Peroxisomal beta-oxidation

M (32% increase in liver weights 178% increase in peroxisomal beta-oxidation enzyme activity)... 

A 32% increase in liver weights, along with a 187% increase in peroxisomal beta-oxidation activity, was noted in rats exposed to 1,000 mg/kg/day MIL-H-5606 for 26 days (Mattie et al. 1993). The toxicological significance of the changes in peroxisomal enzyme activities is unclear. 

Mineral Oil Hydraulic Fluids. No studies regarding hepatic effects in humans following inhalation, oral, or dermal exposure to mineral oil hydraulic fluids were located. In an animal study, histopathological examination of the livers from rats exposed by inhalation to <1.0 mg/m3 of the water-in-oil emulsion hydraulic fluid Houghto-Safe 5047F for 90 days, 23 hours/day, showed no treatment-related lesions (Kinkead et al. 1991). Animal data for oral exposure are limited to one study where rats were exposed to MIL-H-5606 at 1,000 mg/kg/day for 26 days (Mattie et al. 1993). Increases in liver weight and peroxisomal beta-oxidation activity were observed. 

To date there are no true inborn errors associated with essential fatty acid metabolism. However, we do know that the final step of DHA formation is the peroxisomal beta-oxidation of a homologous C24 fatty acid [7]. Consequently, patients with a generalised defect of peroxisomal function, such as Zellweger syndrome, are prone to develop deficiencies of essential fatty acids including DHA [9]. 

Group 2 contains the single peroxisomal enzyme deficiencies [14]. This group is also subdivided in different classes, including the peroxisomal beta-oxidation deficiencies (X-linked adrenoleucodystrophy, X-ALD), acyl-CoA oxidase 1 deficiency... 

Rao MS, Reddy JK. Peroxisomal beta-oxidation and steatohepatitis. Semin Live Dis 2001 21 43-55. 

Hashimoto T. (1996) Peroxisomal beta-oxidation enzymology and molecular biology. Ann. N. Y. Acad. Sci. 804, 86-98. 

Isenberg JS, Kamendulis LM, Smith JH, et al. 2000. Effects of Di-2-Ethlhexyl phthalate (DEHP) on gap-junctional intercellular communication (GJIC), DNA synthesis, and peroxisomal beta oxidation (PBOX) inrat, mouse, and hamster liver. Toxicol Sci 56 73-85. 

Dreyer, C., Krey, G., Keller, H., Givel, F., Helftenbein, G., and Wahli, W. (1992). Control of the Peroxisomal Beta-Oxidation pathway by a Novel Family of Nuclear Hormone Receptors. Cell 68, 879-887. 

Ferdinandusse, S., Denis, S., Mooijer, PA. etal., Identification of the peroxisomal beta-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid, J. Lipid Res., 42, 1987, 2001. 

Yonssef JA, Song WO, and Badr MZ (1997) Mitochondrial, bnt not peroxisomal, beta-oxidation of fatty acids is conserved in coenzyme A-deflcient rat liver. Molecular and Cellular Biochemistry 175,37-42. 

Reddy JK. Nonalcoholic steatosis and steatohepatitis. III. Peroxisomal beta-oxidation, PEAR alpha, and steatohepatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2001 281 G1333-G1339. 

The feeding of an EPA-free source of supplementary DHA (from algae) to human volunteers indicated a metabolic retroconversion of DHA to EPA (Conquer and Holub, 1996, 1997). Previous animal and in vitro studies in isolated rat liver cells have demonstrated that DHA can be retroconverted to EPA, and that this retroconversion is a peroxisomal function (Schlenk et al., 1969 Gronn et al., 1991). Studies in isolated rat liver cells by Schlenk et al., 1969 have also indicated that the resultant EPA can be chain-elongated to DPA (22 5n-3) for subsequent esterification into cellular lipids. An acyl-CoA oxidase has been identified as the enzyme responsible for the chain shortening of DHA in the peroxisomal beta-oxidation of PUFA in human fibroblasts (Christensen et al., 1993). The aforementioned in vivo human studies have estimated the extent of retroconversion of DHA to EPA to be approximately 10% (Conquer and Holub, 1996, 1997). 

Christensen, E., Woldseth, B., Hagve, T.A., Poll-The, B.T., Wanders, R.J., Sprecher, H., Stokke, O. and Christophersen, B.O. (1993) Peroxisomal beta-oxidation of polyunsaturated long chain fatty acids in human fibroblasts. The polyunsaturated and the saturated long chain fatty acids are retroconverted by the same acyl-CoA oxidase. Scand. J. Clin. Lab. Invest. 215 S61-S74. 

Jia, Y, Qi, C., Zhang, Z., Hashimoto, T., Rao, M. S., Huyghe, S., Suzuki, Y, Van Veldhoven, P. P., Baes, M., and Reddy, J. K. (2003). Overexpression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D-forms of enoyl-CoA hydratase/dehydrogenase enzymes of peroxisomal beta-oxidation system. J Biol Chem 278, 47232-47239. 

Hashimoto, T., Peroxisomal beta-Oxidation Enzymes, Cell Biochem. Biophys., 32 63-72, 2000. 

Peroxisomal beta-oxidation of fatty acids (U=umol. dichlorofluoroscein/min). 

Peroxisomal beta oxidation. In animal cells p oxidation is primarily a mitochondrial process, but it also takes place to a limited extent within peroxisomes and within the endoplasmic reticulum. " ... 

Reddy, J.K. and T. Hashimoto (2001). Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha An adaptive metabolic system. Anna. Rev. Nutr. 21, 193-230. 

Foxworthy, P.S. Perry, D.N. Eacho, P.I. Induction of peroxisomal beta-oxidation by nonsteroidal anti-inflammatory drugs. Toxicol. Appl. Pharmacol. 1993, 1118, 272 274. 

Infante, J.P., and Huszagh, V.A. (2001) Zellweger Syndrome Knockout Mouse Models Challenge Putative Peroxisomal Beta-Oxidation Involvement in Docosahexaenoic Acid (22 6n-3)... 

Infante, J.P., Tschanz, C.L., Shaw, N., Michaud, Ai., Lawrence, P., and Brenna, J.T. (2002) Straight-Chain Acyl-CoA Oxidase Knockout Mouse Accumulates Extremely Long Chain Fatty Acids from Alpha-Linolenic Acid Evidence for Runaway Carousel-Type Enzyme Kinetics in Peroxisomal Beta-Oxidation Diseases. MoZ. Genet. Metab. 75,108-119. 

Sleboda, J., Pourfarzam, M., Bartlett, K. Osmundsen, H. (1995) Biochim. Biophys. Acta 1258, 309-318. Effects of added l-cami1ine, acelyl-coa and coa on peroxisomal beta- oxidation of [U- C]hexa-decanoate by isolated peroxisomal fractions. 

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