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ACYL-CoA OXIDASE 2, BRANCHED-CHAIN; ACOX2

Alternative titles; symbols
ACYL-CoA OXIDASE, BRANCHED-CHAIN, PEROXISOMAL
BRANCHED-CHAIN ACYL-CoA OXIDASE; BRCACOX; BCOX

Gene map locus 3p14.3

TEXT

Baumgart et al. (1996) stated that greater than half of the enzymes present in mammalian peroxisomes are associated intimately with lipid metabolism. Thus, peroxisomes are involved in the beta-oxidation of very long straight-chain fatty acids and branched-chain fatty acids, dicarboxylic fatty acids, and eicosanoids. They are also responsible for the beta-oxidation of the side chain of the bile acid intermediates di- and trihydroxycoprostanic acids, resulting in the formation of the primary bile acids (chenodeoxycholic and cholic acid, respectively). Most likely, the different substrates are degraded by distinct beta-oxidation pathways. Peroxisomes in human liver contain 2 distinct acyl-CoA oxidases with different substrate specificities: palmitoyl-CoA oxidase (609751), oxidizing very long straight-chain fatty acids and eicosanoids, and a branched-chain acyl-CoA oxidase, involved in the degradation of long branched fatty acids and bile acid intermediates. The accumulation of branched fatty acids and bile acid intermediates leads to severe mental retardation and death of affected children. Deficiency of acyl-CoA oxidase (palmitoyl-CoA oxidase) results in pseudoneonatal adrenoleukodystrophy (264470).

Baumgart et al. (1996) reported the molecular characterization of branched-chain acyl-CoA oxidase. Its composite cDNA sequence, derived from overlapping clones isolated by immunoscreening and hybridization of human liver cDNA expression libraries, consists of 2,225 bp and contains an open reading frame of 2,046 bp, encoding a protein of 681 amino acids with a calculated molecular mass of 76,739 Da. The C-terminal tripeptide of the protein was found to be SKL (ser-lys-leu), a known peroxisome targeting signal. Sequence comparison with the other acyl-CoA oxidases and evolutionary analysis demonstrated that, despite its broader substrate specificity, this branched-chain acyl-CoA oxidase is the human homolog of rat trihydroxycoprostanoyl-CoA oxidase and that separate gene duplication events led to the occurrence in mammals of acyl-CoA oxidases with different substrate specificities. Northern blot analysis demonstrated that, in contrast to the rat gene, the human gene is transcribed also in extra hepatic tissues, such as heart, kidney, skeletal muscle, and pancreas. The highest levels of the 2.6-kb mRNA were found in heart, followed by liver. The enzyme was absent from livers of Zellweger patients, as shown by immunoblot analysis and immunocytochemistry. Palmitoyl-CoA oxidase was also absent, whereas even in autolytic samples of human control livers both acyl-CoA oxidases were present. Baumgart et al. (1996) noted that the deficiency of these enzymes is part of the generalized deficiency in peroxisomal beta-oxidation enzymes in Zellweger syndrome (214100).

Baumgart et al. (1996) isolated the rat trihydroxycoprostanoyl-CoA oxidase cDNA sequenced by screening rat liver cDNA expression libraries. The gene contains a 2,046-bp open reading frame encoding a protein of 681 amino acids with a calculated molecular mass of 76,711 Da. This sequence shares 45% amino acid identity with rat palmitoyl-CoA oxidase and 22% with rat pristanoyl-CoA oxidase. The C terminus (his-lys-met) of trihydroxycoprostanoyl-CoA oxidase does not appear to interact with the C-terminal peroxisomal targeting signal 1 (PTS1) import receptor (PEX5; 600414), although the tripeptide fits the rule of conserved variants for targeting of proteins to glycosomes of Trypanosomatidea. Northern analysis of multiple rat tissues revealed a 2.6-kb transcript only in liver and kidney.

Baumgart et al. (1996) assigned the single-copy gene to 3p14.3 by fluorescence in situ hybridization (FISH). Moghrabi et al. (1997) used PCR and rodent/human hybrids to map the gene encoding peroxisomal branched-chain acyl-CoA oxidase to human chromosome 3p21.1-p14.2.

REFERENCES

1. Baumgart, E.; Vanhooren, J. C. T.; Fransen, M.; Marynen, P.; Puype, M.; Vandekerckhove, J.; Leunissen, J. A. M.; Fahimi, H. D.; Mannaerts, G. P.; Van Veldhoven, P. P. :: 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. Proc. Nat. Acad. Sci. 93: 13748-13753, 1996.
PubMed ID : 8943006
2. Baumgart, E.; Vanhooren, J. C. T.; Fransen, M.; Van Leuven, F.; Fahimi, H. D.; Van Veldhoven, P. P.; Mannaerts, G. P. :: Molecular cloning and further characterization of rat peroxisomal trihydroxycoprostanoyl-CoA oxidase. Biochem. J. 320: 115-121, 1996.
PubMed ID : 8947475
3. Moghrabi, N. N.; Naylor, S. L.; Van Veldhoven, P. P.; Baumgart, E.; Dawson, D. B.; Bennett, M. J. :: Assignment of the human peroxisomal branched-chain acyl-CoA oxidase gene to chromosome 3p21.1-p14.2 by rodent/human somatic cell hybridization. Biochem. Biophys. Res. Commun. 231: 767-769, 1997.
PubMed ID : 9070889

CONTRIBUTORS

Jennifer P. Macke - updated : 5/1/1998
Ethylin Wang Jabs - updated : 11/11/1997

CREATION DATE

Victor A. McKusick : 1/22/1997

EDIT HISTORY