Stereochemical specificity, enzyme

Stereochemical specificity, in which the enzyme catalyzes reactions of only one stereoisomer of a compound. 

When a racemic substance is hydrogenated or when the reduction leads to the production of centers of asymmetry, the phytochemical reduction will take at first a completely or partially asymmetric course. Examples of such asymmetric reactions are the conversions of pure racemic valeraldehyde, acetaldol, furoin and furil, diacetyl and acetyl-methylcarbinol to optically active alcohols. Occasionally meso forms also arise, as for example in the case off glycols (p. 84). The reasons for the stereochemical specificity of these reactions have not been clarified. This type of phenomenon has frequently been observed in the related intramolecular dismutation of keto aldehydes, especially if enzyme materials of differing origins are used. 

Transketolase catalyzes the reversible transfer of a hydroxyacetyl fragment from a ketose to an aldehyde. Because the ketose products formed by transketolase reactions are not acceptors for a consecutive transformation by the same enzyme, we have investigated the option to include a xylose (glucose) isomerase (Xyll E.C. 5.3.1.5), which has similar stereochemical specificity, for ketose to aldose equilibration (Scheme 2.2.5.13). Starting from racemic lactaldehyde 32a, the transketolase forms 5-deoxy-D-xylulose 35a, which indeed was accepted by the Xyll in situ for diastereospecific conversion into 5-deoxy-D-xylose 36a. The latter again proved to be a substrate of transketolase which completed a tandem operation to furnish 7-deoxy-sedoheptulose 37a as the sole bisadduct in 24% overall yield and in enantio- and diastereomerically pure quality [35, 36]. All four stereocenters of the resulting product are completely controlled by the enzymes during this one-pot operation. The procedure profits from the limited tolerance of the isomerase... 

Problem 21.51 Account for the stereochemical specificity of enzymes with chiral substrates. 

The stereochemical specificity of enzymes depends on the existence of at least three different points of interaction, each of which must have a binding or catalytic function. A catalytic site on the molecule is known as an active site or active centre of the enzyme. Such sites constitute only a small proportion of the total volume of the enzyme and are located on or near the surface. The active site is usually a very complex physico-chemical space, creating micro-environments in which the binding and catalytic areas can be found. The forces operating at the active site can involve charge, hydrophobicity, hydrogen-bonding and redox processes. The determinants of specificity are thus very complex but are founded on the primary, secondary and tertiary structures of proteins (see Appendix 5.1). 

Further progress on the problem of the stereochemical specificity of cyclitol oxidation by A. suboxydans will depend on the isolation of the enzyme or enzymes involved. Cell-free preparations capable of oxidizing wn/o-inositol have been obtained,43 44 but these have not been further purified. The enzyme is apparently a true dehydrogenase, since it can couple with diaphorase.44... 

As discussed in Chapter 9, many enzymes display stereochemical specificity. Clearly, the enzymes of sucrose synthesis are able to distinguish between the isomers of the substrates and link only the correct pair. 

Due to all of these features, stereochemical specificity has been described as a very deep evolutionary trait . It is very difficult to transform an enzyme binding site for a D-isomer to that for an L-isomer. Such changes might be compared to changing the action of the tail flukes of a whale (horizontally mounted) to those of... 

Enzymes are stereochemically specific that is, they often convert only one stereoisomeric form of substrate into product. Why is such specificity inherent in their structure ... 

Stereochemical studies have shown that the addition to the methyl carbon adjacent to the carbonyl group takes place with inversion of relative configuration (12-15). While most enzyme are specific for the si face of the carbonyl group of oxaloacetate, some bacterial citrate synthases react at the re face. The facial selectivity therefore does not have any mechanistic significance, since it is inconsistent, but the substitution pattern at carbon may indicate an evolved feature based on mechanistic advantage (16). 

Enzymes are also classified on the basis of their specificity. The four classifications of specificity are absolute, group, linkage, and stereochemical specificity. An enzyme with absolute... 

Stereochemical specificity—an enzyme distinguishes one enantiomer from another. 

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