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

A 15-year-old girl with a large accumulation of lipid in the muscle fibers, was suffering from systemic carnitine deficiency. She died in acidosis. The blood carnitine level was normal. At necropsy, carnitine levels were low in skeletal muscles and heart, whilst a normal level was found in the liver. Carnitine palmitoyltransferase II and palmitoyl-CoA synthetase activities were increased, whereas carnitine acetyltransferase, glycerol-3-phosphate dehydrogenase (FAD) and succinate dehydrogenase were decreased. Investigation of blood and skeletal muscle of the family members revealed marked abnormalities in a 7-year old sister who had only minor neurological symptoms. Histochemical investigation revealed abnormal accumulations of lipid between the myofibrils. Carnitine was decreased in her skeletal muscle and blood. Muscular carnitine palmitoyltransferase II and palmitoyl-CoA synthetase were again increased in activity while glycerol-3-phosphate dehydrogenase (FAD) was decreased. The activities of succinate dehydrogenase, carnitine palmitoyltransferase I and glycerol-3-phosphate dehydrogenase (NAD+) were normal. The unexpected normal carnitine level in blood and liver of the deceased patient was attributed to muscle wasting, which was confirmed by the very high blood level of creatine phosphokinase. This fatal case indicates that the fasting condition must be avoided in persons with carnitine deficiency. In crises, glucose supply is necessary since gluconeogenesis may be blocked.
 ...
PMID:Familial carnitine deficiency. A fatal case and subclinical state in a sister. 15 48

1-Carnitine was administered to fed rats and the changes in plasma beta-hydroxybutrate concentration and liver acid-insoluble acylcarnitine content were assessed. One hour following injection of carnitine in doses greater than 1 mumol/100 g of body weight there was a dose-dependent increase in liver acid-insoluble acylcarnitine content to levels comparable to those seen in fasting. These increased levels were maintained for a least 2 h following injection. During the period following carnitine administration there was no increase in ketogenesis as evidenced by plasma beta-hydroxybutyrate concentrations. Since acid-insoluble acylcarnitines represent the product of carnitine palmitoyltransferase A, the results are interpreted as contradictory to the theory that this enzyme is rate-limiting and regulatory for ketogenesis.
 ...
PMID:Disassociation between acidinsoluble acylcarnitines and ketogenesis following carnitine administration in vivo. 67 Jan 95

The subcellular distribution of carnitine acetyl-, octanoyl-, and palmitoyl- transferase in the livers of normal and clofibrate-treated male rats was studied with isopycnic sucrose density gradient fractionation. In normal liver 48% of total carnitine acetyltransferase activity was peroxisomal, 36% of the activity located in mitochondria and 16% in a membranous fraction containing microsomes. Carnitine octanoyltransferase and carnitine palmitoyltransferase were confined almost totally (77--81%) to mitochondria in normal liver. Clofibrate treatment increased the total activity of carnitine acetyltransferase over 30 times, whereas the total activities of the other two transferases were increased only 5-fold. From the three different subcellular carnitine acetyltransferases the mitochondrial one was most responsive to clofibrate treatment, i.e. the rise in mitochondrial activity was over 70-fold as contrasted to the 6- and 14-fold rises in peroxisomal and microsomal activities, respectively. After treatment mitochondria contained 79% of total activity. It is concluded that the clofibrate-induced increase of carnitine acetyltransferase activity is not due to the peroxisomal proliferation that occurs during clofibrate treatment. The rise in peroxisomal activity contributed only 8% to the total increase. After clofibrate treatment the greatest part of carnitine octanoyl- and palmitoyltransferase activities were located in mitochondria but a considerable amount of both activities was found also in the soluble fraction of liver.
 ...
PMID:Effect of clofibrate treatment on carnitine acyltransferases in different subcellular fractions of rat liver. 127 75

The regulation of heart carnitine palmitoyltransferase was studied during the transition to the fasting state. Using decanoyl-CoA or palmitoyl-CoA as substrates, we found no differences in carnitine palmitoyltransferase activity or in its sensitivity to inhibition by malonyl-CoA between fed and fasted states. No cooperativity was seen with either substrate, and the malonyl-CoA-induced shift to sigmoid kinetics normally observed with liver mitochondria was not obvious with heart mitochondria. Analysis of malonyl-CoA inhibition data revealed that mitochondria from rat heart exhibited incomplete maximum inhibition of carnitine palmitoyltransferase (partial inhibition). Homogenization of intact liver mitochondria resulted in a similar pattern of incomplete inhibition and suggested that the malonyl-CoA-insensitive carnitine palmitoyltransferase of the inner membrane was also being assayed. Carnitine palmitoyltransferase in mitochondrial outer membranes, isolated from the heart, proved to be extremely sensitive to malonyl-CoA inhibition and had maximum inhibition values of 90-100% with either decanoyl-CoA or palmitoyl-CoA as substrates, but fasting had no effect. Fasting produced no change in the Ki for malonyl-CoA (0.10 +/- 0.04 and 0.14 +/- 0.02 microM for the fed and fasted groups, respectively). Acyl-CoA chain length specificity was C10 greater than C16 greater than C14 greater than C12 greater than C18 = C8 for carnitine palmitoyltransferase in heart mitochondrial outer membranes. It is concluded that the regulation of carnitine palmitoyltransferase of heart mitochondrial outer membranes differs from regulation of the liver enzyme in three characteristics--the heart enzyme (a) has greater sensitivity to malonyl-CoA inhibition, (b) is resistant to the effects of fasting and (c) has somewhat different acyl-CoA substrate specificity.
 ...
PMID:Myocardial carnitine palmitoyltransferase of the mitochondrial outer membrane is not altered by fasting. 139 Aug 73

The heart utilizes fatty acids as a substrate in preference to glucose for the production of energy. The rate of fatty acid uptake and oxidation by heart muscle is controlled by the availability of exogenous fatty acids, the rate of acyl translocation across the mitochondrial membrane and the rate of acetyl-CoA oxidation by the citric acid cycle. Carnitine acyl-CoA transferase appears to have an important function in coupling the fatty acid activation and acyl transfer to the oxidative phosphorylation. Activated fatty acids are also utilized for the synthesis of triglycerides and membrane phospholipids in the myocardium. The inhibition of long chain acyl-carnitine transferase I reduces the oxidation of fatty acids and promotes the synthesis of lipids in the myocardium. Accumulation of fatty acids and their metabolites such as long chain acyl-CoA and long chain acyl-carnitine has been associated with cardiac dysfunction and cell damage in both ischemic and diabetic hearts. Alterations in the composition of membrane phospholipids are also considered to change the activities of various membrane bound enzymes and subsequently heart function under different pathophysiological conditions. Chronic diabetes was found to be associated with increased plasma lipids, subcellular defects and cardiac dysfunction. Lowering the plasma lipids or reducing the oxidation of fatty acids by agents such as etomoxir, an inhibitor of palmitoylcarnitine transferase I was found to promote glucose utilization and remodel the subcellular membranous organelles in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Paradoxical role of lipid metabolism in heart function and dysfunction. 148 Jan 51

The formation of palmitoylcarnitine is catalyzed by carnitine palmitoyl-transferase (CPT-I) and this catalysis is the first committed step in beta-oxidation. The malonyl-CoA-inhibited isoform appears to be distinct from latent (CPT-II) activity, which is localized to the matrix side of the mitochondrial inner membrane. Sarcoplasmic reticulum from canine cardiac muscle was fractionated on a discontinuous sucrose density gradient into three major bands, all of which contained Ca(2+)-ATPase activity. Only the fraction that banded at a concentration of 38% surcrose was slightly contaminated by mitochondria. Peroxisomal uricase was low or absent in fractionated SR. All sarcoplasmic reticulum fractions contained malonyl-CoA-sensitive medium- (COT) and long-chain (CPT) carnitine acyltransferase activities. CPT activity decreased in sarcoplasmic reticulum when Triton X-100 was present. Carnitine acyltransferase activities were inactivated by preincubating the sarcoplasmic reticulum with the sulfhydryl reagent, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). In contrast, mitochondrial CPT-II activity was stable in the presence of DTNB and activated by Triton X-100. Western blots of mitochondria and sarcoplasmic reticulum fractions showed that the mitochondrial fractions reacted with antibody to mitochondrial CPT-II but not with SR protein when both were added at comparable specific activities. The data suggest that cardiac SR contains a unique malonyl-CoA-sensitive isoform of CPT, and that synthesis of acylcarnitine may occur in the microenvironment of Ca2+ transport, where the extent of production of acylcarnitine is controlled by cardiac acetyl-CoA carboxylase activity.
 ...
PMID:Evidence for malonyl-CoA-sensitive carnitine acyl-CoA transferase activity in sarcoplasmic reticulum of canine heart. 162 48

Regulation of in vitro palmitate metabolism by carnitine and propionate was investigated in liver obtained by biopsy from fasted nonlactating cows and from cows during early lactation. Liver slices from nonlactating cows during a 7-d fast esterified less palmitate than those from the same cows before fasting. Carnitine added in vitro increased hepatic oxidation and decreased esterification of palmitate in fed cows, but effects of carnitine were less during fasting. Propionate added in vitro decreased oxidation of palmitate; the effect was greater during fasting. In liver slices from cows during early lactation, carnitine increased oxidation and total utilization of palmitate and decreased palmitate esterification. Addition of tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase I, prevented the carnitine-induced changes in palmitate metabolism. Substantial carnitine-independent oxidation of palmitate was observed in the presence of tetradecylglycidic acid. Tetradecylglycidic acid decreased esterification of palmitate to triglycerides but increased esterification to diglycerides. Effects of tetradecylglycidic acid and either propionate or pyruvate on palmitate oxidation were additive, indicating that propionate and pyruvate affect palmitate oxidation at sites other than carnitine palmitoyltransferase I. No interactions were detected between carnitine and propionate, but both compounds were potent regulators of palmitate metabolism in liver slices from cows during early lactation.
 ...
PMID:Regulation of in vitro metabolism of palmitate by carnitine and propionate in liver from dairy cows. 177 55

Carnitine acyltransferase activities in the hearts of normal and dystrophic, sedentary and swim exercised hamsters were studied, in order to analyze the relationship between carnitine metabolism and exercise in cardiomyopathy. After 12 weeks, the mean specific activities of cardiac carnitine acetyltransferase (CAT), carnitine octanoyltransferase (COT) and carnitine palmitoyltransferase (CPT) were significantly higher in the dystrophic sedentary group, relative to the normal sedentary group (p less than 0.05). There was no significant effect of exercise on the mean specific activity of the carnitine acyltransferases, compared to the dystrophic or normal sedentary controls. Thus, the improvements in cardiac histopathology due to exercise noted previously are not associated with altered carnitine acyltransferase activity.
 ...
PMID:Cardiac carnitine acyltransferase activities in exercised normal and dystrophic hamsters. 178 40

Carnitine acyltransferase activities were studied in normal human skeletal muscle and in muscle of three patients with carnitine palmitoyltransferase deficiency. Carnitine acetyltransferase (CAT), carnitine octanoyltransferase (COT), and carnitine palmitoyltransferase (CPT) were differentiated (i) by the use of the substrates acetyl-CoA, octanoyl-CoA, lauroyl-CoA, and palmitoyl-CoA, (ii) by the inhibitors malonyl-CoA, chlorpromazine, and dithio-bis-nitrobenzoic acid (DTNB), and (iii) by the solubilities of the carnitine acyltransferase activities after centrifugation at 48,000 g for 30 min. The results are consistent with the notion of three different carnitine acyltransferases in human skeletal muscle: a membrane-bound malonyl-CoA-sensitive CPT, a soluble malonyl-CoA-insensitive CAT, and a malonyl-CoA-sensitive COT that is not attached to the mitochondrial membrane. The different solubilities of the carnitine acyltransferases allow a clear differentiation of CPT from CAT and COT in homogenates of previously frozen muscle biopsies whereas a separate determination of CAT and COT is only partially possible. In patients with CPT deficiency total CPT activity was within the normal range but was abnormally inhibited by malonyl-CoA and chlorpromazine. Activities of carnitine acyltransferases with the substrates acetyl-CoA and octanoyl-CoA were normal indicating that the biochemical defect in CPT deficiency is confined to CPT without compensatory changes of CAT and COT.
 ...
PMID:Carnitine acyltransferases in normal human skeletal muscle and in muscle of patients with carnitine palmitoyltransferase deficiency. 182 3

Carnitine palmitoyltransferase located in the erythrocyte plasma membrane is sensitive to inhibition by malonyl-CoA and 2-bromopalmitoyl-CoA plus carnitine. Although this inhibition and other properties suggest similarities to the intracellular enzymes in other tissues, no cross-reaction was observed with antisera to the peroxisomal or to the mitochondrial inner-membrane enzyme. The activity was solubilized by and was stable in Triton X-100, which destroys the enzymes found in microsomes and in the mitochondrial outer membrane. The substrate specificity is broader than for the intracellular enzymes, the activities with stearoyl-CoA (114%) and arachidonoyl-CoA (97%) being equal to that with palmitoyl-CoA, and the activities with linoleoyl-CoA (44%) and erucoyl-CoA (46%) about half that with palmitoyl-CoA. The function of this carnitine palmitoyltransferase is probably to buffer the acyl-CoA present in the erythrocyte for turnover of the fatty acyl groups of the membrane lipids.
 ...
PMID:Carnitine palmitoyltransferase in human erythrocyte membrane. Properties and malonyl-CoA sensitivity. 203 46


1 2 3 4 5 6 7 8 9 10 Next >>