Glycine transamination

A carboxylic acid, normally excreted in the urine in small amounts. It is a constituent of many urinary tract stones. High levels of oxalic acid are excreted in the urine in the rare inborn error of metabolism, primary hyperoxaluria. In this disorder renal stones composed of oxalate are formed and death results from progressive renal failure. The increase in the urinary excretion of oxalic acid appears to be derived from glycine as a result of deficient glyoxylic acid-glycine transamination. 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

This pyridoxal 5-phosphate-dependent enzyme [EC 2.6.1.4] catalyzes the transamination of glyoxylate from L-glutamate to produce glycine and a-ketoglutarate. 

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... 

Figure 25-5 shows the principal catabolic pathways, as well as a few biosynthetic reactions, of phenylalanine and tyrosine in animals. Transamination to phenylpyruvate (reaction a) occurs readily, and the product may be oxidatively decarboxylated to phen-ylacetate. The latter may be excreted after conjugation with glycine (as in Knoop s experiments in which phenylacetate was excreted by dogs after conjugation with glycine, Box 10-A). Although it does exist, this degradative pathway for phenylalanine must be of limited importance in humans, for an excess of phenylalanine is toxic unless it can be oxidized to tyrosine (reaction b, Fig. 25-5). Formation of phenylpyruvate may have some function in animals. The enzyme phenylpyruvate tautomerase, which catalyzes interconversion of enol and oxo isomers of its substrate, is also an important immunoregulatory cytokine known as macrophage migration inhibitory factor.863...

Located in the peroxisomes of liver, L-alanine-glyoxylate aminotransferase catalyzes the transamination of alanine and glyoxylate to form pyruvate and glycine. A rare inborn error of metabolism manifested as hyperoxaluria is due to a deficiency of this enzyme. 

E. coli (107, 125). The complexes have recently been reviewed (126). It is possible that lipoamide dehydrogenase also functions in the complexes that oxidatively decarboxylate the a-keto acids resulting from the transamination of valine, isoleucine, and leucine but these have proved difficult to resolve (127). Lipoamide dehydrogenase also functions in the pyridoxal phosphate and tetrahydrofolate-dependent oxidative decarboxylation of glycine in the anaerobic bacterium Peptococcus glyci-nophilus. The reaction in which the protein-bound lipoic acid is reduced is very complex and not yet fully understood the ultimate electron acceptor is NAD+ (112,113,128). 

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. 

Salvage operation. Write a balanced equation for the transamination of glyoxylate to yield glycine. 

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