Glycine catabolic pathways

Fia. 1. Glycine catabolism pathway 1, via serine and pyruvate pathway 2, via glyoxylic acid and formate pathway 3, via the glycine-succinate cycle. 

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 20.15 Interrelationships between the serine and glycine metabolic pathways. FH4-"C" indicates 5,10-methylenetetrahydrofolate. (Adapted from Yoshida T, Kikuchi G. Comparative study on major pathways of glycine and serine catabolism in vertebrate livers. ) Biochem 72 1503-1516, 1972.)...

Ammonium ions are produced by the catabolism of a number of amino acids. Glutamate dehydrogenase is the major source of ammonium ions in the body. Ammonium ions are also produced from the catabolic pathways of serine, histidine, tryptophan, glycine, glutamine, and asparagine. L-Amino acid oxidase and... 

The Catabolic Pathways of Threonine, Glycine, Serine, Cysteine, and Alanine. 

The pathways for the formation of oxalate from glycine, ethanolamine, and ascorbic acid, are shown in Figure 10.41. Apparently, oxalate has no function in the body, nor is It catabolized to carbon dioxide. Oxalate occurs in plants as sodium... 

Threonine can be broken down by two separate pathways. Serine dehydratase catalyzes the conversion of threonine to 2-ketobut ate plus an ammonium ion 2-ketobutyrate is then converted by branched-chain keto add (BCKA) dehydrogenase to propionyl-CoA plus carbon dioxide. Propionyl-CoA catabolism is described later in this chapter. Threonine can also be broken down by a complex that has been suggested to be composed of threonine dehydrogenase and acetoacetone synthase (Tressel et ah, 1986). Here, threonine catabolism results in the production of acetyl-CoA plus glycine. 

The third catabolic route would be by the conversion of the 1 and 2 carbon atoms of serine to glycine with the concomitant producticm of methylene THF from C-3 (reaction 5). The enzyme catalyzing this reaction is serine hydroxymethyltransferase (E.C. 2.1.2.1). It has been found in a number of higher plants and partially purified from tobacco root (Prather and Sisler, 1966) and cauliflower bud (Mazelis and Liu, 1967). The glycine formed can then be degraded by the pathways described above (Section 1I,E). The methylene-THF can be oxidized to the Ai-formyl THF and then to CO2 and THF. This latter reaction has been reported in pea mitochondria by Clandinin and Cossins (1975). 

Reduced activities of carboxylase enzymes can cause a metabolic block of certain substrates and a use of alternative pathways for catabolism. Therefore, 3-hydroxyisovaleric acid and 3-methylcrotonyl glycine are formed consequently to a shunt of 3-methylcrotonyl carboxylase counterbalancing its activity decrease. Marginal biotin deficiency experimentally induced by 20 days of free biotin diets in human increased 3-hydroxyisovaleric acid excretion in urine above the upper limit of normal. The normal urinary excretion of 3-hydroxyisovaleric acid in healthy adults is 112 38 pmol per 24 hours (Mock et al. 1997). This suggests that 3-hydroxyisovaleric acid urinary excretion is a good indicator of marginal biotin deficiency. 

Knowledge of the catabolism of glycine is still incomplete. Possible chemical pathways of its metabolism are shown by the equations of Fig. 1. 

A possible pathway of catabolism is through the action of glycine oxidase, which catalyzes the aerobic oxidation only of glycine and sarcosine to yield glyoxylic acid, according to the following equations ... 

This leads us to another pathway for the catabolism of glycine which must be of very great significance. This is the conversion of glycine to serine (reaction 4). The subsequent fate becomes that of serine, which is discussed in the next section. 

Probable pathways for the catabolism of threonine are shown in Fig. 3. The enzymatic formation of glycine from threonine was first reported by Braunstein and Vilenkina. It has been confirmed by Meltzer and Sprinson and in the laboratories of the writer. - ... 

The demethylation reactions so far outlined take us to dimethylglycine. Nothing concrete is known on the further demethylation of this compound. Since N -betaine has been shown to be converted to labeled glycine the demethylation must go to completion. Similarly the role of sarcosine in the proposed cycle is obscure. In feeding experiments sarcosine was found not to be an effective methyl donor for choline formation. " This also was observed for the synthesis of methionine from homocysteine with liver slices and homogenates. The oxidation of the sarcosine methyl to formaldehyde, on the other hand, is a very active process and sarcosine oxidase is very widely distributed. This reaction could serve as a pathway for the catabolism of surplus methyl groups in the body. 

In Fig. 2 a scheme is ven for the genetic interrelationB of amino acids, converging toward components of the dicarboxylic acid system. The scheme includes all amino acids with the exception of valine, leucine and isoleucine, capable of slow transamination, and of glycine and tryptophan, which are catabolized by independent pathways. 

Glycine is utilized in numerous synthetic processes such as the formation of purines, porphyrins, creatine, ethanolamine, choline, and glutathione. These reactions are discussed in other chapters of this work. This section is devoted to a narration of the pathways of catabolism of glycine. 

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