydrophilic / hydrophobic characteristics to

2212-491: Is the first discovered member of a multigene family also containing PON2 and PON3 , the genes for which are located adjacent to each other on chromosome 7. PON1 on HDL (different from soluble PON1) is responsible for significant atheroprotection rendered by the HDL. Human PON1 is a glycoprotein composed of 354 amino acids and has a molecular weight of 43,000 daltons which associates with high-density lipoprotein (HDL, cholesterol) in

2291-790: Is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 10 to 10 (M s ). At this point every collision of the enzyme with its substrate will result in catalysis, and the rate of product formation is not limited by the reaction rate but by the diffusion rate. Enzymes with this property are called catalytically perfect or kinetically perfect . Example of such enzymes are triose-phosphate isomerase , carbonic anhydrase , acetylcholinesterase , catalase , fumarase , β-lactamase , and superoxide dismutase . The turnover of such enzymes can reach several million reactions per second. But most enzymes are far from perfect:

2370-514: Is variable, which can lead to confusion. In industrial and environmental chemistry, an organophosphorus compound need contain only an organic substituent , but need not have a direct phosphorus-carbon (P-C) bond. Thus a large proportion of pesticides (e.g., malathion ), are often included in this class of compounds. Phosphorus can adopt a variety of oxidation states , and it is general to classify organophosphorus compounds based on their being derivatives of phosphorus(V) vs phosphorus(III), which are

2449-469: Is very polar with a dipole moment of 4.51 D for triphenylphosphine oxide . Compounds related to phosphine oxides include phosphine imides (R 3 PNR') and related chalcogenides (R 3 PE, where E = S , Se , Te ). These compounds are some of the most thermally stable organophosphorus compounds. In general, they are less basic than the corresponding phosphine oxides, which can adduce to thiophosphoryl halides: Some phosphorus sulfides can undergo

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2528-611: The DNA polymerases ; here the holoenzyme is the complete complex containing all the subunits needed for activity. Coenzymes are small organic molecules that can be loosely or tightly bound to an enzyme. Coenzymes transport chemical groups from one enzyme to another. Examples include NADH , NADPH and adenosine triphosphate (ATP). Some coenzymes, such as flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), thiamine pyrophosphate (TPP), and tetrahydrofolate (THF), are derived from vitamins . These coenzymes cannot be synthesized by

2607-562: The Wittig reaction and as supporting phosphine ligands in homogeneous catalysis . Their nucleophilicity is evidenced by their reactions with alkyl halides to give phosphonium salts . Phosphines are nucleophilic catalysts in organic synthesis , e.g. the Rauhut–Currier reaction and Baylis-Hillman reaction . Phosphines are reducing agents , as illustrated in the Staudinger reduction for

2686-511: The law of mass action , which is derived from the assumptions of free diffusion and thermodynamically driven random collision. Many biochemical or cellular processes deviate significantly from these conditions, because of macromolecular crowding and constrained molecular movement. More recent, complex extensions of the model attempt to correct for these effects. Enzyme reaction rates can be decreased by various types of enzyme inhibitors. A competitive inhibitor and substrate cannot bind to

2765-584: The 55M allele. The -108C allele has greater promoter activity than the -108T allele which results in different serum activities. The distribution of the PON1 polymorphisms varies with ethnicity. The frequency of the PON1-192R allele increases the further from Europe a population originates, the frequency in Caucasians of 15-30% increases to 70-90% in Far Eastern Oriental and Sub-Saharan African populations. In

2844-879: The PON1 gene significantly affect the catalytic ability of the enzyme. PON1 ( paraoxonase 1) is also a major anti- atherosclerotic component of high-density lipoprotein (HDL). The PON1 gene is activated by PPAR-γ , which increases synthesis and release of paraoxonase 1 enzyme from the liver, reducing atherosclerosis . PON1 is a highly promiscuous enzyme capable of hydrolysing a wide variety of substrates, such as lactones , including thiolactones and pharmaceutical agents such as statins. PON1 substrates also include glucuronide drugs, arylesters, cyclic carbonates, organophosphorus pesticides and nerve gases such as sarin, soman and VX, oestrogen esters and lipid peroxides ( oxidized lipids). Oxidized polyunsaturated fatty acids (notably in oxidized low-density lipoprotein ) form lactone-like structures that are PON substrates. PON1 in humans

2923-514: The PON1-R allozyme . Other substrates such as diazoxon, lipid-peroxides and sarin are hydrolysed more rapidly by the PON1-Q allozyme. Both the coding region PON1-L55M and the promoter region PON1-T-108C polymorphisms are associated with different serum concentrations and therefore activities. The 55L allele results in significantly higher PON1 mRNA and serum protein levels and therefore activity compared to

3002-437: The active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in redox reactions. Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins . An enzyme together with the cofactor(s) required for activity is called a holoenzyme (or haloenzyme). The term holoenzyme can also be applied to enzymes that contain multiple protein subunits, such as

3081-502: The active site. Organic cofactors can be either coenzymes , which are released from the enzyme's active site during the reaction, or prosthetic groups , which are tightly bound to an enzyme. Organic prosthetic groups can be covalently bound (e.g., biotin in enzymes such as pyruvate carboxylase ). An example of an enzyme that contains a cofactor is carbonic anhydrase , which uses a zinc cofactor bound as part of its active site. These tightly bound ions or molecules are usually found in

3160-465: The acute and chronic harmful effects of these compounds. Low PON1 activity found in children may increase their susceptibility to organophosphates. Because PON1-Q is more protective against sarin than PON1-R, the PON1-R allele and low PON1-Q activity levels are associated with Gulf War Illness . The greatest research interest has been the role of PON1 in atherosclerosis, where, because of its ability to remove harmful oxidised-lipids, PON1 protects against

3239-407: The animal fatty acid synthase . Only a small portion of their structure (around 2–4 amino acids) is directly involved in catalysis: the catalytic site. This catalytic site is located next to one or more binding sites where residues orient the substrates. The catalytic site and binding site together compose the enzyme's active site . The remaining majority of the enzyme structure serves to maintain

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3318-578: The average values of k c a t / K m {\displaystyle k_{\rm {cat}}/K_{\rm {m}}} and k c a t {\displaystyle k_{\rm {cat}}} are about 10 5 s − 1 M − 1 {\displaystyle 10^{5}{\rm {s}}^{-1}{\rm {M}}^{-1}} and 10 s − 1 {\displaystyle 10{\rm {s}}^{-1}} , respectively. Michaelis–Menten kinetics relies on

3397-502: The body de novo and closely related compounds (vitamins) must be acquired from the diet. The chemical groups carried include: Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 1000 enzymes are known to use the coenzyme NADH. Coenzymes are usually continuously regenerated and their concentrations maintained at

3476-471: The chemical equilibrium of the reaction. In the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly. For example, carbonic anhydrase catalyzes its reaction in either direction depending on the concentration of its reactants: The rate of a reaction is dependent on the activation energy needed to form the transition state which then decays into products. Enzymes increase reaction rates by lowering

3555-636: The chloride and the related sulfate. They are generated by the reaction of phosphine with formaldehyde in the presence of the mineral acid: A variety of phosphonium salts can be prepared by alkylation and arylation of organophosphines: The methylation of triphenylphosphine is the first step in the preparation of the Wittig reagent. The parent phosphorane (σ λ ) is PH 5 , which is unknown. Related compounds containing both halide and organic substituents on phosphorus are fairly common. Those with five organic substituents are rare, although P(C 6 H 5 ) 5

3634-454: The circulation. Serum PON1 is secreted mainly by the liver, although local synthesis occurs in several tissues and PON1 protein is found in almost all tissues. X-ray crystallography has revealed the structure of PON1 to be a 6 bladed propeller with a unique lid structure covering the active site passage which allows association with HDL. PON1 is responsible for hydrolysing organophosphate pesticides and nerve gasses . Polymorphisms in

3713-495: The commercial perspective, the most important phosphine is triphenylphosphine , several million kilograms being produced annually. It is prepared from the reaction of chlorobenzene , PCl 3 , and sodium. Phosphines of a more specialized nature are usually prepared by other routes. Phosphorus halides undergo nucleophilic displacement by organometallic reagents such as Grignard reagents . Organophosphines are nucleophiles and ligands . Two major applications are as reagents in

3792-426: The compound phosphorine , one carbon atom in benzene is replaced by phosphorus. Species of this type are relatively rare but for that reason are of interest to researchers. A general method for the synthesis of phosphaalkenes is by 1,2-elimination of suitable precursors, initiated thermally or by base such as DBU , DABCO , or triethylamine : Thermolysis of Me 2 PH generates CH 2 =PMe, an unstable species in

3871-421: The condensed phase. Compounds where phosphorus exists in a formal oxidation state of less than III are uncommon, but examples are known for each class. Organophosphorus(0) species are debatably illustrated by the carbene adducts, [P(NHC)] 2 , where NHC is an N-heterocyclic carbene . With the formulae (RP) n and (R 2 P) 2 , respectively, compounds of phosphorus(I) and (II) are generated by reduction of

3950-425: The conversion of starch to sugars by plant extracts and saliva were known but the mechanisms by which these occurred had not been identified. French chemist Anselme Payen was the first to discover an enzyme, diastase , in 1833. A few decades later, when studying the fermentation of sugar to alcohol by yeast , Louis Pasteur concluded that this fermentation was caused by a vital force contained within

4029-609: The conversion of organic azides to amines and in the Mitsunobu reaction for converting alcohols into esters. In these processes, the phosphine is oxidized to phosphorus(V). Phosphines have also been found to reduce activated carbonyl groups, for instance the reduction of an α-keto ester to an α-hydroxy ester. Compounds with carbon phosphorus(III) multiple bonds are called phosphaalkenes (R 2 C=PR) and phosphaalkynes (RC≡P). They are similar in structure, but not in reactivity, to imines (R 2 C=NR) and nitriles (RC≡N), respectively. In

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4108-641: The corresponding phosphonous and phosphinous chlorides ((PCl 2 R') and (PClR' 2 ) , respectively). The latter are produced by reaction of a phosphorus trichloride with a poor metal -alkyl complex, e.g. organomercury , organolead , or a mixed lithium - organoaluminum compound. The parent compound of the phosphines is PH 3 , called phosphine in the US and British Commonwealth, but phosphane elsewhere. Replacement of one or more hydrogen centers by an organic substituents (alkyl, aryl), gives PH 3−x R x , an organophosphine, generally referred to as phosphines. From

4187-636: The development of atherosclerosis. PON1 also protects against bacterial infection by destroying the bacterial signalling molecules that cause gram negative bacteria to invade human tissue and form colonies, thus PON1 contributes to the bodies innate immunity. Recently it has been suggested that PON1 has a role in healthy aging, however, the mechanism is currently unknown. PON1 activity is low in infants compared to adults. A study of Mexican-American children showed that PON1 activity increased 3.5 times between birth and age seven. An association between PON1 gene polymorphism and susceptibility to Parkinson's disease

4266-433: The energy of the transition state. First, binding forms a low energy enzyme-substrate complex (ES). Second, the enzyme stabilises the transition state such that it requires less energy to achieve compared to the uncatalyzed reaction (ES ). Finally the enzyme-product complex (EP) dissociates to release the products. Enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive"

4345-587: The enzyme urease was a pure protein and crystallized it; he did likewise for the enzyme catalase in 1937. The conclusion that pure proteins can be enzymes was definitively demonstrated by John Howard Northrop and Wendell Meredith Stanley , who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin . These three scientists were awarded the 1946 Nobel Prize in Chemistry. The discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography . This

4424-483: The enzyme at the same time. Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, the drug methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase , which catalyzes the reduction of dihydrofolate to tetrahydrofolate. The similarity between the structures of dihydrofolate and this drug are shown in the accompanying figure. This type of inhibition can be overcome with high substrate concentration. In some cases,

4503-403: The enzyme. As a result, the substrate does not simply bind to a rigid active site; the amino acid side-chains that make up the active site are molded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases , the substrate molecule also changes shape slightly as it enters the active site. The active site continues to change until

4582-427: The enzyme. For example, the enzyme can be soluble and upon activation bind to a lipid in the plasma membrane and then act upon molecules in the plasma membrane. Allosteric sites are pockets on the enzyme, distinct from the active site, that bind to molecules in the cellular environment. These molecules then cause a change in the conformation or dynamics of the enzyme that is transduced to the active site and thus affects

4661-465: The formula (HO) 2 P(O)CH 2 NHCH 2 CO 2 H, this derivative of glycine is one of the most widely used herbicides. Bisphosphonates are a class of drugs to treat osteoporosis . The nerve gas agent sarin , containing both C–P and F–P bonds, is a phosphonate. Phosphinates feature two P–C bonds, with the general formula R 2 P(=O)(OR'). A commercially significant member is the herbicide glufosinate . Similar to glyphosate mentioned above, it has

4740-613: The general structure P(OR) 3 with oxidation state +3. Such species arise from the alcoholysis of phosphorus trichloride: The reaction is general, thus a vast number of such species are known. Phosphites are employed in the Perkow reaction and the Michaelis–Arbuzov reaction . They also serve as ligands in organometallic chemistry. Intermediate between phosphites and phosphines are phosphonites (P(OR) 2 R') and phosphinite (P(OR)R' 2 ). Such species arise via alcoholysis reactions of

4819-401: The inhibitor can bind to a site other than the binding-site of the usual substrate and exert an allosteric effect to change the shape of the usual binding-site. Organophosphorus compound Phosphorus, like nitrogen , is in group 15 of the periodic table, and thus phosphorus compounds and nitrogen compounds have many similar properties. The definition of organophosphorus compounds

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4898-468: The mixture. He named the enzyme that brought about the fermentation of sucrose " zymase ". In 1907, he received the Nobel Prize in Chemistry for "his discovery of cell-free fermentation". Following Buchner's example, enzymes are usually named according to the reaction they carry out: the suffix -ase is combined with the name of the substrate (e.g., lactase is the enzyme that cleaves lactose ) or to

4977-528: The precise orientation and dynamics of the active site. In some enzymes, no amino acids are directly involved in catalysis; instead, the enzyme contains sites to bind and orient catalytic cofactors . Enzyme structures may also contain allosteric sites where the binding of a small molecule causes a conformational change that increases or decreases activity. A small number of RNA -based biological catalysts called ribozymes exist, which again can act alone or in complex with proteins. The most common of these

5056-421: The predominant classes of compounds. In a descriptive but only intermittently used nomenclature, phosphorus compounds are identified by their coordination number σ and their valency λ . In this system, a phosphine is a σ λ compound. Phosphate esters have the general structure P(=O)(OR) 3 feature P(V). Such species are of technological importance as flame retardant agents, and plasticizers . Lacking

5135-406: The reaction and releases the product. This work was further developed by G. E. Briggs and J. B. S. Haldane , who derived kinetic equations that are still widely used today. Enzyme rates depend on solution conditions and substrate concentration . To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation

5214-733: The reaction rate of the enzyme. In this way, allosteric interactions can either inhibit or activate enzymes. Allosteric interactions with metabolites upstream or downstream in an enzyme's metabolic pathway cause feedback regulation, altering the activity of the enzyme according to the flux through the rest of the pathway. Some enzymes do not need additional components to show full activity. Others require non-protein molecules called cofactors to be bound for activity. Cofactors can be either inorganic (e.g., metal ions and iron–sulfur clusters ) or organic compounds (e.g., flavin and heme ). These cofactors serve many purposes; for instance, metal ions can help in stabilizing nucleophilic species within

5293-410: The same enzymatic activity have been called non-homologous isofunctional enzymes . Horizontal gene transfer may spread these genes to unrelated species, especially bacteria where they can replace endogenous genes of the same function, leading to hon-homologous gene displacement. Enzymes are generally globular proteins , acting alone or in larger complexes . The sequence of the amino acids specifies

5372-717: The southern US, African-Americans are five times more likely to be RR than Caucasians. In contrast, the PON1-55M allele is much less frequent in Oriental and black African populations compared to Caucasians and are extremely rare or absent in some populations e.g. Thais. These ethnic differences in SNP distribution can lead to large activity differences between populations. PON1 was first discovered through its ability to hydrolyse and therefore detoxify organophosphorus compounds which are widely used as pesticides and nerve gases. PON1 protects humans from

5451-607: The structure CH 3 P(O)(OH)CH 2 CH 2 CH(NH 2 )CO 2 H. The Michaelis–Arbuzov reaction is the main method for the synthesis of these compounds. For example, dimethylmethylphosphonate (see figure above) arises from the rearrangement of trimethylphosphite , which is catalyzed by methyl iodide . In the Horner–Wadsworth–Emmons reaction and the Seyferth–Gilbert homologation , phosphonates are used in reactions with carbonyl compounds. The Kabachnik–Fields reaction

5530-412: The structure which in turn determines the catalytic activity of the enzyme. Although structure determines function, a novel enzymatic activity cannot yet be predicted from structure alone. Enzyme structures unfold ( denature ) when heated or exposed to chemical denaturants and this disruption to the structure typically causes a loss of activity. Enzyme denaturation is normally linked to temperatures above

5609-519: The substrate is completely bound, at which point the final shape and charge distribution is determined. Induced fit may enhance the fidelity of molecular recognition in the presence of competition and noise via the conformational proofreading mechanism. Enzymes can accelerate reactions in several ways, all of which lower the activation energy (ΔG , Gibbs free energy ) Enzymes may use several of these mechanisms simultaneously. For example, proteases such as trypsin perform covalent catalysis using

5688-405: The substrates. Enzymes can therefore distinguish between very similar substrate molecules to be chemoselective , regioselective and stereospecific . Some of the enzymes showing the highest specificity and accuracy are involved in the copying and expression of the genome . Some of these enzymes have " proof-reading " mechanisms. Here, an enzyme such as DNA polymerase catalyzes a reaction in

5767-399: The synthesis of antibiotics . Some household products use enzymes to speed up chemical reactions: enzymes in biological washing powders break down protein, starch or fat stains on clothes, and enzymes in meat tenderizer break down proteins into smaller molecules, making the meat easier to chew. By the late 17th and early 18th centuries, the digestion of meat by stomach secretions and

5846-443: The thiophosphoryl group (P=S) include the pesticide malathion . The organophosphates prepared on the largest scale are the zinc dithiophosphates , as additives for motor oil. Several million kilograms of this coordination complex are produced annually by the reaction of phosphorus pentasulfide with alcohols. Phosphoryl thioates are thermodynamically much stabler than thiophosphates, which can rearrange at high temperature or with

5925-438: The type of reaction (e.g., DNA polymerase forms DNA polymers). The biochemical identity of enzymes was still unknown in the early 1900s. Many scientists observed that enzymatic activity was associated with proteins, but others (such as Nobel laureate Richard Willstätter ) argued that proteins were merely carriers for the true enzymes and that proteins per se were incapable of catalysis. In 1926, James B. Sumner showed that

6004-486: The yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells." In 1877, German physiologist Wilhelm Kühne (1837–1900) first used the term enzyme , which comes from Ancient Greek ἔνζυμον (énzymon)  ' leavened , in yeast', to describe this process. The word enzyme

6083-581: Was first done for lysozyme , an enzyme found in tears, saliva and egg whites that digests the coating of some bacteria; the structure was solved by a group led by David Chilton Phillips and published in 1965. This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail. Enzymes can be classified by two main criteria: either amino acid sequence similarity (and thus evolutionary relationship) or enzymatic activity. Enzyme activity . An enzyme's name

6162-566: Was not found in a Chinese population. Enzyme Enzymes ( / ˈ ɛ n z aɪ m z / ) are proteins that act as biological catalysts by accelerating chemical reactions . The molecules upon which enzymes may act are called substrates , and the enzyme converts the substrates into different molecules known as products . Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes

6241-451: Was used later to refer to nonliving substances such as pepsin , and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897. In a series of experiments at the University of Berlin , he found that sugar was fermented by yeast extracts even when there were no living yeast cells in

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