Serine synthesis

Lejczak, B., Kafarski, P., Soroka, M., and Mastalerz, P., Synthesis of the phos-phonic acid analog of serine, Synthesis, 577,1984. 

Panizzutti, R., Miranda, J. de, Ribeiro, C. S., Engelender, S., Wolosker, H. A new strategy to decrease N-methyl-D-aspartate (NMDA) receptor coactivation inhibition of D-serine synthesis by converting serine racemase into an eliminase, Proc. Natl. Acad. Sci. USA 2001, 98, 5294-5299. 

D. Serine is synthesized from glucose. The pathway branches from glycolysis at phospho-glyceric acid, which is reduced, transaminated, and dephosphoiylated by phosphoserine phosphatase. Pyruvate kinase is a glycolytic enzyme that functions beyond the branch point for serine synthesis. 

Glycine (aminoacetic acid, aminoethanoic acid) is HjN. CHj.COOH, with = 2.4. It is transaminated by an ala-nine-glyoxylate aminotransferase. The glycine can then be incorporated into proteins and used for serine synthesis or simply be degraded. 

Serine metabolism. The pathways and structures of serine synthesis and degradation are shown. The major pathway of synthesis is presented as well as two pathways for degradation. 

Figure 7 Localization of cell wall synthesis in isogenic pairs of vancomycin-susceptible and vancomycin-resistant Staphylococcus aureus strains. Images show labeling of JH1/JH9 (susceptible) and COL/VM50 (resistant) cells with a fluorescent vancomycin derivative, after growth with an excess of o-serine (synthesis of older peptidoglycan with D-Ala-D-ser termini, to which the labeled vancomycin cannot bind) followed by transient incubation with o-Alanine, which results in n-Ala incorporation into new peptidoglycan, to which the vancomycin can bind. In all cases, the main location for cell wall synthesis is at the division septum. Data reproduced from P. M. Pereira S. R. Filipe A. Tomasz M. G. Pinho, Antimicrob. Agents Chemother. 2007, 51 (10), 3627, with permission from the American Society for Microbiology.

In the biosynthesis of serine from glucose, 3-phosphoglycerate is first oxidized to a 2-keto compound (3-phosphohydroxypyruvate), which is then transaminated to form phosphoserine (Fig. 39.5). Phosphoserine phosphatase removes the phosphate, forming serine. The major sites of serine synthesis are the liver and kidney. 

Regulatory mechanisms maintain serine levels in the body. When serine levels fall, serine synthesis is increased by induction of 3-phosphoglycerate dehydrogenase and by release of the feedback inhibition of phosphoserine phosphatase (caused by higher levels of serine). When serine levels rise, synthesis of serine decreases because synthesis of the dehydrogenase is repressed and the phosphatase is inhibited (see Fig. 39.5). 

Fig. 39.5. The major pathway for serine synthesis from glucose is on the left, and for serine degradation on the right. Serine levels are maintained because serine causes repression (circled 4-) of 3-phosphoglycerate dehydrogenase synthesis. Serine also inhibits (circled -) phosphoser-ine phosphatase.

Many plant tissues contain hydroxypyruvate reductase (o-glycerate dehydrogenase) but it is especially active in leaves (Stafford et al., 1954 Stafford and Magaldi, 1954). Tolbert et al. (1970) purified the spinach enzyme and investigated its properties. It catalyzes reduction of hydroxypyruvate to D-glyceric acid by NADH [Eq. (3)]. Although the equilibrium is toward glyceric acid rather than hydroxypyruvate, the presence of sufficient amino donor and an appropriate transaminase would allow serine synthesis by the nonphosphorylated pathway with Eq. (3) as an intermediate step. 

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-... 

Ellegard, J., Esmann, V. and Henriksen, L. (1972) Deficient folate function during treatment of psoriasis with methotrexate diagnosed by determination of serine synthesis in lymphocytes, Brit. J. Dermat., 87 248. 

In addition, incomplete oxidation of polyols leads to production of higher valued chemicals, such as dihydroacetone, which is a valuable tanning agent, hydroxypyruvic acid, which is a flavor component and a possible starting material for DL-serine synthesis, and tartronic and mesoxalic acids, which are important intermediates for novel polymer and pharmaceutical synthesis. Therefore, research on cogeneration of electricity and higher valued chemicals from polyols... 

In the light in the leaves of C3 plants, the major role of serine metabolism is in photorespiration. However, serine can also act as a precursor of cysteine. There is therefore a requirement for serine synthesis through a route not related to photorespiration. Shingles etal. (1984) were able to show that chloroplasts had the capacity to convert formate and glycine to serine, provided that they were supplied at high concentrations. Kleczkowski and Givan (1988) have discussed in detail other potential routes of serine synthesis. 

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