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)

Okadaic acid parallely increased carnitine [corrected] palmitoyltransferase I activity and the rate of palmitate oxidation in isolated rat hepatocytes. Nevertheless, okadaic acid had no significant effect on the rate of octanoate oxidation. Maximal effects of okadaic acid were similar and non-additive to those of dibutyryl-cAMP, forskolin and glucagon. Results indicate that carnitine palmitoyltransferase I activity may be controlled by a mechanism of phosphorylation/dephosphorylation.
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PMID:Okadaic acid stimulates carnitine palmitoyltransferase I activity and palmitate oxidation in isolated rat hepatocytes. 193 36

When added to the hepatocyte incubation medium, vanadate increased the rate of fatty acid synthesis de novo as well as the activity of acetyl-CoA carboxylase, whereas it had no effect on the activity of fatty acid synthase. On the other hand, and despite elevating the intracellular levels of malonyl-CoA, vanadate diverted exogenous fatty acids into the oxidation pathway at the expense of the esterification route. This was concomitant to an increase in carnitine palmitoyltransferase I activity. All these effects were not significantly different between periportal and perivenous hepatocytes and were also evident in cells incubated in Ca2(+)-free medium. Nevertheless, Ca2+ ions enhanced carnitine palmitoyltransferase I activity in isolated liver mitochondria. In addition, the effects of vanadate on acetyl-CoA carboxylase and carnitine palmitoyltransferase I were only evident in a permeabilized-cell assay, disappearing upon cell disruption and isolation of the corresponding cell subfraction for enzyme assay. Results show that vanadate exerts specific insulin-like and non-insulin-like effects on hepatic fatty acid metabolism, and suggest that the intracellular concentration of malonyl-CoA is not the only factor responsible for the regulation of the fatty-acid-oxidative process in the liver.
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PMID:Simultaneous stimulation of fatty acid synthesis and oxidation in rat hepatocytes by vanadate. 197 36

Substrate saturation plots of carnitine palmitoyltransferase I activity from isolated rat liver mitochondria vs. palmitoyl-CoA concentration in the presence of bovine serum albumin have been reported to yield sigmoidal kinetics. Under identical assay conditions we have confirmed these observations as reflected by nonlinear Lineweaver-Burke plots (1/vi vs. 1/[S]) an average Hill coefficient of napp. = 1.98 +/- 0.09 (Mean +/- S.E. from four separate experiments). For these determinations the enzyme activity was plotted against the total [palmitoyl-CoA] in the presence of 0.13% bovine serum albumin. Utilizing the total [palmitoyl-CoA] to determine the kinetic properties of carnitine palmitoyltransferase I would be valid only if the relationship between total and free [palmitoyl-CoA] was linear, which is not the case as we have previously shown. When carnitine palmitoyltransferase I substrate saturation kinetics were reanalyzed using the previously determined free [palmitoyl-CoA]'s, the plots revealed a shift to standard hyperbolic kinetics. This observation was confirmed by an average Hill coefficient of napp. = 1.04 +/- 0.10 (Mean +/- S.E.) and linear Lineweaver-Burke plots. The double-reciprocal plots from these analyses yielded an average S0.5 of 2.55 +/- 0.82 microM (Mean +/- S.E.) palmitoyl-CoA and Vmax of 19.69 +/- 5.48 nmol/min per mg protein. These studies clearly demonstrate the importance of defining the free [palmitoyl-CoA] when analyzing the kinetics of carnitine palmitoyltransferase I in the presence of bovine serum albumin.
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PMID:The effect of palmitoyl-CoA binding to albumin on the apparent kinetic behavior of carnitine palmitoyltransferase I. 198 92

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

Rats were fed for 35 days a high-fat diet containing either 36% of total calories as ethanol (ethanol group) or an isocaloric amount of carbohydrate (control group). Then, mitochondria were isolated from the periportal and the perivenous zone of the liver in order to study the acinar heterogeneity of the effects of prolonged ethanol administration upon the properties of carnitine palmitoyltransferase I (CPT-I) and its membrane environment. Chronic ethanol ingestion selectively decreased CPT-I activity in periportal hepatocytes but equally increased enzyme sensitivity to malonyl-CoA and enzyme energy of activation in the two zones of the liver. In control animals, mitochondrial membrane showed higher fluidity and lower degree of saturation of phospholipid fatty acyl moieties in periportal than in perivenous hepatocytes. Prolonged ethanol feeding (i) decreased mitochondrial membrane fluidity; (ii) increased the proportion of palmitic acid and decreased that of arachidonic acid in mitochondrial phosphatidylcholine and phosphatidylethanolamine, whereas it drastically reduced the content of linoleic acid and concomitantly increased that of saturated and monoenoic fatty acids in cardiolipin; (iii) suppressed the disordering effects of the addition of ethanol to mitochondrial suspensions. All these ethanol-induced alterations of membrane fluidity and fatty acyl composition were not significantly different between periportal and perivenous mitochondria. In conclusion, chronic ethanol feeding changes the activity of CPT-I in a zone-selective manner but modifies both the regulatory properties of the enzyme and the properties of its lipid environment in a non-zone-selective manner. Hence factors in addition to the properties of the mitochondrial membrane seem to be involved in the ethanol-induced alterations of the CPT-I enzyme.
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PMID:Properties of the mitochondrial membrane and carnitine palmitoyltransferase in the periportal and the perivenous zone of the liver. Effects of chronic ethanol feeding. 203 48

Previous work in this laboratory has shown that muscle malonyl-CoA, the inhibitor of carnitine palmitoyltransferase I (CPT I), decreased during exercise. Hepatic malonyl-CoA content decreases when glucose availability decreases such as during fasting or when the glucagon-to-insulin ratio increases such as during prolonged exercise or in response to insulin deficiency. To investigate the effect of glucose infusion on muscle malonyl-CoA during exercise, male rats were anesthetized (pentobarbital via venous catheters) at rest or after running (21 m/min, 15% grade) for 30 or 60 min. During exercise rats were infused with either glucose (0.625 g/ml) or saline at a rate of 1.5 ml/h. Gastrocnemius muscles and liver samples were frozen at liquid nitrogen temperature. Muscle malonyl-CoA decreased from 1.24 +/- 0.06 to 0.69 +/- 0.05 nmol/g with glucose infusion and to 0.43 +/- 0.04 nmol/g with saline infusion during 60 min of exercise. In the liver, glucose infusion prevented the drop in malonyl-CoA. This indicates that glucose infusion attenuates the progressive decline in muscle malonyl-CoA and prevents the decline in liver malonyl-CoA during prolonged exercise.
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PMID:Effect of glucose infusion on muscle malonyl-CoA during exercise. 205 26

1. The effect of changes in fatty acid beta-oxidation activity on triglyceride and cholesteryl ester synthesis were studied in cultured smooth muscle cells (SMC) and in a macrophage cell line IC-21 in the presence of oleic acid (100 microM). 2. Etomoxir, an inhibitor of carnitine palmitoyltransferase I, stimulated the incorporation of [2-3H]glycerol into triglycerides in SMC and in macrophages 6.2- and 8.2-fold, respectively, and the incorporation of [4-14C]cholesterol into cholesteryl esters in macrophages 3.5-fold. 3. L-Carnitine, a cofactor of fatty acid beta-oxidation, decreased the incorporation of [2-3H]glycerol into triglycerides in smooth muscle cells by 69% and the incorporation of [4-14C]cholesterol into cholesteryl esters by 52%. L-Carnitine had no effect on the macrophages.
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PMID:Balance between fatty acid degradation and lipid accumulation in cultured smooth muscle cells and IC-21 macrophages exposed to oleic acid. 206 Feb 77

The role of body fat in the control of food intake is considered from the point of view that the oxidation of metabolic fuels generates a signal that governs feeding behavior. According to this perspective, the storage and mobilization of fat affect food intake indirectly by altering fuel oxidation. Hyperphagia during the development of obesity is thus treated as an appropriate response to a primary metabolic defect that causes fuels to be stored rather than oxidized. Evidence is presented that changes in insulin level and the activity of carnitine palmitoyltransferase I modulate feeding by altering the partitioning of fatty acids. The possibility that dietary interactions, acting through these mechanisms, may cause overeating of high-fat diets is discussed. It is proposed that the signal for feeding originates in the liver when both fatty acids and glucose are unavailable for oxidation.
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PMID:Body fat and the metabolic control of food intake. 208 16

Carnitine palmitoyltransferase II of rat heart mitochondria was purified to homogeneity by a rapid method exploiting the hydrophobic nature of the protein. The method involves solubilization of mitochondrial membrane proteins by detergents and subsequent fractionation by hydrophobic affinity chromatography. Sepharose, cross-linked via a primary amino group of 1,omega-diaminoalkane, 4-aminobutyric acid, 6-aminocaproic acid, or 6-aminohexanol, was found to reversibly bind carnitine palmitoyltransferase under nondenaturing conditions. A homologous series of n-alkyl-agarose resins with n = 2 to 8 and phenyl-Sepharose were also found to reversibly bind the enzyme. Alkyl-Superose, phenyl-Superose, and Superose 12 chromatographies were also very useful in fractionating the enzyme. Successive chromatography on three or four hydrophobic columns yielded a highly pure enzyme preparation. The purified preparation appeared as one major protein band on polyacrylamide electrophoresis gels in the presence of sodium dodecyl sulfate (M(r) 68,000). The isolated enzyme had significant activity (sp act = 15.0 mumol/min/mg protein when 80 microM palmitoyl-CoA and 20 mM carnitine were used as substrates). Antibodies against this protein recognized (in immunoblots) one major protein band in crude preparations of rat heart mitochondria (M(r) 68,000), indistinguishable from purified carnitine palmitoyltransferase II. L-Palmitoylcarnitine (0.1 mM) and coenzyme A (0.1 mM), products of the enzyme-catalyzed reaction, inhibited carnitine palmitoyltransferase activity 66 and 71%, respectively. D-Palmitoylcarnitine (0.1 mM), however, did not inhibit the activity. Malonyl-CoA, a specific inhibitor of membrane-bound carnitine palmitoyltransferase I, did not show significant inhibition.
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PMID:Purification of carnitine palmitoyltransferase from heart mitochondria by hydrophobic affinity chromatography. 213 38

Malonyl-CoA is a potent inhibitor of carnitine palmitoyltransferase I (CPT-I), the rate-limiting enzyme for fatty acid oxidation in mitochondria from liver of fed rats. Malonyl-CoA has also been demonstrated to inhibit skeletal muscle CPT-I. This study was designed to determine the rate of decline in malonyl-CoA in muscle during the course of a prolonged exercise bout. Adult male rats were anesthetized (pentobarbital sodium, intravenously) at rest or after running for 5, 10, 20, 30, 60, or 120 min on a treadmill (21 m/min, 15% grade). Malonyl-CoA was then quantitated in the soleus (type I fibers) and in the superficial white (type IIB) and deep red (type IIA) regions of the quadriceps. Malonyl-CoA decreased in red quadriceps from 2.8 +/- 0.2 to 1.4 +/- 0.2 pmol/mg after 5 min and to 0.9 +/- 0.1 pmol/mg after 20 min of exercise. The concentration of malonyl-CoA remained at this level for the duration of the exercise bout (120 min). In white quadriceps, resting values of malonyl-CoA were lower than in red quadriceps, and a significant decline was not observed until 30 min of exercise. A significant decrease in the soleus was observed after 20 min of exercise. This decline in muscle malonyl-CoA may be an important signal for allowing increased fatty acid oxidation during long-term exercise.
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PMID:Time course of exercise-induced decline in malonyl-CoA in different muscle types. 216 37


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