5 - epimerases

Isotnerases. These catalyse the structural or geometric changes within a molecule. The division includes racemases, epimerases, cis-rran -isomerases, lautomerases and mulases. 

FIGURE 23.31 The phosphopentose epimerase reaction interconverts ribulose-5-P and xylulose-5-phosphate. The mechanism involves an enediol intermediate and occurs with inversion at C-3. 

D-Methylmalonyl-CoA, the product of this reaction, is converted to the L-isomer by methylmalonyl-CoA epunerase (Figure 24.19). (This enzyme has often and incorrectly been called methylmalonyl-CoA racemase. It is not a racemase because the CoA moiety contains five other asymmetric centers.) The epimerase reaction also appears to involve a carbanion at the a-position (Figure 24.20). The reaction is readily reversible and involves a reversible dissociation of the acidic a-proton. The L-isomer is the substrate for methylmalonyl-CoA mutase. Methylmalonyl-CoA epimerase is an impressive catalyst. The for the proton that must dissociate to initiate this reaction is approximately 21 If binding of a proton to the a-anion is diffusion-limited, with = 10 M sec then the initial proton dissociation must be rate-limiting, and the rate constant must be... 

The turnover number of methylmalonyl-CoA epimerase is 100 sec and thus the enzyme enhances the reaction rate by a factor of 10. ... 

FIGURE 24.20 The methylmalonyl-CoA epimerase mechanism involves a resonance-stabilized carbanion at the oj-position. 

Galactose, one of the eight essential monosaccharides (Section 25.7), is biosynthesized from UDP-glucose by galactose 4-epimerase, where UDP = uridylyl diphosphate (a ribonucleotide diphosphate Section 28.1). The enzyme requires NAD+ for activity (Section 17.7), but it is not a stoichiometric reactant. and NADH is not a final reaction product. Propose a mechanism. 

Conversion to penicillin N is achieved by an epimerase that converts the L configuration amino group into the D configuration. 

Thus, in the case of penicillin N, we may not have to add a special precursor providing an active epimerase was present. 

Ribulose 5-phosphate is the substrate for two enzymes. Ribulose 5-phosphate 3-epimerase alters the configuration about carbon 3, forming another ketopentose, xylulose 5-phosphate. Ribose 5-phosphate ketoisom-erase converts ribulose 5-phosphate to the corresponding aldopentose, ribose 5-phosphate, which is the precursor of the ribose required for nucleotide and nucleic acid synthesis. Transketolase transfers the two-carbon... 

The core proteins of DS-PG I and DS-PG II are homologous to those of CS-PG I and CS-PG II found In bone (Table 48-9). A possible explanation Is that osteoblasts lack the epimerase required to convert glucuronic acid to Iduronic acid, the latter of which Is found In dermatan sulfate. 

The GAGs are synthesized by the sequential actions of a battery of specific enzymes (glycosyltransferases, epimerases, suhotransferases, etc) and are degraded by the sequential action of lysosomal hydrolases. Genetic deficiencies of the latter result in mucopolysaccharidoses (eg, Hurler syndrome). 

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