Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vivo administration of nicardipine, a known calcium antagonist, suppressed the clofibrate-evoked induction of activities of peroxisomal enzymes, such as catalase, the peroxisomal fatty acyl-CoA oxidizing system, carnitine acetyltransferase and mitochondrial carnitine palmitoyltransferase in rat liver. On a time-course study, the suppression of induction in the activities of the peroxisomal fatty acyl-CoA oxidizing system and carnitine acetyltransferase was found at 5 days after the treatment, whereas the induction by clofibrate was already observed at 1 day after the treatment, suggesting that in the process of peroxisome induction by clofibrate there might be two steps, i.e., a triggering step and an enhancing step, and nicardipine might act as suppressor for the later step. The precursor-incorporation studies with [3H]leucine showed that the rate of the synthesis of the peroxisomal bifunctional enzyme was increased by 4.2-fold after clofibrate-treatment, whereas nicardipine suppressed this enhancement to only 2.2-fold of the control. The rate of degradation of this enzyme was not affected by any treatment. These results show that nicardipine affects the regulation mechanism of the biosynthesis of this enzyme. Nicardipine showed hardly any suppressive-effect on the hepatic peroxisomal enzyme induction observed in high-fat diet fed rat. Furthermore, the suppression of clofibrate-evoked induction of peroxisomal enzymes was observed also in mice. These interesting findings suggest that there is a difference in the mechanism of peroxisome proliferation and/or the induction of peroxisomal enzymes between clofibrate and physiological conditions, such as high-fat diet feeding. The suppression of drug-induced peroxisome proliferation by calcium antagonists may help in dissecting the causal relationship between the multiple effects mediated by peroxisomal proliferators.
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PMID:Characteristics of the suppressive effect of nicardipine on peroxisome induction in rat liver. 229 37

Treatment of rats by beta,beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a dose- and time-dependent increase in liver peroxisomal enoyl-CoA hydratase and cyanide-insensitive palmitoyl-CoA oxidation with a concomitant increase in the volume density of peroxisomes as determined by morphometry. The induced peroxisomal proliferation was sustained as long as treatment was maintained and was accompanied by an increase in liver weight. Incubation of cultured rat hepatocytes in the presence of MEDICA 16 added to the culture medium resulted in a dose-dependent increase in peroxisomal beta-oxidation activities with a concomitant elevation of the volume density of peroxisomes. The induction of peroxisomal proliferation by MEDICA 16 in culture could be prevented in the presence of carnitine palmitoyltransferase inhibitors added to the culture medium, e.g. 2-bromopalmitate, 2-tetradecylglycidic acid or 2-[5-(4-chlorophenyl)-pentyl]oxirane-2-carboxylate. The induction of liver peroxisomes by MEDICA 16 conforms to the previously defined requirement for an amphipathic carboxylate in initiating peroxisomal proliferation. The prevention of peroxisomal proliferation by carnitine acyltransferase inhibitors may implicate the involvement of this acyltransferase in the induction of peroxisomal proliferation by xenobiotic or native amphipathic carboxylates.
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PMID:The induction of liver peroxisomal proliferation by beta,beta'-methyl-substituted hexadecanedioic acid (MEDICA 16). 317 72

The activities and amounts of enzyme proteins of peroxisomal beta-oxidation in Japanese children with Zellweger syndrome were investigated. Cyanide-insensitive fatty acid oxidation, peroxisomal enoyl-CoA hydratase and 3-oxoacyl-CoA thiolase activities were not detectable in liver tissue at autopsy, whereas the activities of mitochondrial enoyl-CoA hydratase, 3-oxoacyl-CoA thiolase and carnitine palmitoyltransferase were similar to those in the healthy controls. On immunoblot analysis, immunoreactive proteins of peroxisomal acyl-CoA oxidase, bifunctional protein and 3-oxoacyl-CoA thiolase were not detected in the livers, kidneys and fibroblasts from the patients. Proteins of catalase and some enzymes of mitochondrial fatty acid oxidation were similar as in normal controls. These data indicate that increased levels of very-long-chain fatty acids in Zellweger syndrome are due to the lack of the enzyme proteins of peroxisomal beta-oxidation.
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PMID:Deficient activities and proteins of peroxisomal beta-oxidation enzymes in infants with Zellweger syndrome. 351 3

Disorders of glycogen, lipid or mitochondrial metabolism may cause two main clinical syndromes, namely (1) progressive weakness (eg, acid maltase, debrancher enzyme, and brancher enzyme deficiencies among the glycogenoses; long- and very-long-chain acyl-CoA dehydrogenase (LCAD, VLCAD), and trifunctional enzyme deficiencies among the fatty acid oxidation (FAO) defects; and mitochondrial enzyme deficiencies) or (2) acute, recurrent, reversible muscle dysfunction with exercise intolerance and acute muscle breakdown or myoglobinuria (with or without cramps) (eg, phosphorylase (PPL), phosphorylase b kinase (PBK), phosphofructokinase (PFK), phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGAM), and lactate dehydrogenase (LDH) among the glycogenoses and carnitine palmitoyltransferase II (CPT II) deficiency among the disorders of FAO or (3) both (eg, PPL, PBK, PFK among the glycogenoses; LCAD, VLCAD, short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD), and trifunctional enzyme deficiencies among the FAO defects; and multiple mitochondrial DNA (mtDNA) deletions). Myoadenylate deaminase deficiency, a purine nucleotide cycle defect, is somewhat controversial and is characterized by exercise-related cramps leading rarely to myoglobinuria.
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PMID:Metabolic myopathies. 879 43

The primary presentations of neuromuscular disease in the newborn period are hypotonia and weakness. Although metabolic myopathies are inherited disorders that present from birth and may present with subtle to marked neonatal hypotonia, a number of these defects are diagnosed classically in childhood, adolescence, or adulthood. Disorders of glycogen, lipid, or mitochondrial metabolism may cause three main clinical syndromes in muscle, namely, (1) progressive weakness with hypotonia (e.g., acid maltase, debrancher enzyme, and brancher enzyme deficiencies among the glycogenoses; carnitine uptake and carnitine acylcarnitine translocase defects among the fatty acid oxidation (FAO) defects; and cytochrome oxidase deficiency among the mitochondrial disorders) or (2) acute, recurrent, reversible muscle dysfunction with exercise intolerance and acute muscle breakdown or myoglobinuria (with or without cramps), e.g., phosphorylase, phosphofructokinase, and phosphoglycerate kinase among the glycogenoses and carnitine palmitoyltransferase II deficiency among the disorders of FAO or (3) both (e.g., long-chain or very long-chain acyl coenzyme A (CoA) dehydrogenase, short-chain L-3-hydroxyacyl-CoA dehydrogenase, and trifunctional protein deficiencies among the FAO defects). Episodes of exercise-induced myoglobinuria tend to present in later childhood or adolescence; however, myoglobinuria in the first year of life may occur in FAO disorders during catabolic crises precipitated by fasting or infection. The following is a survey of genetic disorders of glycogen and lipid metabolism resulting in myopathy, focusing primarily on those defects, to date, that have presented in the neonatal or early infancy period. Disorders of mitochondrial metabolism are discussed in another chapter.
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PMID:Neonatal metabolic myopathies. 1033 65

The spectrum of clinical presentation of fatty acid oxidation defects (FAOD) continues to expand. One FAOD, L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been associated with liver disease in pregnancies involving a heterozygous mother carrying an affected fetus. Hepatic carnitine palmitoyltransferase (CPT I) deficiency typically presents as a Reyelike syndrome in children between 8 and 18 mo. of age. We have investigated a family in which the mother developed liver disease consistent with acute fatty liver of pregnancy (AFLP) and hyperemesis gravidarum in her two successive pregnancies. Neither child nor their mother was found to carry the common LCHAD G1528C mutation. Both children were subsequently shown to have absent activity of CPT I. This is the first report of CPT I deficiency presenting as maternal illness in pregnancy.
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PMID:Hepatic carnitine palmitoyltransferase I deficiency presenting as maternal illness in pregnancy. 1062 76

We evaluated the effects of dietary fat type on fat metabolism and deposition in broiler chickens. Birds were fed diets containing either 8 g dietary saturated (beef tallow) or polyunsaturated fat (sunflower oil)/100 g for 32 d. The abdominal fat deposition of chickens fed the sunflower oil-enriched diet was significantly lower than that of chickens fed the tallow-enriched diet (2.63 +/- 0.47 versus 3.03 +/- 0.44 g/100 g live wt.; P = 0.033). The specific activities of heart carnitine palmitoyltransferase I and L-3-hydroxyacyl-CoA dehydrogenase were higher (P < or = 0.03) in chickens fed the sunflower oil-enriched diets, indicating a greater rate of beta-oxidation. Liver fatty acid synthetase activity was lower (P = 0.01) in chickens fed the sunflower oil-enriched diet, suggesting reduced hepatic lipogenesis in this group. Postprandial plasma triglyceride levels were significantly lower (P < 0.05) in birds fed the sunflower oil-enriched diet, indicating a higher rate of dietary lipid clearance from the bloodstream to tissues. In conclusion, the lower fat deposition observed in broilers fed sunflower oil-enriched diets appears to be the net result of an increased rate of lipid catabolism and lower rate of fatty acid synthesis despite higher dietary fat absorption.
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PMID:Abdominal fat deposition and fatty acid synthesis are lower and beta-oxidation is higher in broiler chickens fed diets containing unsaturated rather than saturated fat. 1111 Aug 64

We compared the ability of rat and human hepatocytes to respond to fenofibric acid and a novel potent phenylacetic acid peroxisome proliferator-activated receptor (PPAR) alpha agonist (compound 1). Fatty acyl-CoA oxidase (FACO) activity and mRNA were increased after treatment with either fenofibric acid or compound 1 in rat hepatocytes. In addition, apolipoprotein CIII mRNA was decreased by both fenofibric acid and compound 1 in rat hepatocytes. Both agonists decreased apolipoprotein CIII mRNA in human hepatocytes; however, very little change in FACO activity or mRNA was observed. Furthermore, other peroxisome proliferation (PP)-associated genes including peroxisomal 3-oxoacyl-CoA thiolase (THIO), peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD), peroxisomal membrane protein-70 (PMP-70) were not regulated by PPAR alpha agonists in human hepatocytes. Moreover, other genes that are regulated by PPAR alpha ligands in human hepatocytes such as mitochondrial HMG-CoA synthase and carnitine palmitoyl transferase-1 (CPT-1) were also regulated in HepG2 cells by PPAR alpha agonists. Several stably transfected HepG2 cell lines were established that overexpressed human PPAR alpha to levels between 6- and 26-fold over normal human hepatocytes. These PPAR alpha-overexpressing cells had higher basal mRNA levels of mitochondrial HMG-CoA synthase and CPT-1; however, basal FACO mRNA levels and other PP-associated genes including THIO, HD, or PMP-70 mRNA were not substantially affected. In addition, FACO, THIO, HD, and PMP-70 mRNA levels did not increase in response to PPAR alpha agonist treatment in the PPAR alpha-overexpressing cells, although mitochondrial HMG-CoA synthase and CPT-1 mRNAs were both induced. These results suggest that other factors besides PPAR alpha levels determine the species-specific response of human and rat hepatocytes to the induction of PP.
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PMID:Differential gene regulation in human versus rodent hepatocytes by peroxisome proliferator-activated receptor (PPAR) alpha. PPAR alpha fails to induce peroxisome proliferation-associated genes in human cells independently of the level of receptor expresson. 1141 1