Glycine transaminase

Daly, E. C. Aprison, M. H. (1974). Distribution of serine hydroxymethyltransferase and glycine transaminase in several areas of the central nervous system of the rat. J. Neurochem. 22, 877-85. 

Glycine Glycine transaminase Glyoxylate Primary oxaluria type 1 Renal failure due to stone formation... 

Many of the transaminase reactions are linked to the amination of 2-oxo-glutarate to glutamate or glyoxylate to glycine, which are substrates for oxidative deamination, reforming the oxo-acids, and thus providing a pathway for net deamination of most amino acids. 

To solve this problem, we used a mimic of a different enzyme, diaUcylglycine decarboxylase (30). In this enzyme, pyridoxal phosphate reacts with an alpha-disubstituted glycine to perform an irreversible decarboxylation (Fig. 6) while converting the pyridoxal species to a pyridoxamine. We imitated this with our model transaminations using pyridoxal species that carry hydrophobic chains, and we were able to achieve as many as 100 catalytic turnovers. Thus, we could imitate one enzyme—the ordinary transaminases—by also imitating another enzyme that solved the turnover problem. 

Figure 6 The mechanism used in the oxidative decarboxylation of alpha disubstituted glycines by an enzyme, which, in mimics, solved the problem of converting pyridoxal species to pyridoxamine species in biomimetic transaminase systems.

Tn amino acid production, we encounter an important problem in bio.synthesis—namely, stereochemical control. Because all amino acids except glycine are chiral, biosynthetic pathways must generate the correct isomer with high fidelity. In each of the 19 pathways for the generation ofchiral amino acids, the stereochemistry at the a-carbon atom is established by a transamination reaction that includes pyridoxal phosphate (PEP). Almost all the transaminases that catalyze these reactions descend from a common ancestor, illustrating once again that effective solutions to biochemical problems are retained throughout evolution. 

The Stickland reaction (47) has received much attention as a possible route to chiral acetate due to the availability of chiral glycine (48). In the Stickland reaction two moles of glycine and one mole of d-alanine are converted quantitatively into three moles of acetate, three moles of ammonia, and one mole of C02 by the organism Clostridium sticklandii. The presence of amino acid transaminase in the intact organisms leads to extensive hydrogen exchange although in the purified enzyme the replacement of NH2 by H occurs stereospecifically with inversion (49, 50). Unfortunately, the rates of conversion with the purified enzyme are too low to be synthetically useful. 

Oxalate, produced from glycine or obtained from the diet, forms precipitates with calcium. Kidney stones (renal calculi) are often composed of calcium oxalate. A lack of the transaminase that can convert glyoxylate to glycine (see Fig 39.6) leads to the disease primary oxaluria type I (PH 1). This disease has a consequence of renal failure attributable to excessive accumulation of oxalate in the kidney. 

Tryptophan 331 is converted to tryptamine 332 by both aromatic L-amino acid decarboxylase (EC 4.1.1.28) and tyrosine decarboxylase (EC 4.1.1.25), and in both instances (334, 335) it was shown, either by use of the pro-R specific monoamine oxidase (335) or by degradation of the labeled tryptamines to glycine and use of the pro-S specific D-amino acid oxidase and pro-R specific glutamate pyruvate transaminase (334), that decarboxylation involved retention of configuration. Hydroxylation that leads to sporidesmin 333 has been shown to involve specific loss of the 3-pro-R hydrogen, and so again hydroxylation involves retention of configuration (102). 

It is obvious that AOA can be considered the aminooxy analogue of glycine, while AOPP is the aminooxy analogue of phenylalanine. Both of these compounds can be expected to interfer with amino acid metabolizing enzymes carrying a carbonyl group(e.g. that of pyridoxal phosphate in the case of transaminases or dehydroalanine in... 

The fate of 5-amino levulinic acid is dual. It may be converted to porphobilinogen by a pathway to be described below, or under the influence of a transaminase it may yield a-ketoglutaraldehyde, which in turn produces a-ketoglutarate or succinate (see Fig. 3-50). Thus, 5-amino levulinic acid occupies a key position between the citric acid cycle and the porphyrins biosynthetic pathway. The significance of 5-amino levulinic acid in metabolism is illustrated in Fig. 3-50 showing the metabolic conversions involved in the so-called Shemin succinate glycine cycle. 

Amino acids have been produced by chemical synthesis, extraction from protein hydrolysates, enzymatic synthesis, and microbial fermentation. The chemical synthesis includes artificial synthesis from chemical starting material and usually produces an enantiomeric mixture of amino acids which will further require a step of optical resolution. Only a few amino acids are produced economically by chemical synthesis owing to the high production cost. Glycine and methionine are the two amino acids that are manufactured chemically and widely used in animal feeds. Glycine is manufactured from ammonia and formaldehyde and does not have a stereo chemical center or is achiral. For methionine, animals have a d-amino acid oxidase and transaminase activity that can convert the D form to L form of the amino acid. Otherwise DL methionine is acetylated to produce L-methionine. 

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