Publications

• Purification and characterization of glycolic acid oxidase from pig liver.

  Schuman M., Massey V.

  Biochim Biophys Acta 227:500-520(1971) [PubMed] [EuropePMC]

• Identification and characterization of HAOX1, HAOX2, and HAOX3, three human peroxisomal 2-hydroxy acid oxidases.

  Jones J.M., Morrell J.C., Gould S.J.

  Computer-based approaches identified three distinct human 2-hydroxy acid oxidase genes, HAOX1, HAOX2, and HAOX3, that encode proteins with significant sequence similarity to plant glycolate oxidase, a prototypical 2-hydroxy acid oxidase. The products of these genes are targeted to peroxisomes and ... >> More

  Computer-based approaches identified three distinct human 2-hydroxy acid oxidase genes, HAOX1, HAOX2, and HAOX3, that encode proteins with significant sequence similarity to plant glycolate oxidase, a prototypical 2-hydroxy acid oxidase. The products of these genes are targeted to peroxisomes and have 2-hydroxy acid oxidase activities. Each gene displays a distinct tissue-specific pattern of expression, and each enzyme exhibits distinct substrate preferences. HAOX1 is expressed primarily in liver and pancreas and is most active on the two-carbon substrate, glycolate, but is also active on 2-hydroxy fatty acids. HAOX2 is expressed predominantly in liver and kidney and displays highest activity toward 2-hydroxypalmitate. HAOX3 expression was detected only in pancreas, and this enzyme displayed a preference for the medium chain substrate 2-hydroxyoctanoate. These results indicate that all three human 2-hydroxy acid oxidases are involved in the oxidation of 2-hydroxy fatty acids and may also contribute to the general pathway of fatty acid alpha-oxidation. Primary hyperoxaluria type 1 (PH1) is caused by defects in peroxisomal alanine-glyoxylate aminotransferase, the enzyme that normally eliminates intraperoxisomal glyoxylate. The presence of HAOX1 in liver and kidney peroxisomes and the ability of HAOX1 to oxidize glyoxylate to oxalate implicate HAOX1 as a mediator of PH1 pathophysiology. << Less

  J. Biol. Chem. 275:12590-12597(2000) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Oxalate accumulation and regulation is independent of glycolate oxidase in rice leaves.

  Xu H.-W., Ji X.-M., He Z.-H., Shi W.-P., Zhu G.-H., Niu J.-K., Li B.-S., Peng X.-X.

  Cellular oxalate, widely distributed in many plants, is implicated to play important roles in various functions and is also known to affect food qualities adversely in fruits and vegetables. How oxalate is regulated in plants is currently not well understood. Glycolate oxidase (GLO) has long been ... >> More

  Cellular oxalate, widely distributed in many plants, is implicated to play important roles in various functions and is also known to affect food qualities adversely in fruits and vegetables. How oxalate is regulated in plants is currently not well understood. Glycolate oxidase (GLO) has long been considered as an important player in oxalate accumulation in plants. To gain further insight into the biochemical and molecular mechanisms, the possible roles of GLO in the process were studied. Drastically different levels of oxalate could be achieved by treating rice with various nitrogen forms (nitrate versus ammonium). While nitrate stimulated oxalate accumulation, ammonium reduced its level. Such treatments resulted in similar pattern changes for some other related organic acids, such as glycolate, oxaloacetate, and malate. By feeding plants with exogenous glycolate it was possible almost completely to restore the ammonium-decreased oxalate level. Under the two treatments few differences were observed for GLO mRNA levels, protein levels, and in vitro activities. Both K(m) for glycolate/glyoxylate and K(i) for oxalate remained almost the same for GLO purified from either nitrate- or ammonium-fed leaves. A further in vivo study, with transgenic plants carrying an estradiol-inducible GLO antisense gene, showed that, while the estradiol-induced antisense expression remarkably reduced both GLO protein levels and activities, oxalate levels were not significantly altered in the estradiol-treated transgenic plants. Taken together, it is suggested that oxalate accumulation and regulation is independent of GLO in rice leaves. << Less

  J. Exp. Bot. 57:1899-1908(2006) [PubMed] [EuropePMC]

• Active site and loop 4 movements within human glycolate oxidase: implications for substrate specificity and drug design.

  Murray M.S., Holmes R.P., Lowther W.T.

  Human glycolate oxidase (GO) catalyzes the FMN-dependent oxidation of glycolate to glyoxylate and glyoxylate to oxalate, a key metabolite in kidney stone formation. We report herein the structures of recombinant GO complexed with sulfate, glyoxylate, and an inhibitor, 4-carboxy-5-dodecylsulfanyl-1 ... >> More

  Human glycolate oxidase (GO) catalyzes the FMN-dependent oxidation of glycolate to glyoxylate and glyoxylate to oxalate, a key metabolite in kidney stone formation. We report herein the structures of recombinant GO complexed with sulfate, glyoxylate, and an inhibitor, 4-carboxy-5-dodecylsulfanyl-1,2,3-triazole (CDST), determined by X-ray crystallography. In contrast to most alpha-hydroxy acid oxidases including spinach glycolate oxidase, a loop region, known as loop 4, is completely visible when the GO active site contains a small ligand. The lack of electron density for this loop in the GO-CDST complex, which mimics a large substrate, suggests that a disordered to ordered transition may occur with the binding of substrates. The conformational flexibility of Trp110 appears to be responsible for enabling GO to react with alpha-hydroxy acids of various chain lengths. Moreover, the movement of Trp110 disrupts a hydrogen-bonding network between Trp110, Leu191, Tyr134, and Tyr208. This loss of interactions is the first indication that active site movements are directly linked to changes in the conformation of loop 4. The kinetic parameters for the oxidation of glycolate, glyoxylate, and 2-hydroxy octanoate indicate that the oxidation of glycolate to glyoxylate is the primary reaction catalyzed by GO, while the oxidation of glyoxylate to oxalate is most likely not relevant under normal conditions. However, drugs that exploit the unique structural features of GO may ultimately prove to be useful for decreasing glycolate and glyoxylate levels in primary hyperoxaluria type 1 patients who have the inability to convert peroxisomal glyoxylate to glycine. << Less

  Biochemistry 47:2439-2449(2008) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.