Glycine oxidative decarboxylation

Glycine anion (230) is decarboxylated when exposed to hydroxyl radicals. The major initial product is an amino radical cation (231), which suffers rapid 100 ns) fragmentation into CO2 and a carbon-centred radical (232). Oxidative decarboxylation... 

While Tetrahymena must have lipoic acid in its diet, we humans can make our own, and it is not considered a vitamin. Lipoic acid is present in tissues in extraordinarily small amounts. Its major function is to participate in the oxidative decarboxylation of a-oxoacids but it also plays an essential role in glycine catabolism in the human body as well as in plants.295 296 The structure is simple, and the functional group is clearly the cyclic disulfide which swings on the end of a long arm. Like biotin, which is also present in tissues in very small amounts, lipoic acid is bound in covalent amide linkage to lysine side chains in active sites of enzymes 2963... 

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...

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). 

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.

Lysine is formed in bacteria by decarboxylation of meso-diamino-pimelic acid (Fig. 24-14). Glycine is decarboxylated oxidatively in mitochondria in a sequence requiring lipoic acid and tetrahydrofolate as well as PLP (Fig. 15-20). A methionine decarboxylase has been isolated in pure form from a fem. ° The bacterial dialkylglycine decarboxylase is both a decarboxylase and an aminotransferase which uses pyruvate as its second substrate forming a ketone and L-alanine as products (See Eq. 

The GCS catalyzes the reversible oxidative decarboxylation of glycine to CO2, ammonia, and methylene-tetrahydrofolate (THF)7 Unlike the PDC and KDC, the GCS is not a tightly bound multienzyme complex, but a system of four independent proteins (P, H, T, and L) that loosely associate (Figure 5). The homodimeric P-protein, which is equivalent to the Ej subunits of PDC and KDC, catalyzes the pyridoxal 5 -phosphate (PLP)-dependent decarboxylation of glycine, yielding The resulting aminomethyl... 

P-protein Subunit of the glycine cleavage system, which uses pyridoxal 5 -phosphate to catalyze the oxidative decarboxylation of glycine. 

R = H, = Me) and (96 R = Me, R = H) is obtained by oxidative decarboxylation of the bicyclo[4.1.0]hept-3-ene-l,6-dicarboxylic acid (95) with lead tetra-acetate. The amino-acid (97), prepared from C- (o-hydroxyphenyl)glycine and t-butyl azidoformate, cyclizes to the aminobenzofuranone (98) this type of product exhibits chemiluminescence when exposed to oxygen in the presence of a base. Treatment of 2,2 -di(bromomethyl)benzil (99) with potassium t-butoxide results in an unusual intramolecular nucleophilic substitution to give the spiro-compound (100). 

Gunsalus and Sagers (1958), in studying this sequence for C. acidiurici, propose that dissimilation of glycine proceeds either by condensation with FH4 and oxidation of the adduct, or else by way of serine to pyruvate and thence oxidative decarboxylation to acetate and COs. Formate and CO2 are in equilibrium, thus providing another cyclic mechanism for oxidation of Cl units. A similiar reaction sequence is stated to hold for the dissimilation of ycine by the anaerobe Diplococcua glyeinophilus. Glyoxylic acid is inert in these systems. 

A similar success was observed for studies of branched chain ketoaciduria in which the second stage of the catabolism of leucine, valine and isoleucine involves an oxidative decarboxylation. In patients with branched chain ketoaciduria, this step is blocked for all three of these amino acids. The urine of these patients takes on the odour of maple syrup and hence this condition is also known as maple syrup urine disease. H NMR spectroscopy was used to study the urines of patients with such branched chain ketoaciduria. The spectra showed several abnormal metabolites including the amino acids leucine, isoleucine and valine and their corresponding transamination products. It was noted that 2-hydroxyisovalerate levels were very high in the urines of all the patients studied and that, as in other inborn errors of metabolism, the levels of urinary glycine were elevated. 

Minor Pathways. Dihydroxyacetone phosphate can be transformed to glycerol phosphate, which is used for the synthesis of fats and glycerophosphatides. Phosphoglycerate can be converted to 3-phosphohydroxypyruvate and further to hydroxypyruvate. This last compound is possibly related to glycolate (by oxidative decarboxylation) and to glyoxylate, and hence to glycine. Pyruvate is related to alanine by transamination, and hydroxypyruvate, to serine. 

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