Serine formation from glycine

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 catabolism of glycine by way of serine and pyruvic acid is probably of little quantitative significance. This is indicated by the low degree of acetoacetate formation from glycine and serine in liver slices in contrast to the formation of acetoacetate from lactate SO). Furthermore, it is probable that serine serves as a source of glycine in the organism rather than the reverse. This is discussed under serine biosynthesis in Chapter 15. 

Figure 23.22. Pyruvate Formation from Amino Acids. Pymvate is the point of entry for alanine, serine, cysteine, glycine, threonine, and tryptophan.

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. 

Solid-state CPMAS spectrum of the fibroin prepared from cocoons spun by larvae fed with [ C]formate revealed that serine C3 was labelled specifically with C, suggesting that the reverse conversion from glycine into serine took place in the silkworm. " ... 

Application of this inhibitor to pea leaves (Miflin et al., 1966) caused glycine, but not glycolate to accumulate. Also, addition of nonradioactive glyoxylate with radioactive glycine stimulated rather than inhibited radioactive serine formation. It was suggested by Miflin et al. (1966), therefore that serine was formed from two molecules of glycine by a mechanism similar to that already known in bacteria and in avian liver [Eq. (4)]. 

Ohba and co-workers have demonstrated that A -protected a-amino esters are compatible with the Schollkopf oxazole synthesis cf., 38->39). In the case of ammo esters derived from natural amino acids (e.g., 38), the presence of an additional acidic N-H bond in the AABoc ester substrate necessitated the use of an added excess of metalated isocyanide (2.5 equiv was found to be optimal) to obtain maximal yields. Under optimized conditions, oxazoles (39) were obtained in good yield from iV-Boc glycine, alanine, and phenylalanine. Oxazole formation from iV-Boc serine (which possesses an additional acidic site in its hydroxylic side chain) proceeded in good yield (66%) using 3.5 equiv lithiated methyl isocyanide. Notably, no epimerization was detected in the reaction of N-Boc alanine methyl ester with lithiated methyl or ethyl isocyanide under these conditions. Minor epimerization was observed (91-92% ee product) with substrates that lacked a carbamate NH hydrogen e.g., A -Boc proline methyl ester), however. ... 

Serine-Glycine Interconversion. Feeding experiments in animals showed the formation of glycine from serine and threonine. An interconveision of serine and glycine was indicated by microbial nutritional experiments and confirmed by isotope experiments with both microbial and animal preparations. The carboxyl and a-carbon of serine are converted to gly-... 

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

The serine is synthesized from formate and glycine. If the formate is tagged with and the carboxyl of the glycine with C , doubly-labelled serine is obtained ... 

Most research on the effect of folate deficiency on lymphoid cell metabolism has focused on the enzymes involved in pyrimidine synthesis. Defective interconversion of glycine and serine has been reported in peripheral lymphocytes from folate deficient patients due to folate malabsorption, malnutrition or treatment with phenytoin (Ellegaard and Esmann, 1972), methotrexate, (Ellegaard and Esmann, 1973). In fact estimation of serine formation in lymphocytes cultured with glycine and labeled formate is the basis for the test developed to detect early folate deficiency before the appearance of megaloblastic changes in the bone marrow and low RBC folate levels (Ellegaard and Esmann, 1973). 

The formation of glycine from serine was first shown by Shemin (22). By labeling the carboxyl carbon of serine with and the amino nitrogen with... 

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