Oxidase a-hydroxy acid

D-Amino acid oxidase occurs in peroxisomes containing other enzymes that produce H2O2 (e.g., L-a-hydroxy acid oxidase, citrate dehydrogenase, and L-amino acid oxidase) and catalase and peroxidase, which destroy H2O2. In leukocytes, killing of bacteria involves hydrolases of lysosomes and production of H2O2 by NADPH oxidase (Chapter 15). Conversion of D-amino acids to the corresponding a-keto acids removes the asymmetry at the a-carbon atom. The keto acids may be aminated to L-amino acids. By this conversion from D- to L-amino acids, the body utilizes D-amino acids derived from the diet ... 

The FAD-requiring enzymes in mammalian systems include the D- and L-amino acid oxidases, mono- and diamine oxidases, glucose oxidase, succinate dehydrogenase, a-glycerophosphate dehydrogenase, and glutathione reductase. FMN is a cofactor for renal L-amino acid oxidase, NADH reductase, and a-hydroxy acid oxidase. In succinate dehydrogenase, FAD is linked to a histidyl residue in liver mitochondrial monoamine oxidase, to a cysteinyl residue. In other cases, the attachment is nonco-valent but the dissociation constant is very low. 

Glycolate oxidase L-a-Hydroxy acid oxidase D-Amino acid oxidase Urate oxidase... 

Allen JM and Beard ME (1965) a-Hydroxy acid oxidase localization in renal microbodies. Science 149 1507-1509... 

In a related approach, Adam ef al. used glycolate oxidase with D-lactate dehydrogenase for the deracemization of a wide range of racemic a-hydroxy acids (20) (Figure 5.13) [23]. 

Enzymes with an intermittent role may be much more important than we thought in 1963. This was perhaps first clearly emphasized by Deis-seroth and Bounce in their catalase review of 1970 (25). These authors also pointed out the likelihood that the specific location of most eukaryotic catalase in the peroxisomes represents a functional response to the need to decompose hydrogen peroxide generated by the aerobic oxidases present in these same organelles, including hydroxy-acid oxidases and D-amino-acid oxidases. 

This FMN-dependent enzyme [EC 1.1.3.15], also known as (5)-2-hydroxy-acid oxidase, catalyzes the reaction of a (5)-2-hydroxy acid with dioxygen to produce a 2-oxo acid and hydrogen peroxide. The enzyme exists as two major isoenzymes. The A form of the protein preferentially oxidizes short-chain aliphatic hydroxy acids. The B form preferentially oxidizes long-chain and aromatic hydroxy acids. The rat isoenzyme B form also acts as an L-amino-acid oxidase. 

Various oxidations. An a-oxidase from peas mediates the enantioselective oxidation of hydroxylation of carboxylic acids [to give products of (/f)-configuration]. On the other hand, a-hydroxy acids undergo oxidative decarboxylation, and the process renders methylmandelate as a benzoyl anion equivalent. ... 

Fi>2 is a member of a family of homologous flavoproteins that catalyze the oxidation of a-hydroxy acids. It is located in the intermembrane space of yeast mitochondria and provides pyruvate for the Krebs cycle as well as participates in a short electron-transfer chain involving cytochrome c and cytochrome oxidase, making it an important respiratory enzyme. Unlike many other flavoproteins that oxidize a-hydroxy acids, F 2 has very poor reactivity toward oxygen. Fi>2 is a homotetramer with each monomer containing both an FMN and a heme The catalytic cycle has five redox steps (Scheme 7). In the first step, lactate is oxidized to... 

L-lactate oxidase (LOX) catalyzes the oxidation of L-lactate to pyruvate with the concomitant reduction of the enzyme-hound FMN. The reduced enzyme is oxidized hy molecular oxygen resulting in oxidized enzyme and H207- LOX has substantial sequence homology to other a-hydroxy acid oxidizing flavoproteins, containing all the residues thought to he important for catalysis in this class of enzymes/... 

A contrasting mode of flavoprotein reactivity with an acetylenic inactivator occurs in the reaction of 2-hydroxy-3-butynoate (13, Fig. 15) with a number of a-hydroxy acid oxidizing enzymes. This process is exemplified by the inactivation of L-lactate oxidase from Mycobacterium smegmatis, an enzyme which catalyzes the oxidative decarboxylation of lactate to yield acetate, carbon dioxide, and water (Walsh, 1979, p. 408). Incubation of 13 with lactate oxidase leads to inactivation of the enzyme with a partition ratio that varies from 110 in the... 

It has been shown that these organelles contain peroxidase, catalase, uricase, and a number of other oxidases, such as D amino oxidase, L-hydroxy acid oxidase, and even isocitrate dehydrogenase [264]. Because of their content in peroxidase, microbodies have been renamed peroxisomes. Nothing is known of their role in cellular physiology. Usually on the basis of circumstantial evidence they have been suspected to play a role in purine (because of the presence of xanthine oxidase and allantoinase in the kidney and liver of chicken microbodies), cholesterol, lipid, and steroid metabolisms, gluconeogenesis, photosynthesis, and respiration. 

The propionate oxidase can be obtained as a saline extract from acetone-dried, washed liver cyclophorase preparation. This enzyme is very labile and loses its activity within several hours after its preparation even at 5 C. or in the frozen state. The material called a-hydroxy acid racemase is found in the first supernatant fluid of cyclophorase preparations of either liver or kidney. The active substance appears to be a protein fairly stable to elevated temperatures, repeated freezing and thawing, and precipitation by acetone and alcohol. 

An estimation of the amount of amino acid production and the production methods are shown ia Table 11. About 340,000 t/yr of L-glutamic acid, principally as its monosodium salt, are manufactured ia the world, about 85% ia the Asian area. The demand for DL-methionine and L-lysiae as feed supplements varies considerably depending on such factors as the soybean harvest ia the United States and the anchovy catch ia Pern. Because of the actions of D-amiao acid oxidase and i.-amino acid transamiaase ia the animal body (156), the D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is iaexpensively produced by chemical synthesis is primarily used as a feed supplement. In the United States the methionine hydroxy analogue is partially used ia place of methionine. The consumption of L-lysiae has iacreased ia recent years. The world consumption tripled from 35,000 t ia 1982 to 100,000 t ia 1987 (214). Current world consumption of L-tryptophan and i.-threonine are several tens to hundreds of tons. The demand for L-phenylalanine as the raw material for the synthesis of aspartame has been increasing markedly. 

W Adam, W Boland, J Hartmann-Schreier, H-U Humpf, M Lazarus, A Saffert, CR Saha-Moller, P Schreier. a Hydroxylation of carboxylic acids with molecular oxygen catalyzed by the a oxidase of peas (Pisum sativum) a novel biocatalytic synthesis of enantiomerically pure (R)-2-hydroxy acids. J Am Chem Soc 120 11044— 11048, 1998. 

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