Glycine-dependent enzymes

They lead to the formation of one (acetaldehyde and pyruvate dependent enzymes) or two (DHAP- and glycine-dependent enzymes) stereogenic centers. The stereoselectivity usually depends on the enzyme most of the stereoisomers can be obtained by choosing the appropriate enzyme. Especially, glycine and DHAP-dependent enzymes present some stereocomplementary... 

The metabolism of P-hydroxy-a-amino adds involves pyridoxal phosphate-dependent enzymes, dassified as serine hydroxymethyltransferase (SHMT) (EC 2.1.2.1) or threonine aldolases (ThrA L-threonine selective = EC 4.1.2.5, L-aHo-threonine selective = EC 4.1.2.6). Both enzymes catalyze reversible aldol-type deavage reactions yielding glycine (120) and an aldehyde (Eigure 10.45) [192]. 

This FAD-dependent enzyme [EC 1.4.3.3] catalyzes the reaction of a D-amino acid with dioxygen and water to generate an a-keto acid, ammonia, and hydrogen peroxide. Substrate specificity is wide and includes glycine. 

This pyridoxal-phosphate-dependent enzyme [EC 2.3.1.29], also known as glycine C-acetyltransferase and 2-amino-3-ketobutyrate coenzyme A ligase, catalyzes the reaction of acetyl-CoA with glycine to produce coenzyme A and 2-amino-3-oxobutanoate. 

This pyridoxal-phosphate-dependent enzyme [EC 2.6.1.4] catalyzes the reaction of glycine with a-ketoglu-tarate (or, 2-oxoglutarate) to produce glyoxylate and l-glutamate. See also GlycineiOxaloacetate Aminotransferase Glyoxylate Aminotransferase A. E. Braunstein (1973) The Enzymes, 3rd ed., 9, 379. 

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. 

This FMN-dependent enzyme [EC 1.5.99.1] catalyzes the reaction of sarcosine with an acceptor and water to produce glycine, formaldehyde, and the reduced acceptor. 

This pyridoxal-phosphate-dependent enzyme [EC 2.1.2.1], which has a recommended EC name of glycine hydroxymethyltransferase, catalyzes the reversible reaction of 5,10-methylenetetrahydrofolate with glycine and water to produce tetrahydrofolate and L-serine. The enzyme will also catalyze the reaction of glycine with acetaldehyde to form L-threonine as well as with 4-tri-methylammoniobutanal to form 3-hydioxy-N, N, N -trimethyl-L-lysine. 

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... 

Continuing the folate cycle, THF reacts with serine to produce 5,10-methylenetetrahydrofolate, a reaction catalyzed by the vitamin B6-dependent enzyme serine/glycine hydrox-ymethyltransferase. 

ALA synthase is a pyridoxal phosphate-dependent enzyme and promotes Schiff-base formation between its coenzyme and glycine (67 in Fig. 37). Nucleophilicity at C-2 of the glycine could be generated either by decarboxylation or by abstraction of a proton. In the first case 5-aminolaevulinic acid would retain both methylene protons of glycine, in the second, one of the protons would be lost to the medium (Fig. 37). Acylation of the pyridoxal-bound intermediate (68 or 69) by succinyl-CoA would constitute the next step and this could be followed either by direct hydrolysis of the Schiff-base or by decarboxylation with subsequent hydrolysis depending on which course was chosen in the first stage of the reaction. 

The glycine-dependent aldolases are pyridoxal 5-phosphate dependent enzymes that catalyze the reversible aldol reaction, where glycine and an acceptor aldehyde form a (i-hydroxy-a-amino acid (Scheme 5.47).74 Serine hydroxymethyltransferases, SHMT (EC 2.1.2.1), and threonine aldolases, two types of glycine dependent aldolases, have been isolated. In... 

Synthesis of the porphyrin involves the integration between the mitochondrion and cytosol, as in a number of metabolic processes previously examined such as urea synthesis, gluconeogenesis, and some amino-acid catabolism. The first step is mitochondrial, where glycine and succinyl CoA combine, catalyzed by the pyridoxal phosphate-dependent enzyme, amino levulinate synthase (Fig. 20.10). 

ALAS (EC 2.3.1.37) uses PLP as a cofactor and catalyzes the one step condensation of glycine and succinyl-CoA to give rise to ALA, carbon dioxide, and free coenzyme A (Figure 3). ALAS belongs to the ct-oxoamine synthase subfamily of PLP-dependent enzymes that typically catalyze the condensation of a carboxylic acid coenzyme A thioester and an amino acid with the concomitant decarboxylation of the latter. Since the first description of ALAS activities in 1958 by Neuberger and coworkers and by Shemin and coworkers, ALAS... 

Depending upon the relative rates of the reactions participating in the interconversion of various species in the ternary complex, one may expect to see spectropho-tometrically the presence of the quinonoid intermediate of type 6 (Fig. 42) in a number of pyridoxal-P-dependent enzymic reactions such an intermediate would be expected to possess a bathochromically shifted long wavelength absorption maximum. This has indeed been clearly viewed for the ternary complex of serine hydroxymethyltransferase with glycine as shown in Fig. 46, the absorption at 495 nm being attributed to the quinonoid intermediate [94]. 

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