Isomerization enzyme-catalyzed

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

Step 2 Enzyme catalyzed proton transfer steps cause migration of the double bond converting the mine formed m step 1 to an isomeric mine... 

Increasingly, biochemical transformations are used to modify renewable resources into useful materials (see Microbial transformations). Fermentation (qv) to ethanol is the oldest of such conversions. Another example is the ceU-free enzyme catalyzed isomerization of glucose to fmctose for use as sweeteners (qv). The enzymatic hydrolysis of cellulose is a biochemical competitor for the acid catalyzed reaction. 

Ionic dissociation of carbon-carbon a-bonds in hydrocarbons and the formation of authentic hydrocarbon salts, 30, 173 Ionization potentials, 4, 31 Ion-pairing effects in carbanion reactions, 15, 153 Ions, organic, charge density-NMR chemical shift correlations, 11, 125 Isomerization, permutational, of pentavalent phosphorus compounds, 9, 25 Isotope effects and quantum tunneling in enzyme-catalyzed hydrogen transfer. 

Enzyme-catalyzed reactions can be described at least at two distinct levels. At the basic level, the interconversion of substrates by enzymes is governed by a set of elementary steps, including enzyme substrate binding, isomerization and dissociation steps, see Fig. 6 for a schematic depiction. Assuming the intracellular medium is an ideal solution, each elementary step is governed by mass-action kinetics, that is, the reaction rates are proportional to the probability of collision of the reactants. For a reaction of the type... 

The observation of hidden reactions during solvolysis, through the use of chiral or isotopically labeled substrates has created considerable excitement in communities interested in the mechanisms of nonenzymatic and enzyme catalyzed reactions. These hidden reactions reveal something interesting about reaction mechanisms. However, chemists and biochemists are still working on the problem of extracting simple and definitive conclusions from analysis of data for these isomerization reactions. 

There have been a number of isolated studies of metal-ion catalyzed nucleophilic reactions of other groupings. Particularly interesting is the induced nucleophilic attack on olefins. Hydration is normally very sluggish. Enzymes can speed up such reactions. Aconitase, an iron-containing enzyme, catalyzes the isomerization of citric acid to isocitric acid, through the intermediacy of cis-aconitic acid. A possible mechanism has been suggested based on the following Co(III) model chemistry. Rapid cyclization of the maleate ester produces Ai and AS chelated malate half ester ... 

There are many examples of first-order reactions dissociation from a complex, decompositions, isomerizations, etc. The decomposition of gaseous nitrogen pentoxide (2N2O5 4NO2 + O2) was determined to be first order ( d[N205]/dt = k[N205j) as is the release of product from an enzyme-product complex (EP E -t P). In a single-substrate, enzyme-catalyzed reaction in which the substrate concentration is much less than the Michaelis constant (i.e., [S] K ) the reaction is said to be first-order since the Michaelis-Menten equation reduces to... 

Creighton and Murthy recently reviewed the stereochemistry and related mechanistic issues associated with enzyme-catalyzed isomerizations that proceed by 1,2-hydrogen transfer or by 1,3-aUytic hydrogen transfer. In the first case, the prototypical aldose-ketose isomerase is triose-phosphate isomerase (or TPl), an enzyme that uses the carboxylate of Glu-165 as a base for abstracting a proton from the substrate during catalysis. A -3-Keto-... 

High-pressure FT-IR spectroscopy has been used to clarify (1) the rotational isomerism of molecules, (2) characteristics of water and the water-head group, and (3) RSO3 Na4- interactions in reverse micellar aggregates in supercritical ethane. This work demonstrates interesting pressure, temperature, and salt effects on an enzyme-catalyzed esterification and/or maintenance of a one-phase microemulsion in supercritical fluids from practical and theoretical points of view (Ikushima, 1997). 

A closely related E. coli protein is a 79-kDa multifunctional enzyme that catalyzes four different reactions of fatty acid oxidation (Chapter 17). The amino-terminal region contains the enoyl hydratase activity.32 A quite different enzyme catalyzes dehydration of thioesters of (3-hydroxyacids such as 3-hydroxydecanoyl-acyl carrier protein (see Eq. 21-2) to both form and isomerize enoyl-ACP derivatives during synthesis of unsaturated fatty acids by E. coli. Again, a glutamate side chain is the catalytic base but an imidazole group of histidine has also been implicated.33 This enzyme is inhibited irreversibly by the N-acetylcysteamine thioester of 3-decynoic acids (Eq. 13-8). This was one of the first enzyme-activated inhibitors to be studied.34... 

In 1895, Emil Ficher proposed an enediol intermediate for this isomerization. As would be expected, the enzyme-catalyzed isomerization of glucose-6-phosphate in 2H20 is accompanied by incorporation of deuterium into the product fructose 6-phosphate at C-l. In the reverse reaction 2H-containing fructose 6-phosphate was found to react at only 45% of the rate of the 1H-containing compound. Thus, the primary deuterium isotope effect expected for a rate-limiting cleavage of the C-H bond was observed (see Chapter 12, Section B,3). 

At present most evidence favors, for the isomerization reactions, an enzyme-catalyzed rearrangement of the substrate radical produced initially during formation of the 5 -deoxyadenosine (Eq. 16-38).40CM01c... 

Cis-trans isomerization is an important step in the chemistry of vision, for example, the light-initiated, enzyme-catalyzed isomerization of cis to frans-retinal. 

First, the other hydroxyl group of mevalonate accepts a phosphate from ATP. The resulting compound rearranges in an enzyme-catalyzed reaction, eliminating both CO2 and phosphate. The 5-carbon compound that results, IPP, is rapidly isomerized with DMAPP. 

The alanine racemization catalyzed by alanine racemase is considered to be initiated by the transaldimination (Fig. 8.5).26) In this step, PLP bound to the active-site lysine residue forms the external Schiff base with a substrate alanine (Fig. 8.5, 1). The following a-proton abstraction produces the resonance-stabilized carbanion intermediates (Fig. 8.5, 2). If the reprotonation occurs on the opposite face of the substrate-PLP complex on which the proton-abstraction proceeds, the antipodal aldimine is formed (Fig. 8.5,3). The subsequent hydrolysis of the aldimine complex gives the isomerized alanine and PLP-form racemase. The random return of hydrogen to the carbanion intermediate is the distinguishing feature that differentiates racemization from reactions catalyzed by other pyridoxal enzymes such as transaminases. Transaminases catalyze the transfer of amino group between amino acid and keto acid, and the reaction is initiated by the transaldimination, followed by the a-proton abstraction from the substrate-PLP aldimine to form a resonance-stabilized carbanion. This step is common to racemases and transaminases. However, in the transamination the abstracted proton is then tranferred to C4 carbon of PLP in a highly stereospecific manner The re-protonation occurs on the same face of the PLP-substrate aldimine on which the a-proton is abstracted. With only a few exceptions,27,28) each step of pyridoxal enzymes-catalyzed reaction proceeds on only one side of the planar PLP-substrate complex. However, in the amino acid racemase... 

Establishing the inhibition patterns in an enzyme-catalyzed reaction is usually an important step in elucidating the reaction mechanism. One complication in the interpretation of such data is the possible formation of dead-end complexes (i.e., a complex of the form EAP in the above scheme). This is especially important in rapid-equilibrium reactions [ones in which all steps except the rate constants for the central isomerization step (EAB EPQ in the above example) are very large]. 

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