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Gene Review

ACOX1  -  acyl-CoA oxidase 1, palmitoyl

Homo sapiens

Synonyms: ACOX, AOX, PALMCOX, Palmitoyl-CoA oxidase, Peroxisomal acyl-coenzyme A oxidase 1, ...
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Disease relevance of ACOX1

  • We have constructed a full-length cDNA encoding a 660-amino acid residue human ACOX and produced a catalytically active human ACOX protein at high levels in Spodoptera frugiperda (Sf9) insect cells using the baculovirus vector [1].
  • Analysis of peroxisomal marker enzyme activities confirmed that peroxisome proliferators induced acyl-CoA oxidase (ACOX) and to a lesser extent catalase in rat hepatocytes, but not in human hepatoma HepG2 cells [2].
  • These include PTOX orthologues present in four different cyanobacteria as well as an AOX orthologue in an alpha-proteobacterium [3].
  • We propose that during anoxia, plant cells can prepare for reoxygenation injury by up-regulating their antioxidant capacity, and that AOX is involved in this process [4].
  • These include the acyl-CoA oxidase (AOX), the liver carnitine palmitoyltransferase 1 (L-CPT 1) and the liver fatty acid binding protein (L-FABP) [5].

Psychiatry related information on ACOX1


High impact information on ACOX1

  • Evidence to support this idea comes from the metabolic role of alternative respiration under stress, the link between AOX activity and differential growth, and the single nucleotide polymorphism recently observed in AOX genes [7].
  • In this Opinion article, we propose a role for the alternative oxidase (AOX) gene as a marker for genetic variation in cell reprogramming and yield stability [7].
  • 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 [8].
  • The discovery of carcinogenic peroxisome proliferators, which markedly increase the levels of this H2O2-producing ACOX in rat and mouse liver, generated interest in peroxisomal beta-oxidation system genes [9].
  • This ACOX gene has been mapped to chromosome 17q25 by in situ hybridization, using a biotinlabeled probe [9].

Chemical compound and disease context of ACOX1

  • Effective AOX and acute toxicity removal was also obtained after heterogeneous photocatalytic treatment (TiO(2)/UV-A and TiO(2)/UV-A/H(2)O(2)) [10].
  • The Fenton-based treatment experiments and particularly the dark Fenton reaction resulted in relatively poor degradation, dearomatization, AOX and acute toxicity removals [10].

Biological context of ACOX1


Anatomical context of ACOX1

  • In the cDNA-expression experiment, significant amount of AOX was accumulated in human skin fibroblast and the expressed AOX was catalytically active, while only a limited amount was found in Zellweger syndrome patient's fibroblast not having normal peroxisomes [13].
  • During the first 3-4 months of age, the livers of ACOX -/- mice reveal severe microvesicular fatty metamorphosis of hepatocytes [14].
  • The amount of ACOX increased and reached to the maximum activity by day 5 of germination but decreased about 4-fold on the following days during the subsequent microbody transition from glyoxysomes to leaf peroxisomes [15].
  • The expressed AOX seems to be confined to mitochondria [16].
  • An extensive phylogeny of newly found prokaryotic and eukaryotic AOX and PTOX proteins supports the idea that AOX and PTOX represent two distinct groups of proteins that diverged prior to the endosymbiotic events that gave rise to the eukaryotic organelles [3].

Associations of ACOX1 with chemical compounds

  • The palmitoyl-CoA oxidase (ACOX) oxidizes the CoA esters of straight chain fatty acids and prostaglandins and donates electrons directly to molecular oxygen, thereby producing H2O2 [1].
  • Carboxyl-terminal sequences Ser-Lys-Leu (SKL) and Leu-Gln-Ser-Lys-Leu (LQSKL) of acyl-CoA oxidase (AOX) directed to peroxisomes the fused proteins with import-incompetent forms of AOX and catalase that had been truncated, implying that the SKL tripeptide functions as a targeting signal [17].
  • In general, as the concentration of these hypolipidemic agents increased from 0 to 1000 microM, the specific activities of peroxisomal palmitoyl-CoA oxidase and catalase increased, and mitochondrial carnitine palmitoyl-CoA transferase and succinate-INT-reductase decreased [18].
  • Activities of two peroxisomal enzymes, palmitoyl-CoA oxidase and catalase, and two mitochondrial enzymes, carnitine palmitoyl-CoA transferase and succinate-INT-reductase, were measured in CLO- and DHEA-treated cells [18].
  • In potato (Solanum tuberosum L.) suspension cells, the expression of the gene encoding alternative oxidase (AOX) and H2O2 accumulation were induced by treatment with beta-glucan elicitor [12].

Regulatory relationships of ACOX1

  • The inhibition of catalase activity enhanced both AOX mRNA expression and the production of H2O2, whereas the ascorbate peroxidase inhibitor did not have any effect on these responses [12].

Other interactions of ACOX1


Analytical, diagnostic and therapeutic context of ACOX1


  1. Overexpression and characterization of the human peroxisomal acyl-CoA oxidase in insect cells. Chu, R., Varanasi, U., Chu, S., Lin, Y., Usuda, N., Rao, M.S., Reddy, J.K. J. Biol. Chem. (1995) [Pubmed]
  2. Characterization of the species-specificity of peroxisome proliferators in rat and human hepatocytes. Ammerschlaeger, M., Beigel, J., Klein, K.U., Mueller, S.O. Toxicol. Sci. (2004) [Pubmed]
  3. Prokaryotic orthologues of mitochondrial alternative oxidase and plastid terminal oxidase. McDonald, A.E., Amirsadeghi, S., Vanlerberghe, G.C. Plant Mol. Biol. (2003) [Pubmed]
  4. Anoxia pretreatment protects soybean cells against H(2)O(2)-induced cell death: possible involvement of peroxidases and of alternative oxidase. Amora, Y., Chevionb, M., Levinea, A. FEBS Lett. (2000) [Pubmed]
  5. Is there a single mechanism for fatty acid regulation of gene transcription? Duplus, E., Forest, C. Biochem. Pharmacol. (2002) [Pubmed]
  6. AOX formation and elimination in the oxidative treatment of synthetic wastewaters in a UV-free surface reactor. Baycan, N., Sengul, F., Thomanetz, E. Environmental science and pollution research international. (2005) [Pubmed]
  7. AOX--a functional marker for efficient cell reprogramming under stress? Arnholdt-Schmitt, B., Costa, J.H., de Melo, D.F. Trends Plant Sci. (2006) [Pubmed]
  8. 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. Baumgart, E., Vanhooren, J.C., Fransen, M., Marynen, P., Puype, M., Vandekerckhove, J., Leunissen, J.A., Fahimi, H.D., Mannaerts, G.P., van Veldhoven, P.P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter analysis, and chromosomal localization. Varanasi, U., Chu, R., Chu, S., Espinosa, R., LeBeau, M.M., Reddy, J.K. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  10. Degradation of a commercial textile biocide with advanced oxidation processes and ozone. Arslan-Alaton, I. J. Environ. Manage. (2007) [Pubmed]
  11. Differential regulation of the cynomolgus, human, and rat acyl-CoA oxidase promoters by PPARalpha. Kane, C.D., Francone, O.L., Stevens, K.A. Gene (2006) [Pubmed]
  12. Catalase and alternative oxidase cooperatively regulate programmed cell death induced by beta-glucan elicitor in potato suspension cultures. Mizuno, M., Tada, Y., Uchii, K., Kawakami, S., Mayama, S. Planta (2005) [Pubmed]
  13. Molecular cloning and functional expression of a human peroxisomal acyl-coenzyme A oxidase. Aoyama, T., Tsushima, K., Souri, M., Kamijo, T., Suzuki, Y., Shimozawa, N., Orii, T., Hashimoto, T. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  14. Hepatocellular and hepatic peroxisomal alterations in mice with a disrupted peroxisomal fatty acyl-coenzyme A oxidase gene. Fan, C.Y., Pan, J., Chu, R., Lee, D., Kluckman, K.D., Usuda, N., Singh, I., Yeldandi, A.V., Rao, M.S., Maeda, N., Reddy, J.K. J. Biol. Chem. (1996) [Pubmed]
  15. Molecular characterization of a glyoxysomal long chain acyl-CoA oxidase that is synthesized as a precursor of higher molecular mass in pumpkin. Hayashi, H., De Bellis, L., Yamaguchi, K., Kato, A., Hayashi, M., Nishimura, M. J. Biol. Chem. (1998) [Pubmed]
  16. Allotopic expression of a mitochondrial alternative oxidase confers cyanide resistance to human cell respiration. Hakkaart, G.A., Dassa, E.P., Jacobs, H.T., Rustin, P. EMBO Rep. (2006) [Pubmed]
  17. Carboxyl-terminal consensus Ser-Lys-Leu-related tripeptide of peroxisomal proteins functions in vitro as a minimal peroxisome-targeting signal. Miura, S., Kasuya-Arai, I., Mori, H., Miyazawa, S., Osumi, T., Hashimoto, T., Fujiki, Y. J. Biol. Chem. (1992) [Pubmed]
  18. Inverse relationship between peroxisomal and mitochondrial beta-oxidation in HepG2 cells treated with dehydroepiandrosterone and clofibric acid. Chance, D.S., Wu, S.M., McIntosh, M.K. Proc. Soc. Exp. Biol. Med. (1995) [Pubmed]
  19. Multiple peroxisomal enzymatic deficiency disorders. A comparative biochemical and morphologic study of Zellweger cerebrohepatorenal syndrome and neonatal adrenoleukodystrophy. Vamecq, J., Draye, J.P., Van Hoof, F., Misson, J.P., Evrard, P., Verellen, G., Eyssen, H.J., Van Eldere, J., Schutgens, R.B., Wanders, R.J. Am. J. Pathol. (1986) [Pubmed]
  20. Evaluation of oxidative processes in human pigment epithelial cells associated with retinal outer segment phagocytosis. Miceli, M.V., Liles, M.R., Newsome, D.A. Exp. Cell Res. (1994) [Pubmed]
  21. Effects of di-isononyl phthalate (DINP) on peroxisomal markers in the marmoset-DINP is not a peroxisome proliferator. Hall, M., Matthews, A., Webley, L., Harling, R. The Journal of toxicological sciences. (1999) [Pubmed]
  22. Peroxisomal straight-chain Acyl-CoA oxidase and D-bifunctional protein are essential for the retroconversion step in docosahexaenoic acid synthesis. Su, H.M., Moser, A.B., Moser, H.W., Watkins, P.A. J. Biol. Chem. (2001) [Pubmed]
  23. Separate peroxisomal oxidases for fatty acyl-CoAs and trihydroxycoprostanoyl-CoA in human liver. Casteels, M., Schepers, L., Van Veldhoven, P.P., Eyssen, H.J., Mannaerts, G.P. J. Lipid Res. (1990) [Pubmed]
  24. Degradation of organochlorine compounds in spent sulfite bleach plant effluents by actinomycetes. Winter, B., Fiechter, A., Zimmermann, W. Appl. Environ. Microbiol. (1991) [Pubmed]
  25. Immunohistochemical expression of peroxisomal enzymes in developing human brain. Houdou, S., Takashima, S., Suzuki, Y. Mol. Chem. Neuropathol. (1993) [Pubmed]
  26. Chronic quercetin exposure affects fatty acid catabolism in rat lung. de Boer, V.C., van Schothorst, E.M., Dihal, A.A., van der Woude, H., Arts, I.C., Rietjens, I.M., Hollman, P.C., Keijer, J. Cell. Mol. Life Sci. (2006) [Pubmed]
  27. Stimulation of potato tuber respiration by cold stress is associated with an increased capacity of both plant uncoupling mitochondrial protein (PUMP) and alternative oxidase. Calegario, F.F., Cosso, R.G., Fagian, M.M., Almeida, F.V., Jardim, W.F., Jezek, P., Arruda, P., Vercesi, A.E. J. Bioenerg. Biomembr. (2003) [Pubmed]
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