Glycine degradative pathways

In the third and final pathway of glycine degradation, the achiral glycine molecule is a substrate for the enzyme D-amino acid oxidase. The glycine is converted to glyoxylate, an alternative substrate for hepatic lactate... 

Reorganizes coverage of amino acid degradation to focus on the big picture Adds new material on the relative importance of several degradative pathways Includes a new description of the interplay of the pyridoxal phosphate and tetrahydrofolate cofactors in serine and glycine metabolism... 

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...

FIGURE 10.41 DegrAdative pathways resulting in the foimation of Oxalic acid. The degradation of glycine and ethanolamlne to yield oxalic acid is catalyzed by oxidases. The breakdown of ascorbic add to produce oxalic and threonic acids occurs spontaneously over... 

The presence of another contaminant peak in L-tryptophan implicated in EMS was detected upon HPLC with both UV and FL analyses by Toyo oka et al.9 and was characterized as PAA by Goda et al.7 Adachi et al.15 studied the metabolism of PAA in rats and described four metabolites of PAA in the urine (N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(phenylamino)lactic acid, and 3-(hydroxy-phenylamino)-lactic acid). The results suggested that the degradation pathway of PAA was similar to that of phenylalanine. Other studies with PAA are described in Section 11.10. 

The a-oxoamine synthases family is a small group of fold-type I enzymes that catalyze Claisen condensations between amino acids and acyl-CoA thioesters (Figure 16). Members of this family are (1) 8-amino-7-oxononanoate (AON) synthase (AONS), which catalyzes the first committed step in the biosynthesis of biotine, (2) 5-aminolevulinate synthase (ALAS), responsible for the condensation between glycine and succinyl-CoA, which yields aminolevulinate, the universal precursor of tetrapyrrolic compounds, (3) serine palmitoyltransferase (SPT), which catalyzes the first reaction in sphingolipids synthesis, and (4) 2-amino-3-ketobutyrate CoA ligase (KBL), involved in the threonine degradation pathway. With the exception of the reaction catalyzed by KLB, all condensation reactions involve a decarboxylase step. 

Asquith and Rivett (72) irradiated tryptophan in oxygenated aqueous solution with a medium pressure mercury lamp under neutral, acidic and basic conditions and identified several degradation products including formylkynurenine, kynurenine, aspartic acid, serine, glycine, alanine and (3-alanine. They suggest that the main degradative pathway of tryptophan is conversion to kynurenine via the indolenine hydroperoxide (see Section III. 1.1). The formation of amino acids could arise from further degradation of kynurenine as shown below. 

In the laboratory, serine hydroxymethyltransferase will catalyze the conversion of threonine to glycine and acetaldehyde in one step, but this is not a significant pathway for threonine degradation in mammals. 

There are two significant pathways for threonine degradation. One pathway leads to pyruvate via glycine (Fig. 18-19). The conversion to glycine occurs in two steps, with threonine first converted to 2-amino-3-... 

Threonine is cleaved to acetaldehyde by the same enzyme. A related reaction is indicated in Fig. 24-27 (top). In a more important pathway of degradation of threonine the hydroxyl group of its side chain is dehydrogenated to form 2-amino-3-oxobutyrate which is cleaved by a PLP-dependent enzyme to glycine and acetyl-CoA (Eq. 14-31).214 215... 

Pyridines and pyrroles can be formed in different pathways by Mail-lard reaction. The formation of 5-methyl pyrrole aldehyde and 6-methyl-3-pyridinole has been observed by Nyhammar et al (17) by the reaction of isotope labelled 3-deoxyosone with glycine. The 3-deoxy-hexosone represents an -dicarbonyl compound and in this way the Strecker degradation occurs. Another pathway is the reaction of fu-rans with ammonia. Under roast conditions, we have obtained primarily the corresponding pyrrole, whereas we found the corresponding py-... 

---