Serine glycine conversion

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

Serine, glycine, and cysteine are dispensable (or nonessential) amino acids because they can be biosynthesized from precursors that are readily available in the body Serine can be made from or converted back to glucose, and also is used in the synthesis of cysteine. The pathways for these conversions are detailed in Chapter 8. 

Folate (foUc acid) is an essential vitamin which, in its active form of tetrahydrofolate (THF, Figure 4-1), transfers 1-carbon groups to intermediates in metaboUsm. Folate plays an important role in DNA synthesis. It is required for the de novo synthesis of purines and for the conversion of deoxyuridine 5-monophosphate (dUMP) to deoxythymidine 5 -monophosphate (dTMP). Additionally, folate derivatives participate in the biosynthesis of choline, serine, glycine, and methionine. However, in situations of folate deficiency, symptoms are not observed from the lack of these products as adequate levels of chohne and amino acids are obtained from the diet. (See also Case 3.)... 

On the other hand, the equilibrium constant K indicates the tendency to form helical or nonhelical states. K values in excess of unity denote helix formers K values much less than unity, conversely, indicate coil-forming sequences. With proteins, proline, serine, glycine, and aspartine, for example, are typical helix breakers. Lysine, thyrosine, aspartic acid, threonine, arginine, cysteine, and phenyl alanine act as neither helical breakers or formers, whereas all other a-amino acids are typical helix formers. 

Asquith and Rivett (72) irradiated tryptophan in oxygenated aqueous solution with a medium pressure mercury lamp under neutral, acidic and basic conditions and identified several degradation products including formylkynurenine, kynurenine, aspartic acid, serine, glycine, alanine and (3-alanine. They suggest that the main degradative pathway of tryptophan is conversion to kynurenine via the indolenine hydroperoxide (see Section III. 1.1). The formation of amino acids could arise from further degradation of kynurenine as shown below. 

It plays a vital role in various intracellular reactions e.g. conversion of serine to glycine, synthesis of thymidylate, synthesis of purines, histidine metabolism etc. Due to folic acid deficiency these reactions are affected. 

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. 

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. 

Conversely, ester condensation reactions join acyl groups from CoA derivatives to Schiff bases derived from glycine or serine. Succinyl-CoA is the acyl donor... 

Glycine is then transported to the mitochondrial matrix where the conversion of two glycines to one serine occurs with the loss of CO2 and NH3 from the pool of fixed molecules. The serine is transported into the peroxisome, where it is deaminated to glycerate. The glycer-ate is transported back to the chloroplast, where it is phosphorylated to 3-phosphoglycerate for the Calvin-Benson cycle. 

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-... 

Thus, one-carhon units at each of the three oxidation levels are utilized in biosyntheses. Furthermore, tetrahydrofolate serves as an acceptor of one-carbon units in degradative reactions. The major source of one-carhon units is the facile conversion of serine into glycine, which yields N lO-methylenetetrahydrofolate. Serine can he derived from 3-... 

The price of methylation. Write a balanced equation for the synthesis of TMP from dUMP that is coupled to the conversion of serine into glycine. 

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. 

M. Watanabe, Y. Morinaga, T, Takenouchi, and H. Enei, Efficient conversion of glycine to L-serine by a glycine-resistant mutant of ahnethylotroph using Co as an inhibitor of L-serine degradation, /. Ferment. Techno., 65 563 (1987). 

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