Glycine synthesis from serine

Inhibition of the Reductase affects folate metabolism leading to decreased glycine formation from serine and decreased purine synthesis which requires CH3-THF. To facilitate normal cells folinic acid (Leucovorin) is given along with methotrexate. This acid aids normal cells by its conversion to the coenzyme of Thymidyiate S)mthetase, thus bypassing the block. Since the thymidine nucleotide requirements of rapidly proliferating cells are much greater than for quiescent cells folinic acid cannot meet the demands of the cancer cells. 

N5,jV10-Methylenetetrahydrofolate (methylene-THF) is one of the folic acid coenzymes (Sec. 15.7). Note that this reaction is readily reversible, and in fact, net flux is usually in the direction of glycine synthesis. Thus this amino acid can arise from glucose, and it does so via serine. 

These cocnxymes derived from folic acid participate in many imponant reactions, including conversion ofhomocys-Icine to methionine, synthesis of glycine from serine, purine synthesis (C-2 and C-8). and hi.stidine metabolism. 

Directly required for the synthesis of serine from glycine... 

F. J. Grundy T. M. Henkin, Synthesis of Serine, Glycine, Cysteine and Methionine. In In Bacillus subtllls and Its Closest Relatives From Genes to Cells, A. L. Sonenshein, J. A. Hoch, R. Losick, Eds. American Society for Microbiology Press Washington, DC, 2002 pp 245-254. 

The one-carbon groups on FH4 may be oxidized or reduced (see Fig. 40.3) and then transferred to other compounds (see Fig. 40.4 and Table 40.1). Transfers of this sort are involved in the synthesis of glycine from serine, the synthesis of the base thymine required for DNA synthesis, the purine bases required for both DNA and RNA synthesis, and the transfer of methyl groups to vitamin B12. 

A mild and highly efficient one-pot synthesis of aryl glycines 618 from readily available serine derivatives 617 has been reported (Scheme 3.242) [650]. This method is based on the p-fragmentation of a primary alkoxy radical, generated on treatment of the serine derivative with PhI(OAc)2-l2, immediately followed by... 

The equilibrium constant for Eq. (6) is 4.6, slightly in favor of glycine synthesis (Huennekens and Osborn, 1959). There is evidence from bacteria and animals showing that much glycine is made from serine and that serine hydroxymethyltransferase is involved. 

In all reactions, the first stage is formation of SchifTs base a by condensation of PalP and the amino acid. Schiff s bases a and b represent part of transamination, but for the complete mechanism see Transamination. Racemization a- b, followed by b-ia-iamino acid-1-PalP, with addition of the proton in the opposite configuration. Amino acid decarboxylation a -> d- c - amine + PalP. Serine hydroxymethyltransferase (EC 2.1.2.1) X = OH L-serine + PalP a f- g glycine + PalP reversal of these reactions leads to L-serine synthesis from glycine the hydroxymethyl group is carried by te-trahydrofolic acid. Cysteine desulfhydrase (EC 4.4.1.1) X = SH cy eine + PalP a b-> c-y hydro-... 

The formation of glycine from serine has been verified by the manner of its utilization for purine synthesis. ... 

Glycine is another material which is used. These molecules of glycine come from the proteins of the diet, from the degradation of serine or threonine, or are provided by synthesis from pyruvic acid. 

The names serine hydroxymethylase 89) and serine aldolase 34) have been proposed for the enzyme. The basis for the name serine aldolase is that the synthesis of serine is an aldol condensation and that a number of similar enz3une reactions are known, namely, for the decomposition of threonine to acetaldehyde and glycine and of phenylserine to benzaldehyde and glycine. It has been partially pmrified from sheep 34), beef 36), rabbit 35), and chicken 36) livers by standard procedures for protein purification. Extracts of acetone powders of liver have been used mainly as the starting materials. 

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