Enzymes peroxisomal

Goldsworthy TL, Popp JA. 1987. Chlorinated hydrocarbon-induced peroxisomal enzyme activity in relation to species and organ carcinogenicity. Toxicol Appl Pharmacol 88 225-233. 

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. 

Disorders of peroxisome biogenesis 689 Defects of single peroxisomal enzymes 691... 

Defects of single peroxisomal enzymes. X-linked adre-... 

Racemase deficiency. The biological role of 2-methyl-acyl-CoA racemase has only recently been clarified. This peroxisomal enzyme is essential for certain steps of the oxidation of phytol and bile acid derivatives, which are stereospecific. Biochemically there is accumulation of pristanic acid and C27 bile acid intermediates. Clinical symptoms may include adult-onset peripheral neuropathy, pigmentary degeneration of the retina and liver disease [ 13]. 

Hyperoxaluria type 1 is due to functional efficiency of the liver specific peroxisomal enzyme alanine-glyoxylate aminotransferase. It leads to severe renal failure. The nervous system is not affected. 

Stegink, SJ, Vaughn KC, Kunce CM, Trelease RN. Biochemical, electrophoretic and immunological characterization of peroxisomal enzymes in three soybean organs. Plant Physiol 1987 69 211-220. 

Di(2-ethylhexyl) phthalate (0, 0.5, 1, 2.5 or 5 g/kg per day) was administered to Fischer 344 rats by oral gavage from birth through lactation day 21 and the activity of several peroxisomal enzymes was determined in the livers, kidneys and brains of the females and their offspring (Cimini et al., 1994). No pups survived exposure to doses of 2.5 g/kg per day. Pup growth was impaired at the two lowest doses. In the liver, cyanide-insensitive palmitoyl-CoA oxidase activity showed similar increases in pups and adult females. 

Viswalingam, A. Caldwell, J. (1997) Cinnamyl anthranilate causes co-induction of hepatic microsomal and peroxisomal enzymes in mouse but not rat. Toxicol, appl. Pharmacol., 142, 338-347... 

Kerckaert I, Poll-The , Espeel M, Duran M, Roeleveld AB, Wanders RJA, Roels F (2000) Hepatic peroxisomes in isolated hyperpipecolic acidaemia evidence supporting its classifications as a single peroxisomal enzyme deficiency. Virchows Arch 436 459-465... 

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... 

Wanders RJA, Barth PG, Heymans HSA (2001) Single peroxisomal enzyme deficiencies. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic Molecular Bases of Inherited Disease. McGraw-Hill, New York, pp 3219-3256... 

The receptor protein (52 kDa) is a member of the steroid hormone receptor superfamily, which has a DNA-binding as well as ligand-binding domain. Another receptor, the retinoid X receptor is also involved, and after binding of the peroxisome proliferator, the two receptors form a heterodimer. This binds to a regulatory DNA sequence known as the peroxisome proliferator response element. The end result of the interaction between peroxisome proliferators and this system is that genes are switched on, leading to increases in synthesis (induction) of both microsomal and peroxisomal enzymes and possibly hyperplasia. 

PPAR peroxisome proliferator-activated receptor. Receptor involved in the induction of peroxisomal enzymes other responses to certain chemicals. 

Allantoin is the excretory product in most mammals other than primates. Most fish hydrolyze allantoin to allantoic acid, and some excrete that compound as an end product. However, most continue the hydrolysis to form urea and glyoxylate using peroxisomal enzymes.336 In some invertebrates the urea may be hydrolyzed further to ammonia. In organisms that hydrolyze uric acid to urea or ammonia, this pathway is used only for degradation of purines from nucleotides. Excess nitrogen from catabolism of amino acids either is excreted directly as ammonia or is converted to urea by the urea cycle (Fig. 24-10). 

Rat (albino) 9 mo (F) Hepatic 50 (increased liver weight, morphological changes in bile ducts, lipid filled lysosomes, glycogen depletion, induction of peroxisomal enzymes and cytochrome P-450 system) Mitchell et al. 1985b... 

Rat 2 yr (Fischer- 344) (F) Hepatic 92 (induced peroxisomal enzyme activities) Cattley et al. 1987... 

Dawley) mitochondria, peroxisomes, lipofuscin deposits, conjugated dienes and peroxisomal enzymes) ... 

There are multiple changes in peroxisomal enzymes that occur following exposures to DEHP. Some of the changes are due to peroxisomal proliferation, but induction of specific enzymes is also apparent. 

Other Species. The discussion of hepatic effects in the above subsections is based on effects in rats and mice. Not all animal species are equally susceptible to the hepatic effects of DEHP. Differences in responsiveness are particularly evident with respect to the increases in peroxisomal content of liver cells, induction of peroxisomal enzymes, and increased liver weight (hypertrophy and hyperplasia). Although these responses clearly occur in rats and mice, hamsters are only partially responsive and guinea pigs, and monkeys are refractory. 

Effect Currently there are no simple methods of measuring the effects of DEHP exposure. An increase in liver peroxisomes and peroxisomal enzyme activities appears to be the best marker of effect in rodents. This is not of great value in human studies since there is extensive evidence that humans, as well as primates, are refractory to peroxisome proliferators. Accordingly, research to identify reliable biomarkers for DEHP effects in humans would be useful in order to evaluate the prevalence and magnitude of exposure in an at-risk population. 

Goll V, Alexander E, Viollen-Abadie C, et al. 1999. Comparison of the effects of various peroxisome proliferators on peroxisomal enzyme activities, DNA synthesis, and apoptosis in rat and human hepatocyte cultures. Toxicol Appl Pharmacol 160 21-32. 

Kelley M, Groth-Watson A, Knoble D, et al. 1991. Induction of peroxisomal enzymes by a tetrazole-substituted 2-quinolinylmethoxy leukotriene D4 antagonist [abstract]. Toxicologist 11 184. 

B. G. Lake, T. J. B. Gray, D. F. V. Lewis, J. A. Beamand, K. D. Hodder, R. Purchase, and S. D. Gangolli, Toxicol. Ind. Health, 3, 165 (1987). Structure-Activity Relationships for Induction of Peroxisomal Enzyme Activities by Phthalate Monoesters in Primary Rat Hepatocyte Cultures. 

D-Amino oxidase is a peroxisomal enzyme that catalyzes the oxidative deamination of D-amino acids to give the corresponding a-keto acids, ammonia, and hydrogen peroxide. In this assay, a-ketovaleric acid from D-valine was quantitated. 

Polyamine oxidase is a flavin-dependent peroxisomal enzyme involved in the degradation of polyamines to putrescine. This assay measures the conversion of /V -acetylspermidine to putrescine. 

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