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Gene Review

Acox1  -  acyl-Coenzyme A oxidase 1, palmitoyl

Mus musculus

Synonyms: AI042784, AOX, Acox, Acyl-CoA oxidase, D130055E20Rik, ...
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Disease relevance of Acox1


Psychiatry related information on Acox1

  • In mice subjected to 3-day periods of food deprivation an increase in plasma free fatty acids occurred together with a rise in the cardiac content of fatty acyl CoA-oxidase (+ 15.2%) and catalase (+ 136.2%) activities [6].

High impact information on Acox1


Chemical compound and disease context of Acox1


Biological context of Acox1

  • These results suggest that the biological ligands for PPARalpha vis a vis substrates for AOX either are not functional in fetal liver or do not cross the placental barrier during the fetal development and that postnatally they are likely derived from milk and diet [17].
  • Wy-14,643 up-regulated mRNA for liver fatty acid binding protein and peroxisomal beta-oxidation enzymes (acyl-CoA oxidase, bifunctional enzyme, and ketothiolase), thereby reducing hepatic triglycerides and preventing steatosis [18].
  • However, cell death-inducing DNA-fragmentation factor-alpha mRNA, which is increased in the livers of wild-type mice treated with peroxisome proliferators, was not enhanced in AOX-/- mice with spontaneous peroxisome proliferation [19].
  • Our data show that acyl-CoA oxidase is an evolutionary highly conserved enzyme with a distinct pattern of expression and indicate an important role in lipid metabolism [20].
  • In this respect, use of a higher concentration of Triton X-114 for peroxisome fractionation led to the partitioning of some catalase and fatty acyl-CoA oxidase to the detergent phase, indicating the presence of some detergent-accessible hydrophobic binding sites even on these proteins [21].

Anatomical context of Acox1

  • Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism [2].
  • Blunting of microvesicular steatosis, which is restricted to few liver cells in periportal regions in PPARalpha-/- AOX-/- mice, suggests a role for PPARalpha-induced genes, especially members of CYP4A family, in determining the severity of steatosis in livers with defective peroxisomal beta-oxidation [1].
  • In AOX-/- mice, the hyperactivity of PPARalpha enhances the severity of steatosis by inducing CYP4A family proteins that generate DCAs and since they are not metabolized in the absence of peroxisomal beta-oxidation, they damage mitochondria leading to steatosis [1].
  • Acyl-CoA oxidase mRNA and protein expression were most abundant in liver followed by kidney, brain and adipose tissue [20].
  • The mRNA signals for CAT and AOX were detected in sections of complete fetuses, revealing organ- and cell-specific variations [22].

Associations of Acox1 with chemical compounds

  • We then compared the AOX-/- liver tumor expression profiles with those induced by ciprofibrate, a non-genotoxic peroxisome proliferator, or by the genotoxic carcinogen diethylnitrosamine (DENA) to discern differences in gene expression patterns that may predict or distinguish PPARalpha-mediated liver tumors from genotoxically derived tumors [3].
  • The changes observed in HCC and adjacent liver in AOX-/- mice were identical to those observed in rats and mice exposed to peroxisome proliferators [23].
  • A kinetic treatment of the rates of formation of hydrogen peroxide by PCO, and of degradation of hydrogen peroxide by catalase was used to estimate steady-state hydrogen peroxide concentrations ([H2O2]) during peroxisomal oxidation of palmitoyl CoA [24].
  • Clofibric acid, alone and in combination with the S/OA-diet, upregulated CYP4A1-3 and AOX mRNAs [25].
  • Renal expression of CYP4A10, CYP4A14, and acyl-CoA oxidase was induced by LPS treatment in (+/+) mice, and these effects were absent in the (-/-) mice [26].

Physical interactions of Acox1


Regulatory relationships of Acox1


Other interactions of Acox1

  • Fasting did not change the PPAR isoform levels in AOX(-/-) mouse liver [29].
  • L-PBE-/- mice showed no hepatic steatosis and manifested no spontaneous peroxisome proliferation, unlike that encountered in livers of mice deficient in AOX [30].
  • Evidence also indicates that cells stably overexpressing H(2)O(2)-generating fatty acyl-CoA oxidase or urate oxidase, when exposed to appropriate substrate(s), reveal features of neoplastic conversion including growth in soft agar and formation of tumors in nude mice [31].
  • Absence of spontaneous peroxisome proliferation in enoyl-CoA Hydratase/L-3-hydroxyacyl-CoA dehydrogenase-deficient mouse liver. Further support for the role of fatty acyl CoA oxidase in PPARalpha ligand metabolism [30].
  • In contrast to the peroxisomal beta-oxidation marker acyl-CoA oxidase, whose mRNA level steadily increases during brain development, the VLACS transcript was found at a constant low level from embryo through adulthood, suggesting that additional isoforms may exist in brain [32].

Analytical, diagnostic and therapeutic context of Acox1


  1. Peroxisomal and mitochondrial fatty acid beta-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor alpha and peroxisomal fatty acyl-CoA oxidase. Genotype correlation with fatty liver phenotype. Hashimoto, T., Fujita, T., Usuda, N., Cook, W., Qi, C., Peters, J.M., Gonzalez, F.J., Yeldandi, A.V., Rao, M.S., Reddy, J.K. J. Biol. Chem. (1999) [Pubmed]
  2. Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism. Fan, C.Y., Pan, J., Usuda, N., Yeldandi, A.V., Rao, M.S., Reddy, J.K. J. Biol. Chem. (1998) [Pubmed]
  3. Molecular profiling of hepatocellular carcinomas developing spontaneously in acyl-CoA oxidase deficient mice: comparison with liver tumors induced in wild-type mice by a peroxisome proliferator and a genotoxic carcinogen. Meyer, K., Lee, J.S., Dyck, P.A., Cao, W.Q., Rao, M.S., Thorgeirsson, S.S., Reddy, J.K. Carcinogenesis (2003) [Pubmed]
  4. Down-regulation of acyl-CoA oxidase gene expression and increased NF-kappaB activity in etomoxir-induced cardiac hypertrophy. Cabrero, A., Merlos, M., Laguna, J.C., Carrera, M.V. J. Lipid Res. (2003) [Pubmed]
  5. Dose-response relationships of hepatic acyl-CoA oxidase and catalase activity and liver mitogenesis induced by the peroxisome proliferator ciprofibrate in C57BL/6N and BALB/c mice. Budroe, J.D., Umemura, T., Angeloff, K., Williams, G.M. Toxicol. Appl. Pharmacol. (1992) [Pubmed]
  6. Cardiac peroxisomal enzymes and starvation. Crescimanno, M., Armata, M.G., Rausa, L., Gueli, M.C., Nicotra, C., D'Alessandro, N. Free Radic. Res. Commun. (1989) [Pubmed]
  7. Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Lee, J.S., Chu, I.S., Mikaelyan, A., Calvisi, D.F., Heo, J., Reddy, J.K., Thorgeirsson, S.S. Nat. Genet. (2004) [Pubmed]
  8. Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice. Berthou, L., Duverger, N., Emmanuel, F., Langouët, S., Auwerx, J., Guillouzo, A., Fruchart, J.C., Rubin, E., Denèfle, P., Staels, B., Branellec, D. J. Clin. Invest. (1996) [Pubmed]
  9. FRET microscopy demonstrates molecular association of non-specific lipid transfer protein (nsL-TP) with fatty acid oxidation enzymes in peroxisomes. Wouters, F.S., Bastiaens, P.I., Wirtz, K.W., Jovin, T.M. EMBO J. (1998) [Pubmed]
  10. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5' flanking sequence of the rat acyl CoA oxidase gene. Tugwood, J.D., Issemann, I., Anderson, R.G., Bundell, K.R., McPheat, W.L., Green, S. EMBO J. (1992) [Pubmed]
  11. Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferator-responsive elements of the rat hydratase/dehydrogenase and fatty acyl-CoA oxidase genes but differentially induce expression. Marcus, S.L., Miyata, K.S., Zhang, B., Subramani, S., Rachubinski, R.A., Capone, J.P. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  12. Phytanic acid activates the peroxisome proliferator-activated receptor alpha (PPARalpha) in sterol carrier protein 2-/ sterol carrier protein x-deficient mice. Ellinghaus, P., Wolfrum, C., Assmann, G., Spener, F., Seedorf, U. J. Biol. Chem. (1999) [Pubmed]
  13. Induction of hepatic peroxisome proliferation in mice by lactofen, a diphenyl ether herbicide. Butler, E.G., Tanaka, T., Ichida, T., Maruyama, H., Leber, A.P., Williams, G.M. Toxicol. Appl. Pharmacol. (1988) [Pubmed]
  14. Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans? Cattley, R.C., DeLuca, J., Elcombe, C., Fenner-Crisp, P., Lake, B.G., Marsman, D.S., Pastoor, T.A., Popp, J.A., Robinson, D.E., Schwetz, B., Tugwood, J., Wahli, W. Regulatory toxicology and pharmacology : RTP. (1998) [Pubmed]
  15. Heneicosapentaenoate (21:5n-3): its incorporation into lipids and its effects on arachidonic acid and eicosanoid synthesis. Larsen, L.N., Høvik, K., Bremer, J., Holm, K.H., Myhren, F., Børretzen, B. Lipids (1997) [Pubmed]
  16. Examination of potential mechanisms of carcinogenicity of 1,4-dioxane in rat nasal epithelial cells and hepatocytes. Goldsworthy, T.L., Monticello, T.M., Morgan, K.T., Bermudez, E., Wilson, D.M., Jäckh, R., Butterworth, B.E. Arch. Toxicol. (1991) [Pubmed]
  17. Peroxisome proliferator-activated receptor alpha-responsive genes induced in the newborn but not prenatal liver of peroxisomal fatty acyl-CoA oxidase null mice. Cook, W.S., Jain, S., Jia, Y., Cao, W.Q., Yeldandi, A.V., Reddy, J.K., Rao, M.S. Exp. Cell Res. (2001) [Pubmed]
  18. Central role of PPARalpha-dependent hepatic lipid turnover in dietary steatohepatitis in mice. Ip, E., Farrell, G.C., Robertson, G., Hall, P., Kirsch, R., Leclercq, I. Hepatology (2003) [Pubmed]
  19. Identification of novel peroxisome proliferator-activated receptor alpha (PPARalpha) target genes in mouse liver using cDNA microarray analysis. Cherkaoui-Malki, M., Meyer, K., Cao, W.Q., Latruffe, N., Yeldandi, A.V., Rao, M.S., Bradfield, C.A., Reddy, J.K. Gene Expr. (2001) [Pubmed]
  20. cDNA cloning and analysis of tissue-specific expression of mouse peroxisomal straight-chain acyl-CoA oxidase. Nöhammer, C., El-Shabrawi, Y., Schauer, S., Hiden, M., Berger, J., Forss-Petter, S., Winter, E., Eferl, R., Zechner, R., Hoefler, G. Eur. J. Biochem. (2000) [Pubmed]
  21. Protein organization in mouse liver peroxisomes. Poole, C.B., Crane, D.I. Arch. Biochem. Biophys. (1992) [Pubmed]
  22. Detection of peroxisomal proteins and their mRNAs in serial sections of fetal and newborn mouse organs. Grabenbauer, M., Fahimi, H.D., Baumgart, E. J. Histochem. Cytochem. (2001) [Pubmed]
  23. Expression of peroxisome proliferator-activated receptor alpha, and PPARalpha regulated genes in spontaneously developed hepatocellular carcinomas in fatty acyl-CoA oxidase null mice. Meyer, K., Jia, Y., Cao, W.Q., Kashireddy, P., Rao, M.S. Int. J. Oncol. (2002) [Pubmed]
  24. In vitro steady-state levels of hydrogen peroxide after exposure of male F344 rats and female B6C3F1 mice to hepatic peroxisome proliferators. Tomaszewski, K.E., Agarwal, D.K., Melnick, R.L. Carcinogenesis (1986) [Pubmed]
  25. Pretranslational upregulation of microsomal CYP4A in rat liver by intake of a high-sucrose, lipid-devoid diet containing orotic acid. Su, G.M., Fiala-Beer, E., Weber, J., Jahn, D., Robertson, G.R., Murray, M. Biochem. Pharmacol. (2005) [Pubmed]
  26. Modulation of cytochrome P-450 gene expression in endotoxemic mice is tissue specific and peroxisome proliferator-activated receptor-alpha dependent. Barclay, T.B., Peters, J.M., Sewer, M.B., Ferrari, L., Gonzalez, F.J., Morgan, E.T. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  27. The peroxisome proliferator-activated receptor mediates the induction of CYP4A6, a cytochrome P450 fatty acid omega-hydroxylase, by clofibric acid. Muerhoff, A.S., Griffin, K.J., Johnson, E.F. J. Biol. Chem. (1992) [Pubmed]
  28. Expression of the hydrogen peroxide-generating enzyme fatty acyl CoA oxidase activates NF-kappaB. Li, Y., Tharappel, J.C., Cooper, S., Glenn, M., Glauert, H.P., Spear, B.T. DNA Cell Biol. (2000) [Pubmed]
  29. Defect in peroxisome proliferator-activated receptor alpha-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. Hashimoto, T., Cook, W.S., Qi, C., Yeldandi, A.V., Reddy, J.K., Rao, M.S. J. Biol. Chem. (2000) [Pubmed]
  30. Absence of spontaneous peroxisome proliferation in enoyl-CoA Hydratase/L-3-hydroxyacyl-CoA dehydrogenase-deficient mouse liver. Further support for the role of fatty acyl CoA oxidase in PPARalpha ligand metabolism. Qi, C., Zhu, Y., Pan, J., Usuda, N., Maeda, N., Yeldandi, A.V., Rao, M.S., Hashimoto, T., Reddy, J.K. J. Biol. Chem. (1999) [Pubmed]
  31. Hydrogen peroxide generation in peroxisome proliferator-induced oncogenesis. Yeldandi, A.V., Rao, M.S., Reddy, J.K. Mutat. Res. (2000) [Pubmed]
  32. cDNA cloning and mRNA distribution of a mouse very long-chain acyl-CoA synthetase. Berger, J., Truppe, C., Neumann, H., Forss-Petter, S. FEBS Lett. (1998) [Pubmed]
  33. Fenofibrate, a ligand for PPARalpha, inhibits aromatase cytochrome P450 expression in the ovary of mouse. Toda, K., Okada, T., Miyaura, C., Saibara, T. J. Lipid Res. (2003) [Pubmed]
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