HAO1: Human hydroxyacid oxidase 1
PDB Code: 2NZL
The metabolism of fatty acids proceeds through alpha- and beta-oxidation pathways, depending on the substrate. Whereas beta-oxidation occurs on straight alkyl-chains mostly in mitochondria, the metabolism of 3-methyl branched chain fatty acids proceeds through an initial alpha oxidation step, found in peroxisomes, followed by several rounds of beta oxidation. Although not all details of the alpha oxidation pathway are established yet, oxidation of 2-hydroxyacid intermediates generated in the alpha oxidation pathway to hydrogenperoxide and keto acids that are decarboxylated, is postulated. The recent discovery of 3 human 2-hydroxyacid oxidases (HAOX1-3) and their functional characterization as 2-hydroxyacid oxidases suggest an involvement of these peroxisomal enzymes in alpha oxidation pathways.
The HAOX enzymes belong to the FMN-dependent alpha-hydroxy acid dehydrogenase family, and are related to plant glycolate oxidases. The expression of HAOX1 in liver and kidney as well as the ability to oxidize glyoxylate to oxalate suggest an involvement of this enzyme in primary hyperoxaluria type 1.
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