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)

The effects of sodium 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA), a potent inhibitor of carnitine palmitoyltransferase I, on fatty acid oxidation were investigated using fibroblasts from control subjects and from patients with peroxisomal disorders. [1-14C]Palmitate oxidation was inhibited by 8% of the control value when 15 microM POCA was added to the medium. The inhibition by POCA was significantly (P less than 0.05) stronger in fibroblasts from patients with Zellweger syndrome or with neonatal adrenoleukodystrophy, in which peroxisomes and peroxisomal beta-oxidation enzymes were absent. However, the inhibition in fibroblasts from patients with X-linked adrenoleukodystrophy, in which a specific defect of peroxisomal lignoceroyl-CoA synthetase was speculated, was similar to that in the controls. [1-14C]Lignocerate oxidation was not influenced by the addition of POCA, in samples from the controls and from the patients. These results indicate that peroxisomes account for a small but demonstrable proportion of palmitate oxidation, and add new evidence to the concept that lignocerate is oxidized exclusively in the peroxisomes. Our findings also support the hypotheses that the activity of palmitoyl-CoA synthetase and the enzymes of beta-oxidation cycle in peroxisomes are normal in patients with X-linked adrenoleukodystrophy and that a specific defect of lignoceroyl-CoA synthetase is responsible for the accumulation of very long chain fatty acids in these patients.
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PMID:Effects of sodium 2-[5-(4-chlorophenyl)pentyl]-oxirane-2-carboxylate (POCA) on fatty acid oxidation in fibroblasts from patients with peroxisomal diseases. 199 2

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

We describe neonatal onset of a lethal multiorgan deficiency of carnitine palmitoyltransferase II (CPT II) associated with dysmorphic features, cardiomyopathy, and cystic dysplasia of the brain and kidneys. Concentrations of long-chain acylcarnitines were evaluated in blood and multiple tissues, diffuse lipid accumulation was present at autopsy, and a profound deficiency of CPT II activity was evident in heart, liver, muscle, and kidney tissue. This disorder constitutes another recognizable malformation syndrome with a metabolic basis. Deficiency of CPT II should be included in the differential diagnosis of patients with cystic renal dysplasia, dysmorphism, central nervous system malformations, and early death, along with glutaric acidemia type II, Zellweger syndrome, and other disorders in which peroxisomal beta-oxidation is impaired. The clinicopathologic similarities among these disorders raise the possibility that a common biochemical mechanism, namely the disruption of beta-oxidation of fatty acids, is responsible for the abnormal organogenesis.
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PMID:Lethal neonatal deficiency of carnitine palmitoyltransferase II associated with dysgenesis of the brain and kidneys. 765 72

The relationship between peroxisomal and mitochondrial oxidation of the methyl branched fatty acids, phytanic acid and pristanic acid, was studied in normal and mutant human skin fibroblasts with established enzyme deficiencies. Tandem mass spectrometry was used for analysis of the acylcarnitine intermediates. In normal cells, 4,8-dimethylnonanoylcarnitine (C11:0) and 2,6-dimethylheptanoylcarnitine (C9:0) accumulated after incubation with either phytanic acid or pristanic acid. These intermediates were not observed when peroxisome-deficient cells from Zellweger patients were incubated with the same compounds, pointing to the involvement of peroxisomes in the formation of these acylcarnitine intermediates. Similar experiments with fibroblasts deficient in carnitine palmitoyltransferase I, carnitine-acylcarnitine translocase or carnitine palmitoyltransferase II revealed that mitochondrial carnitine palmitoyltransferase I is not required for the oxidation of phytanic acid or pristanic acid, whereas both carnitine-acylcarnitine translocase and carnitine palmitoyltransferase II are necessary. These studies demonstrate that both phytanic acid and pristanic acid are initially oxidized in peroxisomes to 4,8-dimethylnonanoyl-CoA, which is converted to the corresponding acylcarnitine (presumably by peroxisomal carnitine octanoyltransferase), and exported to the mitochondrion. After transport across the mitochondrial membrane and transfer of the acylgroup to coenzyme A, further oxidation to 2,6-dimethylheptanoyl-CoA occurs.
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PMID:Phytanic acid and pristanic acid are oxidized by sequential peroxisomal and mitochondrial reactions in cultured fibroblasts. 946 87

Recently, we reported that baicalein 5,6,7-trimethyl ether (BTM), a flavonoid, is capable of activating fatty acid beta-oxidation in X-linked adrenoleukodystrophy (X-ALD) fibroblasts (FEBS Lett. 2005; 579: 409-414). The objective of this study was to clarify whether BTM activates peroxisomal and/or mitochondrial fatty acid beta-oxidation. We first analysed the effect of BTM on fatty acid beta-oxidation in fibroblasts derived from healthy controls as well as patients with X-ALD, mitochondrial carnitine-acylcarnitine translocase (CACT) deficiency, and peroxisome biogenesis disorder, Zellweger syndrome. Lignoceric acid (C(24:0)) beta-oxidation in the fibroblasts was stimulated by treatment with BTM, except for Zellweger fibroblasts. In contrasts, palmitic acid (C(16:0)) beta-oxidation was increased (2.8-fold) only in CACT-deficient fibroblasts. In U87 glioblastoma cells, C(24:0) beta-oxidation was also activated by treatment with BTM but C(16:0) beta-oxidation was not. The C(16:0) beta-oxidation was, however, significantly increased in the presence of 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA), a carnitine palmitoyltransferase I inhibitor. These results indicate that BTM activates peroxisomal but not mitochondrial fatty acid beta-oxidation. In addition, we found that BTM did not upregulate the expression of ABCD2/ALDR, ABCD3/PMP70, ACOX1 and FATP4 genes but slightly increased ACSVL1 gene expression.
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PMID:Baicalein 5,6,7-trimethyl ether activates peroxisomal but not mitochondrial fatty acid beta-oxidation. 1847 Jun 30