Genomes and Genes
acyl coa oxidase
Summary: An enzyme that catalyzes the first and rate-determining steps of peroxisomal beta-oxidation of fatty acids. It acts on COENZYME A derivatives of fatty acids with chain lengths from 8 to 18, using FLAVIN-ADENINE DINUCLEOTIDE as a cofactor.
- Qi C, Zhu Y, Pan J, Usuda N, Maeda N, Yeldandi A, et al. 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. J Biol Chem. 1999;274:15775-80 pubmed..This blunting of peroxisome proliferative response is attributed to the absence of L-PBE protein in L-PBE-/- mouse liver, because all other proteins are induced essentially to the same extent in both wild type and L-PBE-/- mice. ..
- Fan C, Pan J, Usuda N, Yeldandi A, Rao M, Reddy J. 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. J Biol Chem. 1998;273:15639-45 pubmed..These observations implicate acyl-CoA and other putative substrates for AOX, as biological ligands for PPARalpha; thus, a normal AOX gene is indispensable for the physiological regulation of PPARalpha. ..
- Fan C, Pan J, Chu R, Lee D, Kluckman K, Usuda N, et al. Hepatocellular and hepatic peroxisomal alterations in mice with a disrupted peroxisomal fatty acyl-coenzyme A oxidase gene. J Biol Chem. 1996;271:24698-710 pubmed..These observations demonstrate links among peroxisomal beta-oxidation, development of severe microvesicular fatty liver, peroxisome assembly, cell death, and cell proliferation in liver. ..
- Glauert H, Eyigor A, Tharappel J, Cooper S, Lee E, Spear B. Inhibition of hepatocarcinogenesis by the deletion of the p50 subunit of NF-kappaB in mice administered the peroxisome proliferator Wy-14,643. Toxicol Sci. 2006;90:331-6 pubmed
- van Roermund C, Tabak H, Van den Berg M, Wanders R, Hettema E. Pex11p plays a primary role in medium-chain fatty acid oxidation, a process that affects peroxisome number and size in Saccharomyces cerevisiae. J Cell Biol. 2000;150:489-98 pubmed..Our observations suggest that the MCFA oxidation pathway regulates the level of a signaling molecule that modulates the number of peroxisomal structures in a cell. ..
- Nakajima Y, Miyahara I, Hirotsu K, Nishina Y, Shiga K, Setoyama C, et al. Three-dimensional structure of the flavoenzyme acyl-CoA oxidase-II from rat liver, the peroxisomal counterpart of mitochondrial acyl-CoA dehydrogenase. J Biochem. 2002;131:365-74 pubmed..The crevice for binding the fatty acyl chain is 28 A long and 6 A wide, large enough to accommodate the C23 acyl chain. ..
- Chao P, Chao C, Lin F, Huang C. Oxidized frying oil up-regulates hepatic acyl-CoA oxidase and cytochrome P450 4 A1 genes in rats and activates PPARalpha. J Nutr. 2001;131:3166-74 pubmed..The results support our hypothesis that dietary OFO, by activating PPARalpha, up-regulates the expression of PPARalpha downstream genes and alters lipid metabolism in rats. ..
- Titorenko V, Smith J, Szilard R, Rachubinski R. Pex20p of the yeast Yarrowia lipolytica is required for the oligomerization of thiolase in the cytosol and for its targeting to the peroxisome. J Cell Biol. 1998;142:403-20 pubmed..Translocation of the thiolase homodimer into the peroxisomal matrix would release Pex20p monomers back to the cytosol, thereby permitting a new cycle of binding-oligomerization-targeting-release for Pex20p and thiolase...
- Goll V, Viollon Abadie C, Nicod L, Richert L. Peroxisome proliferators induce apoptosis and decrease DNA synthesis in hepatoma cell lines. Hum Exp Toxicol. 2000;19:193-202 pubmed..e. inhibition of both spontaneous and TGFbeta-induced apoptosis and increases in DNA synthesis in rat hepatocytes, and unchanged mitosis-apoptosis balance in human hepatocytes. ..
- Sülzle A, Hirche F, Eder K. Thermally oxidized dietary fat upregulates the expression of target genes of PPAR alpha in rat liver. J Nutr. 2004;134:1375-83 pubmed..Determination of gene expression of acyl CoA oxidase and activity of catalase confirmed that oxidized fats caused peroxisome proliferation in the liver...
- Hoivik D, Qualls C, Mirabile R, Cariello N, Kimbrough C, Colton H, et al. Fibrates induce hepatic peroxisome and mitochondrial proliferation without overt evidence of cellular proliferation and oxidative stress in cynomolgus monkeys. Carcinogenesis. 2004;25:1757-69 pubmed..A mild induction in the mRNA levels of cellular beta-oxidation and detoxification enzymes (e.g. acyl CoA oxidase, thioredoxin reductase) was observed...
- Kassam A, Capone J, Rachubinski R. The short heterodimer partner receptor differentially modulates peroxisome proliferator-activated receptor alpha-mediated transcription from the peroxisome proliferator-response elements of the genes encoding the peroxisomal beta-oxidation enzymes ac. Mol Cell Endocrinol. 2001;176:49-56 pubmed..This is the first demonstration of positive transcriptional activity attributable to SHP. Together, these results suggest that SHP can modulate PPARalpha/RXRalpha-mediated transcription in a response element-specific manner. ..
- Nanji A, Dannenberg A, Jokelainen K, Bass N. Alcoholic liver injury in the rat is associated with reduced expression of peroxisome proliferator-alpha (PPARalpha)-regulated genes and is ameliorated by PPARalpha activation. J Pharmacol Exp Ther. 2004;310:417-24 pubmed..binding protein (L-FABP), peroxisome proliferator-activated receptor-alpha (PPARalpha), and peroxisomal fatty acyl CoA oxidase (FACO)...
- Bocchetti R, Fattorini D, Pisanelli B, Macchia S, Oliviero L, Pilato F, et al. Contaminant accumulation and biomarker responses in caged mussels, Mytilus galloprovincialis, to evaluate bioavailability and toxicological effects of remobilized chemicals during dredging and disposal operations in harbour areas. Aquat Toxicol. 2008;89:257-66 pubmed publisher..Such biological responses included levels of metallothioneins, activity of acyl CoA oxidase (AOX) as a marker of peroxisome proliferation, oxidative stress biomarkers (content of glutathione, enzymatic ..
- Minoura H, Takeshita S, Kimura C, Hirosumi J, Takakura S, Kawamura I, et al. Mechanism by which a novel non-thiazolidinedione peroxisome proliferator-activated receptor gamma agonist, FK614, ameliorates insulin resistance in Zucker fatty rats. Diabetes Obes Metab. 2007;9:369-78 pubmed..FK614 significantly increased the expression levels of acyl CoA oxidase, a PPAR-responsive gene, and adipocyte fatty acid-binding protein (aP2), an adipocyte differentiation marker ..
- Sanguino E, Ramón M, Michalik L, Wahli W, Alegret M, Sanchez R, et al. Lack of hypotriglyceridemic effect of gemfibrozil as a consequence of age-related changes in rat liver PPARalpha. Biochem Pharmacol. 2004;67:157-66 pubmed..We hypothesize that the decrease in hepatic PPARalpha can be related to a state of leptin resistance present in old animals. ..
- Lehr H, Germann G, McGregor G, Migeod F, Roesen P, Tanaka H, et al. Consensus meeting on "Relevance of parenteral vitamin C in acute endothelial dependent pathophysiological conditions (EDPC)". Eur J Med Res. 2006;11:516-26 pubmed..Vitamin C directly enhances the activity of nitric oxide synthase, the acyl CoA oxidase system and inhibits the actions of proinflammatory lipids...
- Haushalter R, Groff D, Deutsch S, The L, Chavkin T, Brunner S, et al. Development of an orthogonal fatty acid biosynthesis system in E. coli for oleochemical production. Metab Eng. 2015;30:1-6 pubmed publisher..Finally, functional expression of these large enzyme complexes in E. coli will enable their study without culturing the native organisms. ..
- Ferdinandusse S, Denis S, Dacremont G, Wanders R. Studies on the metabolic fate of n-3 polyunsaturated fatty acids. J Lipid Res. 2003;44:1992-7 pubmed..This DHA-CoA then preferentially moves back, probably as free fatty acid, to the ER, where it is incorporated into membrane lipids. ..
- JimÃ©nez M, Bocos C, Panadero M, Herrera E. Fish oil diet in pregnancy and lactation reduces pup weight and modifies newborn hepatic metabolic adaptations in rats. Eur J Nutr. 2017;56:409-420 pubmed publisher..Maternal intake of high n-3 LCPUFA retards postnatal development, which could be the result of impaired ARA synthesis, and affects hepatic metabolic adaptations to extrauterine life. ..
- Zhao Y, Yang L, Huang Z, Lin L, Zheng G. Synergistic effects of caffeine and catechins on lipid metabolism in chronically fed mice via the AMP-activated protein kinase signaling pathway. Eur J Nutr. 2017;56:2309-2318 pubmed publisher..This study indicates that chronic intake of both caffeine and catechins can synergistically contribute to prevention of obesity and lifestyle-related diseases. ..
- Gurvitz A, Hiltunen J, Erdmann R, Hamilton B, Hartig A, Ruis H, et al. Saccharomyces cerevisiae Adr1p governs fatty acid beta-oxidation and peroxisome proliferation by regulating POX1 and PEX11. J Biol Chem. 2001;276:31825-30 pubmed..We conclude that overlapping ORE and UAS1 elements in conjunction with their binding factors Pip2p-Oaf1p and Adr1p coordinate the carbon flux through beta-oxidation with peroxisome proliferation. ..
- Atshaves B, McIntosh A, Storey S, Landrock K, Kier A, Schroeder F. High dietary fat exacerbates weight gain and obesity in female liver fatty acid binding protein gene-ablated mice. Lipids. 2010;45:97-110 pubmed publisher..Taken together, these results indicate loss of L-FABP exacerbates weight gain and/or obesity in response to high dietary fat. ..
- Wan Y, Saleem R, Ratushny A, Roda O, Smith J, Lin C, et al. Role of the histone variant H2A.Z/Htz1p in TBP recruitment, chromatin dynamics, and regulated expression of oleate-responsive genes. Mol Cell Biol. 2009;29:2346-58 pubmed publisher..While these new nucleosomes do not incorporate Htz1p, the initial presence of Htz1p appears to mark the promoter for sustained gene expression and the recruitment of TATA-binding protein. ..
- Cansell M, Battin A, Degrace P, Gresti J, Clouet P, Combe N. Early dissimilar fates of liver eicosapentaenoic acid in rats fed liposomes or fish oil and gene expression related to lipid metabolism. Lipids. 2009;44:237-47 pubmed publisher..The quasi absence of EPA in hepatic PL of liposome-treated rats on the short term could result from increased beta-oxidation activities through metabolic regulations induced by more available free EPA and other PUFA. ..
- Sommer J, Mahli A, Freese K, Schiergens T, Kuecuekoktay F, Teufel A, et al. Analysis of molecular mechanisms of 5-fluorouracil-induced steatosis and inflammation in vitro and in mice. Oncotarget. 2017;8:13059-13072 pubmed publisher..Our newly developed models can be used to gain further insight into the pathogenesis of 5-FU-induced steatohepatitis and to develop therapeutic strategies to inhibit its development and progression. ..
- Iannelli P, Zarrilli V, Varricchio E, Tramontano D, Mancini F. The dietary antioxidant resveratrol affects redox changes of PPARalpha activity. Nutr Metab Cardiovasc Dis. 2007;17:247-56 pubmed..Caution is therefore warranted before drawing conclusions about the potential benefits of RES for human health. ..
- Ko C, O Rourke S, Huang L. A fish oil diet produces different degrees of suppression of apoB and triglyceride secretion in human apoB transgenic mouse strains. J Lipid Res. 2003;44:1946-55 pubmed..In summary, differential effects of FO on plasma apoB and TG levels in B6 and FVB x B6 HuBTg mice were associated with strain differences in hepatic apoB and TG secretion and in peroxisomal beta-oxidation. ..
- Reiser K, Davis M, Hynes M. AoxA is a major peroxisomal long chain fatty acyl-CoA oxidase required for beta-oxidation in A. nidulans. Curr Genet. 2010;56:139-50 pubmed publisher..It is proposed that there are additional peroxisomal beta-oxidation pathways in A. nidulans, which include fatty acyl-CoA dehydrogenases with a partially overlapping substrate range and include a pathway for short chain FA. ..
- Chu R, Zhang W, Lim H, Yeldandi A, Herring C, Brumfield L, et al. Profiling of acyl-CoA oxidase-deficient and peroxisome proliferator Wy14,643-treated mouse liver protein by surface-enhanced laser desorption/ionization ProteinChip Biology System. Gene Expr. 2002;10:165-77 pubmed..This SELDI method offers several technical advantages for detection of differentially expressed proteins, including ease and speed of screening, no need for chromatographic processing, and small sample size. ..
- Poynter M, Daynes R. Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging. J Biol Chem. 1998;273:32833-41 pubmed..Our results suggest that PPARalpha and the genes under its control play a role in the evolution of oxidative stress excesses observed in aging. ..
- Sun L, Zhi Z, Chen L, Zhou Q, Li X, Gan W, et al. SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p. Cancer Lett. 2017;409:104-115 pubmed publisher..In conclusion, our study demonstrated a functional role of the SIRT1/miR-15b-5p/ACOX1 axis in CRC metastasis and suggested a potential target for metastatic CRC therapy. ..
- Saad D, Soliman M, Baiomy A, Yassin M, El Sawy H. Effects of Karela (Bitter Melon; Momordica charantia) on genes of lipids and carbohydrates metabolism in experimental hypercholesterolemia: biochemical, molecular and histopathological study. BMC Complement Altern Med. 2017;17:319 pubmed publisher..b>Acyl CoA oxidase (ACO), fatty acids synthase (FAS), sterol responsible element binding protein-1c (SREBP1c), 3-hydroxy-3-..
- Jeng L, Velmurugan B, Hsu H, Wen S, Shen C, Lin C, et al. Fenofibrate induced PPAR alpha expression was attenuated by oestrogen receptor alpha overexpression in Hep3B cells. Environ Toxicol. 2018;33:234-247 pubmed publisher..This study illustrates that PPARÎ± expression and function were negatively regulated by ERÎ± expression in Hep3B cells. ..
- Tokuoka K, Nakajima Y, Hirotsu K, Miyahara I, Nishina Y, Shiga K, et al. Three-dimensional structure of rat-liver acyl-CoA oxidase in complex with a fatty acid: insights into substrate-recognition and reactivity toward molecular oxygen. J Biochem. 2006;139:789-95 pubmed
- Varanasi U, Chu R, Chu S, Espinosa R, LeBeau M, Reddy J. Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter analysis, and chromosomal localization. Proc Natl Acad Sci U S A. 1994;91:3107-11 pubmed..This ACOX gene has been mapped to chromosome 17q25 by in situ hybridization, using a biotinlabeled probe. ..
- Trickett J, Patel D, Knight B, Saggerson E, Gibbons G, Pease R. Characterization of the rodent genes for arylacetamide deacetylase, a putative microsomal lipase, and evidence for transcriptional regulation. J Biol Chem. 2001;276:39522-32 pubmed..This hypothesis is supported by parallel changes in AADA gene expression in animals with insulin-deficient diabetes and following treatment with orotic acid. ..
- Shimozawa N, Zhang Z, Suzuki Y, Imamura A, Tsukamoto T, Osumi T, et al. Functional heterogeneity of C-terminal peroxisome targeting signal 1 in PEX5-defective patients. Biochem Biophys Res Commun. 1999;262:504-8 pubmed..It seems apparent that -AKL and -KANL are poorer variants of PTS1 and are likely to be more susceptible to effects of mutation of its receptor, Pex5p. ..
- Hooks M, Kellas F, Graham I. Long-chain acyl-CoA oxidases of Arabidopsis. Plant J. 1999;20:1-13 pubmed..Seedlings with long-chain oxidase activity reduced down to 30% of wild-type levels germinated and established normally; however, reduced root growth appeared to be a general feature of antisense AtACX1 plants. ..
- Rao M, Reddy J. Peroxisomal beta-oxidation and steatohepatitis. Semin Liver Dis. 2001;21:43-55 pubmed
- Jeong S, Kim M, Han M, Lee H, Ahn J, Kim M, et al. Fenofibrate prevents obesity and hypertriglyceridemia in low-density lipoprotein receptor-null mice. Metabolism. 2004;53:607-13 pubmed..Therefore, our results suggest that alterations in hepatic PPARalpha action by fenofibrate seem to suppress diet-induced obesity and severe hypertriglyceridemia caused by LDLR deficiency in male mice. ..
- Oaxaca Castillo D, Andreoletti P, Vluggens A, Yu S, Van Veldhoven P, Reddy J, et al. Biochemical characterization of two functional human liver acyl-CoA oxidase isoforms 1a and 1b encoded by a single gene. Biochem Biophys Res Commun. 2007;360:314-9 pubmed..ACOX1a seems to be more labile and exhibits only 50% specific activity toward palmitoyl-CoA as compared to ACOX1b. ..
- Zhang L, Li H, Gao L, Qi Y, Fu W, Li X, et al. Acyl-CoA oxidase 1 is involved in ?-decalactone release from peach (Prunus persica) fruit. Plant Cell Rep. 2017;36:829-842 pubmed publisher..This study revealed the vital function of PpACX1 in ?-decalactone biosynthesis in peach fruit. ..
- Fujiwara C, Imamura A, Hashiguchi N, Shimozawa N, Suzuki Y, Kondo N, et al. Catalase-less peroxisomes. Implication in the milder forms of peroxisome biogenesis disorder. J Biol Chem. 2000;275:37271-7 pubmed..Thus, we conclude that in 65TS, catalase-less peroxisomes are the direct precursors of peroxisomes...
- Cabrero A, Jové M, Planavila A, Merlos M, Laguna J, Vázquez Carrera M. Down-regulation of acyl-CoA oxidase gene expression in heart of troglitazone-treated mice through a mechanism involving chicken ovalbumin upstream promoter transcription factor II. Mol Pharmacol. 2003;64:764-72 pubmed..Overall, the findings presented here show that 10 days of troglitazone treatment decreased expression of the ACO gene through a mechanism involving the transcriptional repressor COUP-TF II. ..
- Yeon J, Choi K, Baik S, Kim K, Lim H, Park K, et al. Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2004;19:799-804 pubmed..Reduced expression of PPAR-alpha and AOX was observed even before definite steatosis had developed. The alteration of peroxisomal fatty acid metabolism may have an important role in the development of NAFLD. ..
- Dyroy E, Wergedahl H, Skorve J, Gudbrandsen O, Songstad J, Berge R. Thia fatty acids with the sulfur atom in even or odd positions have opposite effects on fatty acid catabolism. Lipids. 2006;41:169-77 pubmed..In summary, the position of the sulfur atom in the alkyl chain, especially whether it is placed in the even or odd position, is crucial for the biological effect of the thia FA. ..
- Tugwood J, Aldridge T, Lambe K, Macdonald N, Woodyatt N. Peroxisome proliferator-activated receptors: structures and function. Ann N Y Acad Sci. 1996;804:252-65 pubmed..Studies are ongoing to clarify this further, but human polymorphism may go some way towards explaining the apparent paradox that active PPAR alpha receptors can be isolated from an "unresponsive" species. ..
- Bell D, Bars R, Gibson G, Elcombe C. Localization and differential induction of cytochrome P450IVA and acyl-CoA oxidase in rat liver. Biochem J. 1991;275 ( Pt 1):247-52 pubmed..The results demonstrate that these proteins are induced in a dose-dependent manner in the same, spatially distinct, sensitive region of the liver lobule...
- Tang X, Ma H, Zou S, Chen W. Effects of dehydroepiandrosterone (DHEA) on hepatic lipid metabolism parameters and lipogenic gene mRNA expression in broiler chickens. Lipids. 2007;42:1025-33 pubmed..Overall, the results of the present study indicated that DHEA accelerated lipid catabolism by direct regulation of hepatic lipid metabolism and by induction of relevant gene expression. ..
- Zhu M, Lee G, Ding L, Hu J, Qiu G, de Cabo R, et al. Adipogenic signaling in rat white adipose tissue: modulation by aging and calorie restriction. Exp Gerontol. 2007;42:733-44 pubmed..Overall these results suggest that CR increased the expression of adipogenic factors, and maintained the differentiated state of adipocytes, which is critically important for adiponectin biosynthesis and insulin sensitivity. ..
- Wache Y, Laroche C, Bergmark K, Møller Andersen C, Aguedo M, Le Dall M, et al. Involvement of acyl coenzyme A oxidase isozymes in biotransformation of methyl ricinoleate into gamma-decalactone by Yarrowia lipolytica. Appl Environ Microbiol. 2000;66:1233-6 pubmed..On the contrary, the Deltapox2 Deltapox3 Deltapox4 Deltapox5 multidisrupted strain did not grow or biotransform methyl ricinoleate into gamma-decalactone, demonstrating that Aox4p is essential for the biotransformation. ..