Enzyme-catalysed reactions

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

J. W. Cornforth (Sussex) stereochemistry of enzyme-catalysed reactions. 

Most enzymes catalyse reactions and follow Michaelis-Menten kinetics. The rate can be described on the basis of the concentration of the substrate and the enzymes. For a single enzyme and single substrate, the rate equation is ... 

In general, enzymes are proteins and cany charges the perfect assumption for enzyme reactions would be multiple active sites for binding substrates with a strong affinity to hold on to substrate. In an enzyme mechanism, the second substrate molecule can bind to the enzyme as well, which is based on the free sites available in the dimensional structure of the enzyme. Sometimes large amounts of substrate cause the enzyme-catalysed reaction to diminish such a phenomenon is known as inhibition. It is good to concentrate on reaction mechanisms and define how the enzyme reaction may proceed in the presence of two different substrates. The reaction mechanisms with rate constants are defined as ... 

Such a subunit structure permits the construction of the virus partieles by a proeess in which the subunits self-assemble into structures held together by non-eovalent intermolecular forces as occurs in the process of erystallization. This eliminates the need for a sequenee of enzyme-catalysed reactions for coat synthesis. It also provides an automatic quality-control system, as subunits which may have major stmctural defects fail to become ineorporated into complete partieles. 

The value for Qiq of chemical and enzyme-catalysed reactions lies between 2 and 3. The values of disinfectants vary widely thus, for phenol it is 4, for bntanol 28,... 

Oxidation is initiated by formation of radicals which may be the result of enzyme catalysed reactions like oxygen activation by xanthine oxidase in... 

Hydrogen motion, H+, H or H, is often involved in the rate-limiting step of many enzyme catalysed reactions. Here, QM tunnelling can be important and is reflected in the values of the measured kinetic isotope effects (KIEs) [75], Enzyme motion... 

The feature of xanthine oxidase which is no doubt of the greatest chemical interest, is the presence of several non-protein components. Much effort has been expended in attempting to elucidate the respective roles of iron, flavin and molybdenum in the various enzyme catalysed reactions. Numerous studies of the iron constituent have been made of late (45, 46, 47, 48, 49, 50), it having been found to be of the iron-sulphur (51 a, 51 b) type. Neither iron (19) nor molybdenum (31) can be removed reversibly from the enzyme, though the FAD can be (52, see below). 

Stereospecific enzymes catalyse reactions with one type of optical isomer but may also react with a series of related compounds of the same configuration. Many proteolytic enzymes hydrolyse only peptide bonds linking laevorotatory (L-) amino acids. 

Such enzymes catalyse reactions involving electron transfer. Oxidases use molecular oxygen as an electron acceptor (Scheme 10.10). Dehydrogenases remove hydrogen atoms from the substrate and transfer them to an acceptor other than oxygen. 

After more than 20 years, Walde et al. (1994) returned in a way to coacervate experiments, although using other methods. Walde (from the Luisi group) repeated nucleotide polymerisation of ADP to give polyadenylic acid, catalysed by polynucleotide phosphorylase (PNPase). But instead of Oparin s coacervates, the Zurich group used micelles and self-forming vesicles. They were able to demonstrate that enzyme-catalysed reactions can take place in these molecular structures, which can thus serve as protocell models. Two different supramolecular systems were used ... 

C.J. Gray, in Enzyme-catalysed Reactions. Van Nostrand Reinhold Co., London (1971). 

Acid and base catalysis of a chemical reaction involves the assistance by acid or base of a particular proton-transfer step in the reaction. Many enzyme catalysed reactions involve proton transfer from an oxygen or nitrogen centre at some stage in the mechanism, and often the role of the enzyme is to facilitate a proton transfer by acid or base catalysis. Proton transfer at one site in the substrate assists formation and/or rupture of chemical bonds at another site in the substrate. To understand these complex processes, it is necessary to understand the individual proton-transfer steps. The fundamental theory of simple proton transfers between oxygen and nitrogen acids and... 

Very few enzyme-catalysed reactions involving the reduction of alkenes have achieved any degree of recognition in synthetic organic chemistry. Indeed the only transformation of note involves the reduction of a, (3-unsaturated aldehydes and ketones. For example, bakers yeast reduction of (Z)-2-bromo-3-phenylprop-2-enal yields (S)-2-bromo-3-phenylpropanol in practically quantitative yield (99 % ee) when a resin is employed to control substrate concen-tration[50]. Similarly (Z)-3-bromo-4-phenylbut-3-en-2-one yields 2(5), 3(,S)-3-bromo-4-phenylbutan-2-ol (80% yield, >95% ee)[51]. Carbon-carbon double bond reductases can be isolated one such enzyme from bakers yeast catalyses the reduction of enones of the type Ar—CH = C(CH3)—COCH3 to the corresponding (S)-ketones in almost quantitative yields and very high enantiomeric excesses[52]. 

In addition there is at least one area where enzyme-catalysed reactions have established themselves as the first line of attack for solving synthetic problems that area involves the transformations of carbohydrates. Indeed, biocatalysed transformations of saccharides is becoming increasingly popular and roughly 10% of the recent literature (Year 2000) on biotransformations involves the preparation and modification of carbohydrates. Early literature on chemoenzy-matic approaches for the synthesis of saccharides and mimetics has been reviewed by a pioneer in the field, C.-H. Wong[158]. For one of the most popular areas, enzyme-catalysed glycosylation reactions, a useful survey is also available, penned by the same senior author[159]. 

The sharp rise in the number of enzymes capable of promoting coupling reactions involving carbohydrate moieties mirrors the increased activity and interest in this field. Obviously this will provide an important niche area where enzyme-catalysed reactions will probably remain the methodology of choice at least for the foreseeable future. 

The species Y is also probably non-existent in most of the enzyme catalysed reactions involving only one substrate. In acidic or basic reactions, Y and W do, however, play roles. In acid catalysed reactions, where C is an acid, transfer of proton to S takes place giving Y as a conjugate base of C. W is a basic or amphoteric substance which accepts a proton from X. In base catalysis, Y is a conjugate acid to the base C while W transfers a proton to X and may be the solvent or another acidic substance. With regard to the stability of the intermediate complex X, the two possibilities, which may be considered, are ... 

Certain constituents when added to the reaction mixture, slow down the rate of reaction. This phenomena is called inhibition and constituent called inhibitor. Such an effect is similar to the negative catalysis. But the constituent usually undergoes chemical change, inhibition is the preferred term. Inhibition may occur in chain reactions, enzyme catalysed reactions, surface reactions or many reversible or irreversible reactions. A trace amount of an inhibitor may cause a marked decrease in the rate of reaction. The inhibitor sometimes combines with a catalyst and prevents it from catalyzing the reaction. 

M. A. Savageau, Development of fractal kinetic theory for enzyme catalysed reactions and implications for the design of biochemical pathways. BioSystems 47(1 2), 9 36 (1998). 

The thermodynamic activation parameters for the enzyme-catalysed reaction are very different from those for the uncatalysed process (Albers et at., 1990). For the isomerization of succinyl-alanyl-leucyl-prolylphenylalanyl-p-nitroanilide catalysed by recombinant human FK binding protein AH = 5.85 kcal mol"1 and AS = -44. e.u. This compares with figures of 18.9 kcal mol 1 and — l.lbe.u. for the uncatalysed reaction of the same substrate. Probably a different step is rate determining in the enzyme-catalysed reaction. 

Y, then C-OR bond breaking should be even more dependent on, and thus sensitive to, the orientation of the lone pairs on the single donor oxygen of [91], This conclusion is relevant to the reactions of glycosides, and has important implications for the enzyme-catalysed reactions at their anomeric centres. 

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