Serine dehydratase

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Serine dehydratase Enoyl-CoA hydratase Methylglutaconyl-CoA hydratase Cystathionine p-synthase [PLP]... 

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). 

L-Serine dehydratase [EC 4.2.1.13], also known as serine deaminase and L-hydroxyaminoacid dehydratase, catalyzes the pyridoxal-phosphate-dependent hydrolysis of L-serine to produce pyruvate, ammonia, and water. In a number of organisms, this reaction is also catalyzed by threonine dehydratase. 

D-Serine dehydratase [EC 4.2.1.14], also known as d-hydroxyaminoacid dehydratase, catalyzes the pyridoxal-... 

SERINE DEHYDRATASE SERINE DEHYDROGENASE SERINE HYDROXYMETHYLTRANSFERASE SERINE PALMITOYLTRANSFERASE Serine deaminase... 

SERINE DEHYDRATASE SERINE DEHYDRATASE SERINE DEHYDROGENASE Serine esterase inhibitor, irreversible, PHENYLMETHYLSULFONYL FLUORIDE SERINE HYDROXYMETHYLTRANSFERASE SERINE PALMITOYLTRANSFERASE Serine protease inhibitor, irreversible, PHENYLMETHYLSULFONYL FLUORIDE Serine proteinase inhibitor,... 

Serine can be converted to glycine and N5,N10-methylenetetra-hydrofolate (Figure 20.6A). Serine can also be converted to pyru vate by serine dehydratase (Figure 20.6B). [Note The role of tetrahydrofolate in the transfer of one-carbon units is presented on p. 265.]... 

The role of the iron-sulfur clusters in many of the proteins that we have just considered is primarily one of single-electron transfer. The Fe-S cluster is a place for an electron to rest while waiting for a chance to react. There may sometimes be an associated proton pumping action. In a second group of enzymes, exemplified by aconitase (Fig. 13-4), an iron atom of a cluster functions as a Lewis acid in facilitating removal of an -OF group in an a,P dehydration of a carboxylic acid (Chapter 13). A substantial number of other bacterial dehydratases as well as an important plant dihydroxyacid dehydratase also apparently use Fe-S clusters in a catalytic fashion.317 Fumarases A and B from E. coli,317 L-serine dehydratase of a Pepto-streptococcus species,317-319 and the dihydroxyacid... 

L-Serine is converted to pyruvate + NH3 by serine dehydratase (deaminase) in a PLP-dependent reaction. However, using the same coenzyme selenocysteine is converted by selenocysteine lyase into L-alanine + elemental selenium Se°. l-Cysteine may be converted by PLP-dependent enzymes into wither H2S or into S° for transfer into metal clusters. Compare the chemical mecha-... 

The product of certain elimination reactions, e.g., that of serine dehydratase (Chapter 2, equation 2.47), is structure 9.14. 

The substrates of serine dehydratase [45,46] and dihydroxyacid dehydratase [47] differ from citrate in more than just R. The different substrates are compared in Figure 4. They all have in common the central HO —C—CH COO- fragment, indicating that all enzymes should have the following features ... 

As with fumarase, the reactions catalyzed by serine dehydratase and dihydroxyacid dehydratase do not require release and rebinding of intermediate. The reaction mechanisms should be describable as adapted versions of one-half only of Figure 3. 

Answer The mechanism is identical to that for serine dehydratase (see Fig. 18-20a, p. 693) except that the extra methyl group of threonine is retained, yielding a-ketobutyrate instead of pyruvate. 

Pyridoxal phosphate catalyzes the conversion of D-serine dehydratase to pyruvic... 

This reaction is readily reversible. Another means of metabolizing serine, which accounts for its glucogenic character, as well as that of glycine, is the conversion of serine to pyruvate, as indicated in Figure 20.12. This reaction is catalyzed by serine dehydratase. A similar enzyme, threonine dehydratase, converts threonine to a-ketobutyrate, and the latter is then converted to propionyl-CoA, as indicated in Figure 20.13. Another similar enzyme, cysteine desulfhydrase, con-... 

A similar stereochemical question as in the /8-replacement reactions can be asked in the a, /8-eliminations where the group X is replaced by a hydrogen, i.e., is the proton added at C-/8 of the PLP-aminoacrylate on the same face from which X departed or on the opposite face This question has been answered for a number of enzymes which generate either a-ketobutyrate or pyruvate as the keto acid product. Crout and coworkers [119,120] determined the steric course of proton addition in the a,/8-elimination of L-threonine by biosynthetic L-threonine dehydratase and of D-threonine by an inducible D-threonine dehydratase, both in Serratia marcescens. Either substrate, deuterated at C-3, was converted in vivo into isoleucine, which was compared by proton NMR to a sample prepared from (3S)-2-amino[3-2H]butyric acid. With both enzymes the hydroxyl group at C-3 was replaced by a proton in a retention mode. Although this has not been established with certainty, it is likely that both enzymes, like other bacterial threonine dehydratases [121], contain PLP as cofactor. Sheep liver L-threonine dehydratase, on the other hand, is not a PLP enzyme but contains an a-ketobutyrate moiety at the active site [122], It replaces the hydroxyl group of L-threonine with H in a retention mode, but that of L-allothreonine in an inversion mode [123]. Snell and coworkers [124] established that the replacement of OH by H in the a, /8-elimination of D-threonine catalyzed by the PLP-containing D-serine dehydratase from E. coli also proceeds in a retention mode. They... 

The presence of enamine intermediates is especially prominent in some of the elimination reactions catalyzed by the coenzyme, as exemplified by the reaction of serine dehydratase, an enzyme that performs a / -elimination process (Scheme 14). 

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). 

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