Serine transamination

Fig. 39.1. Overview of the synthesis of the nonessential amino acids. The carbons of 10 amino acids may be produced from glucose through intermediates of glycolysis or the TCA cycle. The 11th nonessential amino acid, tyrosine, is synthesized by hydroxylation of the essential amino acid phenylalanine. Only the sulfur of cysteine comes from the essential amino acid methionine its carbons and nitrogen come from serine. Transamination (TA) reactions involve pyridoxal phosphate (PLP) and another amino acid/a-keto acid pair.

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Serine. Oxidation of the a-hydroxyl group of the glycolytic intermediate 3-phosphoglycerate converts it to an 0x0 acid, whose subsequent transamination and dephosphorylation leads to serine (Figure 28—5). 

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. 

Problem 21.5 (a) What is the relationship between reactants and products in the transamination reaction (b) Which ketoacid is needed to give (i) alanine (ii) leucine (iii) serine (iv) glutamine (c) Which amino acids cannot be made by transamination 4... 

Pyridoxal phosphate is the coenzyme for the enzymic processes of transamination, racemization and decarboxylation of amino-acids, and for several other processes, such as the dehydration of serine and the synthesis of tryptophan that involve amino-acids (Braunstein, 1960). Pyridoxal itself is one of the three active forms of vitamin B6 (Rosenberg, 1945), and its biochemistry was established by 1939, in considerable part by the work of A. E. Braunstein and coworkers in Moscow (Braunstein and Kritzmann, 1947a,b,c Konikova et al 1947). Further, the requirement for the coenzyme by many of the enzymes of amino-acid metabolism had been confirmed by 1945. In addition, at that time, E. E. Snell demonstrated a model reaction (1) for transamination between pyridoxal [1] and glutamic acid, work which certainly carried with it the implication of mechanism (Snell, 1945). 

The carbon skeletons of six amino acids are converted in whole or in part to pyruvate. The pyruvate can then be converted to either acetyl-CoA (a ketone body precursor) or oxaloacetate (a precursor for gluconeogenesis). Thus amino acids catabolized to pyruvate are both ke-togenic and glucogenic. The six are alanine, tryptophan, cysteine, serine, glycine, and threonine (Fig. 18-19). Alanine yields pyruvate directly on transamination with... 

Four of the amino acids, alanine, aspartate, glutamate, and serine, are formed by the transamination of their corresponding oxoacids. The other nonessential amino acids are then derived from these four amino acids. The syntheses of serine and tyrosine are described below because of either their importance in aspects of metabolism or their clinical significance the synthesis of serine is essential for folic acid metabolism, while deficiencies in the enzymes synthesizing tyrosine can lead to phenylketonuria. 

Transamination Reactions of Other Pyridoxal Phosphate Enzymes Inaddition to theirmainreactions, anumberofpyridoxalphosphate-dependent enzymes also catalyze the half-reaction of transamination. Such enzymes include serine hydroxymethyltransferase (Section 10.3.1.1), several decarboxylases, and kynureninase (Section 8.3.3.2). 

Pyruvate is the entry point of the three-carbon amino acids—alanine, serine, and cysteine—into the metabolic mainstream (Figure 23.22). The transamination of alanine directly yields pyruvate. 

Serine is synthesized from 3-phosphoglycerate, an intermediate in glycolysis. The first step is an oxidation to 3-phosphohydroxypyruvate. This a-ketoacid is transaminated to 3-phosphoserine, which is then hydrolyzed to serine. 

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