Hydroxymethyltransferase, serine

When the glycine formed by serine bydroxymethyltrtmsfereise is not required for purine synthesis, it undergoes cleavage to carhon dioxide and ammonium, catalyzed by the glycine cleavage system. This is a multienzyme 

a lipoamide-containing eiminomethyltransferase, which acts to oxidize the one-cttrbon fragment to a methylene residue at the expense of reducing lipoamide to the disulfhydryl form  

a methylene-tetrahydrofolate synthesizing enzyme that transfers the one-carbon fragment onto tetreihydrofolate, releasing the nitrogen as ammonium and 

an NAD-dependentflavoprotein, dihydrolipoyl dehydrogenase, that oxidizes disulfhydryl lipoamide back to the disulfide. 

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L-serine glycine + formaldehyde serine hydroxymethyltransferase E. coli 201... 

The metabolism of P-hydroxy-a-amino adds involves pyridoxal phosphate-dependent enzymes, dassified as serine hydroxymethyltransferase (SHMT) (EC 2.1.2.1) or threonine aldolases (ThrA L-threonine selective = EC 4.1.2.5, L-aHo-threonine selective = EC 4.1.2.6). Both enzymes catalyze reversible aldol-type deavage reactions yielding glycine (120) and an aldehyde (Eigure 10.45) [192]. 

Figure28-7. The serine hydroxymethyltransferase reaction. The reaction is freely reversible. (H4 folate, tetrahyd rofolate.)...

Serine. Following conversion to glycine, catalyzed by serine hydroxymethyltransferase (Figure 30—5), serine catabolism merges with that of glycine (Figure 30-6). 

Figure 30-5. Interconversion of serine and glycine catalyzed by serine hydroxymethyltransferase. (H4 folate, tetrahydrofolate.)...

Daly, E. C. Aprison, M. H. (1974). Distribution of serine hydroxymethyltransferase and glycine transaminase in several areas of the central nervous system of the rat. J. Neurochem. 22, 877-85. 

FIGURE 40-3 Glycine cleavage system and some related reactions. Glycine and serine are readily interchangeable. Enzymes (1) Glycine cleavage system (2) and (4) Serine hydroxymethyltransferase (3) N5 10-methylenetetrahydrolate reductase. N5 I0-CH2-FH4, N5>10-methylenetetrahydrolate FH4, tetrahydrofolic acid. 

A. Artigues, H. Farrant, V. Schirch, Cytosolic Serine Hydroxymethyltransferase. Deamidation of Asparaginyl Residues and Degradation in Xenopus laevis Oocytes , J. Biol. Chem. 1993, 268, 13784-13790. 

M. L. Di Salvo, S. Delle Fratte, B. Maras, F. Bossa, H. T. Wright, V. Schirch, Deamidation of Asparagine Residues in a Recombinant Serine-Hydroxymethyltransferase , Arch. Biochem. Biophys. 1999, 372, 271-279. 

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,... 

Saraiva LM, Vicente JB, Teixeira M (2004) The role of the flavodiiron proteins in microbial nitric oxide detoxification. Adv Microb Physiol 49 77-129 Schirch V, Szebenyi DME (2005) Serine hydroxymethyltransferase revisited. Curr Opin Chem Biol 9 482-487... 

In the laboratory, serine hydroxymethyltransferase will catalyze the conversion of threonine to glycine and acetaldehyde in one step, but this is not a significant pathway for threonine degradation in mammals. 

The enzyme serine hydroxymethyltransferase requires pyridoxal phosphate as cofactor. Propose a mechanism for the reaction catalyzed by this enzyme, in the direction of serine degradation (glycine production). (Hint See Figs 18-19 and 18-20b.)... 

RGURE 22-44 Conversion of dUMP to dTMP by thymidylate synthase and dihydrofolate reductase. Serine hydroxymethyltransferase is required for regeneration of the /V5,/V10-methylene form of tetrahy-... 

Side chain cleavage (Group c). In a third type of reaction the side chain of the Schiff base of Fig. 14-5 undergoes aldol cleavage. Conversely, a side chain can be added by (3 condensation. The best known enzyme of this group is serine hydroxymethyltransferase, which converts serine to glycine and formaldehyde.211-21313 The latter is not released in a free form but is transferred by the same enzyme specifically to tetrahydrofolic acid (Eq. 14-30), with which it forms a cyclic adduct. 

A5, A1 °-Methylcnctctrahydrofolate is a hydroxymethyl-group donor substrate for several enzymes and a methyl-group donor substrate for thymidylate synthase (fig. 10.15). It arises in living cells from the reduction of A5,A10-methenyltetrahydrofolate by NADPH and also by the serine hydroxymethyltransferase-catalyzed reaction of serine with tetrahydrofolate. 

The pyridoxal-5 -phosphate dependent serine hydroxymethyltransferase (SHMT EC 2.1.2.1) in vivo catalyzes the interconversion of L-serine 158 and glycine 149 by transfer of the /1-carbon of L-serine to tetrahydrofolate (THF) by which the activated formaldehyde is physiologically made available as a C,-pool. The reaction is fully reversible and provides a means for the stereoselective synthesis of 158 in vitro from donor 149 and formaldehyde. Economical yields (88-94%) of L-serine have thus been obtained on a multimolar scale using raw cell extracts of recombinant Klebsiella aerogenes or E. coll in a controlled bioreactor at final product concentrations > 450 gl 1 [461,462], Several SHMTs have been purified and characterized from various organisms including animal tissues [463,464], eucaryotic [465] and procaryotic... 

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