Enzyme serine racemase

Wolosker, H., Blackshaw, S., Snyder, S. H. Serine racemase a glial enzyme synthesizing D-serine fo regulate glutamate-N-methyl-D-aspartate neurotransmission, Proc. Natl. Acad. Sci. USA 1999,... 

Serine Racemase (EC 5.1.1.16] Serine racemases have been discovered in both bacteria and eukaryotes (for a review see [60, 62). In the latter organisms, serine racemase catalyzing the conversion of L-Ser to D-Ser was at first discovered in the silkworm Bombyx mori it is a PLP-dependent racemase which is also active on L-Ala (-6% of the activity on L-Ser). A serine racemase was also purified from rat brain (and a serine racemase cDNA was cloned from mouse brain). Mammalian serine racemase shows sequence simUarily with L-threonine dehydratase from various sources all the active site residues of the latter enzyme are also conserved in mouse serine racemase. Mammalian serine racemase is a member of the fold-type II group of PLP enzymes (similarly to L-threonine dehydratase, D-serine dehydratase, and so on) and distinct from alanine racemase, which belongs to the fold-type III group. Mouse serine racemase shows a low kinetic efficiency the Km values for L- and D-Ser are -10 and 60 mM, respectively and the V ax values with L- and D-Ser are 0.08 and 0.37 units/mg protein (less than 0.1% of those of alanine racemase on L- and D-Ala, see above). 

Serine racemase. The nervous system contains a substantial amount of d-serine, which is generated from 1-serine by serine racemase, a PLP-dependent enzyme. Propose a mechanism for this reaction. What is the equilibrium constant for the reaction 1-serine d-serine ... 

The presence of o-serine in mammalian brain tissue was first reported in 1989 [33, 34]. It has recently been established that o-serine is employed in the mammalian forebrain as a co-agonist for the N-methyl-o-asparate (NMDA) excitatory amino acid receptor [35, 36]. A PLP-dependent serine racemase has been cloned and purified from mammalian brain, and found to be a homodimer, which has a number of nonessential cofactors that enhance its activity, including Ca +, Mg + and ATP [37-40]. The mouse brain enzyme has also been shown to catalyze elimination from L-serine, to form pyruvate, with an activity comparable to that for racemiza-tion [41]. Interestingly, the first instance of this class of racemase was discovered by Esaki and coworkers in the silkworm, Bombyx mori [42]. o-serine concentration in the blood of B. mori larvae is thought to play a role in metamorphosis. 

Other amino acids such as L-aspartate and L-serine, can spontaneously racemize with aging in humans [149]. It has been reported that microwaving milk racemizes L-proline to D-proline, which could reduce the milk s nutritional value [150]. For L-serine, a serine racemase has been characterized that catalyzes the direct racemization of L-serine to D-serine. This enzyme can also catalyse D-serine to L-serine but with lesser affinity. As a number... 

PLP-dependent enzymes catalyze the following types of reactions (1) loss of the ce-hydrogen as a proton, resulting in racemization (example alanine racemase), cyclization (example aminocyclopropane carboxylate synthase), or j8-elimation/replacement (example serine dehydratase) (2) loss of the a-carboxylate as carbon dioxide (example glutamate decarboxylase) (3) removal/replacement of a group by aldol cleavage (example threonine aldolase and (4) action via ketimine intermediates (example selenocysteine lyase). 

Inhibitors of cell wall mucopeptide synthesis - The antibiotic O-carbamyl-D-serine is a competitive inhibitor of alanine racemase, whereas D-cyclo-serine inhibits both D-alanyl-D-alanine synthetase and alanine racemase, both enzymes being required for synthesis of the peptide moiety of the mucopeptide 1. ... 

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