Pyruvate from serine

Threonine dehydratase catalyzes the formation of 2-ketobutyrate from threonine, and pyruvate from serine. This assay can be used to examine the reaction in the presence of both substrates. 

Cysteine derives its carbon and nitrogen from serine. The essential amino acid methionine supplies the sulfur, d. Alanine can be derived by transamination of pyruvate. 

D. Both serine and threonine contain a hydroxyl group. Serine dehydratase produces pyruvate and ammonia from serine. Serine can be produced from glucose via the phosphoglyceric acid intermediates of glycolysis thus it is nonessential. Tetrahydrofolate (FH4) reacts with serine to form glycine and TV6, TV10-methylene-FH4. 

Tryptophan synthase (EC 4.1.2.20) normally catalyzes the synthesis of tryptophan from serine by the oc,p elimination-addition reaction outlined in Scheme 5 where X = OH and Z = indole. The B protein of the oligomeric enzyme will catalyze the dehydration of serine, and in the presence of PLP and mercaptoethanol, the intermediate 15 will form adduct 25. This will then react as in Scheme 9 to yield the ketoacid 26 and pyridoxamine-phosphate 6. The net transamination has been shown to involve protonation at the 4 -Si face in yielding PMP (30). When the apoenzyme of tryptophan synthase is reconstituted with the unnatural substrates (4 / )- or (4 S)-[4- H,]pyridox-amine-phosphate and indole-3-pyruvic acid, an unnatural transamination... 

In this way, a variety of further amino acids are produced, e.g. alanine from pyruvic acid, serine from hydroxyl pyruvic acid and aspartic acid from oxaloacetic acid, as well as phenylalanine and tyrosine from phenylpyruvic acid and 4-hydroxyphenylpyruvic acid respectively. 

The major pathway of serine catabolism probably is by way of its enzymatic dehydration and subsequent spontaneous deamination to yield pyruvic acid (see Fig. 2). An evidence for this is the observation of Lien and Greenberg that alanine is the major amino acid formed from serine-3-C by liver mitochondrial preparations. The alanine could be fomed from the pyruvic acid by transamination. 

Pyridoxal phosphate has been established as a coenzyme in two reactions involving tryptophan. An enzyme has been isolated from Neurospora which catalyzes a synthesis of tryptophane from serine and indole. This reaction requires pyridoxal phosphate. An enzyme has been isolated from E. coli which causes the decomposition of tryptophan to pyruvic acid, indole, and ammonia here too pyridoxal phosphate is a necessary cofactor. 

It was also shown that thialysine may be acetylated on the terminal amino group by some microrganisms(9-11) Thialysine may be cleaved non enzymatically by pyridoxal phosphate through an a- elimination giving cysteamine, ammonia and pyruvate(12). It has to be recalled that thialysine may be synthesized from serine and cysteamine by yeast serine sulfhydrase(15) ... 

As shown on p. 168j, serine can be converted to pyruvate (elimination of water forms the unsaturated amino acid which goes via the imino acid to the a-keto acid) as well as hydroxypyruvate or phosphoserine. The phosphorylated form, which could also come from 3-phosphoglycerate, occurs in a few proteins and phospha-tides (Chapt. XIII). Other bases present in the phosphatides, i.e. ethanolamine and choline, also originate from serine. 

Non-essential amino acids are those that arise by transamination from 2-oxoacids in the intermediary metabolism. These belong to the glutamate family (Glu, Gin, Pro, Arg, derived from 2-oxoglutarate), the aspartate family (only Asp and Asn in this group, derived from oxaloacetate), and alanine, which can be formed by transamination from pyruvate. The amino acids in the serine family (Ser, Gly, Cys) and histidine, which arise from intermediates of glycolysis, can also be synthesized by the human body. 

This enzyme [EC 4.1.99.1], also known as L-tryptophan indole-lyase, catalyzes the hydrolysis of L-tryptophan to generate indole, pyruvate, and ammonia. The reaction requires pyridoxal phosphate and potassium ions. The enzyme can also catalyze the synthesis of tryptophan from indole and serine as well as catalyze 2,3-elimination and j8-replacement reactions of some indole-substituted tryptophan analogs of L-cysteine, L-serine, and other 3-substituted amino acids. 

Difluoroserine is unstable, but some O- and A -protected derivatives of ethyl difluoro-serinate have been prepared. As for trifluoroalanine, a good precursor is ethyl trifluoro-pyruvate. Synthesis is based on the addition of an alcohol on gem-difluoroenamine, resulting from the reductive cleavage of a C—F bond of an imine of ethyl trifluoro-pyruvate (cf. Chapter 2) (Figure 5.10). ... 

Now let us consider the further conversion of PEP and of the triose phosphates to glucose 1-phosphate, the key intermediate in biosynthesis of other sugars and polysaccharides. The conversion of PEP to glucose 1-P represents a reversal of part of the glycolysis sequence. It is convenient to discuss this along with gluconeogenesis, the reversal of the complete glycolysis sequence from lactic acid. This is an essential part of the Cori cycle (Section F) in our own bodies, and the same process may be used to convert pyruvate derived from deamination of alanine or serine (Chapter 24) into carbohydrates. 

---