Disease relevance of ACOX3

• Furthermore, our data suggest that pristanoyl-CoA oxidase (ACOX3), which is expressed at extremely low level in other human organs studied including the liver, might contribute significantly to peroxisomal branched chain fatty acid beta-oxidation in human prostate tissue and some prostate cancer cell lines [1].

High impact information on ACOX3

• Molecular characterization of the human peroxisomal branched-chain acyl-CoA oxidase: cDNA cloning, chromosomal assignment, tissue distribution, and evidence for the absence of the protein in Zellweger syndrome [2].
• Peroxisomes in human liver contain two distinct acyl-CoA oxidases with different substrate specificities: (i) palmitoyl-CoA oxidase, oxidizing very long straight-chain fatty acids and eicosanoids, and (ii) a branched-chain acyl-CoA oxidase (hBRCACox), involved in the degradation of long branched fatty acids and bile acid intermediates [2].
• Northern blot analysis demonstrated that--in contrast to the rTHCCox gene--the hBRCACox gene is transcribed also in extrahepatic tissues such as heart, kidney, skeletal muscle, and pancreas [2].
• The composite cDNA sequence of hBRCACox, derived from overlapping clones isolated via immunoscreening and hybridization of human liver cDNA expression libraries, consisted of 2225 bases and contained an open reading frame of 2046 bases, encoding a protein of 681 amino acids with a calculated molecular mass of 76,739 Da [2].
• The obtained sequence showed 73.6% similarity with a proposed rat THCA-CoA oxidase and 81% similarity with a recently reported human branched chain acyl-CoA oxidase, indicating that these three proteins represent the same enzyme [3].

Biological context of ACOX3

• By means of fluorescence in situ hybridization the gene for human pristanoyl-CoA oxidase was mapped at chromosome position 4p15 [4].
• 3. We conclude that a gene for pristanoyl-CoA oxidase is present in the human genome [4].
• In the human, these compounds are oxidized by a single enzyme, branched-chain acyl-CoA oxidase, which according to its amino acid sequence is the human homologue of rat trihydroxycoprostanoyl-CoA oxidase [4].
• Identification of pristanoyl-CoA oxidase and phytanic acid decarboxylation in peroxisomes and mitochondria from human liver: implications for Zellweger syndrome [5].

Anatomical context of ACOX3

• PCR and rodent/human somatic cell hybrids were used to localize the human peroxisomal branched-chain acyl-CoA oxidase gene [6].
• We postulated that these results might be due to deficiency of the peroxisomal branched-chain acyl-CoA oxidase, but when oxidation of branched-chain fatty acids was studied in cultured skin fibroblasts it was found to be normal [7].

Associations of ACOX3 with chemical compounds

• The CoA esters of 2-methyl-branched chain fatty acids and of the bile acid intermediates di- and trihydroxycoprostanic acids are oxidized by one single peroxisomal branched chain acyl-CoA oxidase in human liver and kidney [8].
• These data, combined with the fact that the branched chain acyl-CoA oxidase, catalyzing the first oxidation step of pristanic acid and bile acid intermediates in man, appeared normal, suggested a peroxisomal beta-oxidation defect in the patient at the level of 2-methylacyl-CoA racemase [9].

Other interactions of ACOX3

• 2-Methyl-branched acyl-CoAs are degraded via pristanoyl-CoA oxidase, multifunctional protein-2 (MFP-2) (which displays 2-enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase activities) and sterol carrier protein-X (SCPX; displaying 2-methyl-3-oxoacyl-CoA thiolase activity) [10].

Analytical, diagnostic and therapeutic context of ACOX3

• As revealed by Northern and Western blotting there was marked elevation of the mRNA (190%) and protein (180%) of the peroxisomal branched-chain acyl-CoA oxidase [11].

References