Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Deficiency of carnitine palmitoyltransferase II (CPT II), was found to be the cause of the syndrome of muscle pain and myoglobinuria following strenuous exercise in an otherwise healthy young man. During fasting, serum creatine kinase remained low and ketogenesis was normal. The clearance of a fat emulsion and the activity of extrahepatic lipoprotein lipase was lowered, while the hepatic lipoprotein lipase was normal. A skeletal muscle biopsy did not show abnormal lipid storage. CPT II was deficient in skeletal muscle and leucocytes, while CPT I activity was normal and exhibited normal kinetic properties. CPT I has a higher affinity for palmitoylcarnitine than CPT II, and is more inhibited at increasing palmitoylcarnitine concentrations. In erythrocytes only CPT I is present.
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PMID:Carnitine palmitoyltransferase II deficiency with normal carnitine palmitoyltransferase I in skeletal muscle and leucocytes. 76 93

Metabolic responses occurring 24 h following the secondary haematogenous dissemination of influenza B virus during convalescence from infection were examined in the ferret as a possible model for epiphenomena which can occur following infection with influenza. Among the major changes found were a further rise in the mean fasting serum free fatty acid (FFA) level to three times the control mean value and a 50% drop in the mean serum triglyceride (TG) concentration after the intravascular administration of a single bolus of virus compared to levels found in uninfected or convalescent animals. In adipose tissue, hormone-sensitive and lipoprotein lipase activities were increased six and three-fold, respectively, over mean control values, probably accounting for the changes that were observed in serum lipid concentrations. In the liver, total carnitine palmitoyltransferase (CPT) activity was affected only slightly and the total lipid content of the liver remained unchanged. These findings indicate that 24 h after the intravascular dissemination of homologous virus in a single bolus during convalescence from influenza B infection, major distortions in the regulation of lipid metabolism occur in the ferret. Loss of the synchronous regulation of the two adipose tissue lipases is a significant consequence leading to the mobilization of a large amount of FFA during fasting from both adipose tissue and the circulating plasma TG stores.
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PMID:Acute alterations in the regulation of lipid metabolism after intravascular reexposure to a single bolus of homologous virus during influenza B infection in ferrets: possible model of epiphenomena associated with influenza. 184 59

Incubation of isolated cardiac myocytes with 500 microM-8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP) or 100 microM-forskolin for 2 1/2 h did not increase the heparin-induced release of lipoprotein lipase (LPL) into the medium. When LPL activity in cardiac myocytes was depleted by treatment of rats with cycloheximide (2 mg/kg; 2.5 h) and inclusion of the protein-synthesis inhibitor in the isolation solutions, incubation with CPT-cAMP or forskolin did not influence the rate of repletion of LPL activity in cells or the recovery of heparin-releasable LPL activity. Although the administration of cholera toxin (0.5 mg/kg; 16-17 h) to rats increased LPL activity in a low-speed supernatant fraction from heparin-perfused hearts, LPL activity was not increased in cardiac myocytes from cholera-toxin-treated rat hearts, and the heparin-induced release of LPL was unchanged. Incubation of cultured ventricular myocytes with 1 microgram of cholera toxin/ml or 500 microM-CPT-cAMP for 24 h did not increase cellular LPL activity or LPL released into the culture medium after a 40 min incubation with heparin. Therefore interventions that stimulate adenylate cyclase activity (forskolin, cholera toxin) or incubation with CPT-cAMP do not increase cellular LPL activity or promote the translocation of LPL to a heparin-releasable fraction in cardiac myocytes.
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PMID:Treatment of cardiac myocytes with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate, forskolin or cholera toxin does not stimulate cellular or heparin-releasable lipoprotein lipase activities. 216 39

Administration of pharmacologic amounts of L-carnitine was studied in the hypertriglyceridemic Zucker rat. When administered subcutaneously, doses from 250 to 2,000 mg/kg/d significantly decreased plasma triglycerides in obese rats over eight to 12 weeks, with no effect on plasma triglycerides in lean rats. Oral doses at the same high levels were not effective in decreasing plasma triglycerides. Triglyceride secretion rate was reduced from 367 micrograms/min to 168 micrograms/min in treated obese rats. Concurrently, liver lipid was increased twofold in obese treated rats, and the livers of these rats showed significant fatty infiltration. The mechanism of action of carnitine in decreasing plasma triglycerides appeared to be via decreased secretion of triglycerides by the liver of obese rats. There was no effect of L-carnitine in lean or obese rats on the following variables: carnitine palmitoyltransferase-A kinetics or malonyl CoA inhibition, mitochondrial or peroxisomal oxidative capacity, lipoprotein lipase in heart, muscle, and adipose, or fecal lipids. The effect of pharmacologic L-carnitine thus appears to be an inhibition of triglyceride synthesis and/or secretion by the liver.
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PMID:Pharmacologic action of L-carnitine on hypertriglyceridemia in obese Zucker rats. 371 17

The review examines the mechanisms regulating the activities of the two key enzymes determining rates of glucose and fatty acid oxidation, i.e., the pyruvate dehydrogenase (PDH) complex and the carnitine palmitoyltransferase (CPT) system. The review also evaluates the regulatory importance of gene expression in the control of tissue fuel selection within the context of substrate competition between glucose and fatty acids. It identifies a strong indirect input of nutrient-gene interactions in the control of pyruvate oxidation through the regulated provision of pyruvate as a substrate for PDH and as an inhibitor of PDH kinase. Nutrient-gene interactions are also identified in relation to the regulation of CPT I activity by malonyl-CoA (inhibitor) and by the provision of long-chain acyl-CoA (substrate/activator), the latter via the hydrolysis of plasma or tissue triacylglycerol (by lipoprotein lipase and hormone-sensitive lipase, respectively). We discuss how such regulation is reinforced by long-term modulation of PDH kinase-specific activity and CPT I maximal activity. We also explore the role of mechanisms operating at the levels of the PDH complex and the CPT system that act to promote and accelerate a switch in fuel utilization once a committed change in nutrient supply has been established. In particular, we discuss the regulatory influences exerted by altered sensitivities of PDH kinase to inhibition by pyruvate and CPT I to inhibition by malonyl-CoA, respectively.
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PMID:Interactive regulation of the pyruvate dehydrogenase complex and the carnitine palmitoyltransferase system. 829 90

The effects of conjugated linoleic acid (CLA) on body composition were investigated. ICR mice were fed a control diet containing 5.5% corn oil or a CLA-supplemented diet (5.0% corn oil plus 0.5% CLA). Mice fed CLA-supplemented diet exhibited 57% and 60% lower body fat and 5% and 14% increased lean body mass relative to controls (P < 0.05). Total carnitine palmitoyltransferase activity was increased by dietary CLA supplementation in both fat pad and skeletal muscle; the differences were significant for fat pad of fed mice and skeletal muscle of fasted mice. In cultured 3T3-L1 adipocytes CLA treatment (1 x 10(-4)M) significantly reduced heparin-releasable lipoprotein lipase activity (-66%) and the intracellular concentrations of triacylglyceride (-8%) and glycerol (-15%), but significantly increased free glycerol in the culture medium (+22%) compared to control (P < 0.05). The effects of CLA on body composition appear to be due in part to reduced fat deposition and increased lipolysis in adipocytes, possibly coupled with enhanced fatty acid oxidation in both muscle cells and adipocytes.
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PMID:Effect of conjugated linoleic acid on body composition in mice. 927 Sep 77

The percentage of slow-twitch (ST) fibers in a person's skeletal muscle, e.g. muscle fiber composition (ST-%), may have a significant impact on physical activity, fitness level, serum high density lipoprotein cholesterol (HDL-C) concentration, and ultimately, on the risk of coronary heart disease (CHD). We studied the effect of a 12 month home-based exercise training program on skeletal muscle metabolic activity, serum lipids, and hormones in 12 healthy middle-aged men (sedentary men) with a low level of fitness and leisure-time physical activity (LTPA). Their parameters and changes in them were compared with 12 men of the same age with defined CHD and with two groups (15 each) of physically active men, who had either a high ST-% (high-ST-men) or a low ST-% (low-ST-men). In the sedentary men, CHD-patients and low-ST-men, the mean ST-% (42, 44, and 49%, respectively) was similar but was significantly higher in the high-ST-men (73%). The sedentary men whose LTPA mean was 34 and 19% of the mean of low-ST-men (mean of 2137 kcal/week) and high-ST-men (mean of 3845 kcal/week), respectively, increased their LTPA from a mean of 728-1526 kcal/week (P < 0.01). After training, we found an increase in serum HDL-C by 21%, (P < 0.01) and apo A-I by 36% (P < 0.01), and a decrease in serum LDL-C by 8%. The cholesterol/HDL-C ratio decreased by 17(% (P < 0.01) and the LDL-C/HDL-C ratio decreased by 22% (P < 0.01). Skeletal muscle lipoprotein lipase (LPL) activity increased by 65% (P < 0.001). Moreover, the increase in LPL as well as in HDL-C concentration tended to be more pronounced the higher the level was before training. The oxidative enzyme activity of alpha-ketoglutarate dehydrogenase (KGDH) in skeletal muscle and the activity of carnitine palmitoyltransferase (CPT) in lipid metabolism increased, whereas glycolytic phosphofructokinase (PFK) did not change but the PFK to CPT ratio decreased, which was reflected as a decrease of lactate accumulation during exercise. Increase in CPT activity correlated significantly (r(s) = 0.81, P < 0.01) with the increase in HDL-C concentration. In all men (n = 54), the CPT activity correlated negatively with serum triglyceride concentration (r(s) = -0.34, P < 0.05) but positively with serum HDL-C concentration and ST-% (r(s) = 0.34, P < 0.05 and r(s) = 0.47, P < 0.01, respectively). In all healthy men, (n = 42) LTPA correlated with both Vo2max, and ST-% (r(s) = 0.76, P < 0.001 and r(s) = 0.54, P < 0.001, respectively) and with serum HDL-C and apo A-I concentrations (r(s) = 0.35, P < 0.05 and r(s) = 0.54, P < 0.001, respectively). Serum sex hormones did not show significant associations with serum lipids, but in sedentary men, serum total and free testosterone as well as the ratio of free testosterone to free estradiol decreased significantly after training. These findings confirm the pronounced effects of a home-based exercise training program on CHD risk factors and they underline the importance of considering skeletal muscle properties when studying serum lipids and lipoproteins and their modifications in the field of health-related fitness and physical activity.
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PMID:Significance of skeletal muscle properties on fitness, long-term physical training and serum lipids. 1003 Mar 88

As part of an ongoing search for susceptibility genes in obese families, we performed linkage analyses in 101 French families between qualitative and quantitative traits related to morbid obesity and polymorphisms located in or near 15 candidate genes whose products are involved in body weight regulation. These included cholecystokinin A and B receptors (CCK-AR and CCK-BR), glucagon-like peptide 1 receptor (GLP-1R), the LIM/homeodomain islet-1 gene (Isl-1), the caudal-type homeodomain 3 (CDX-3), the uncoupling protein 1 (UCP-1), the beta3-adrenoceptor (beta3-AR), the fatty acid-binding protein 2 (FABP-2), the hormone-sensitive lipase (HSL), the lipoprotein lipase (LPL), the apoprotein-C2 (apo-C2), the insulin receptor substrate-1 (IRS-1), the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and the liver carnitine palmitoyltransferase-1 (CPT-1). Phenotypes related to obesity such as BMI, adult life body weight gain, fasting leptin, insulin, fasting glycerol, and free fatty acids were used for nonparametric sib-pair analyses. A weak indication for linkage was obtained between the Isl-1 locus and obesity status defined by a z score over one SD of BMI (n = 226 sib pairs, pi = 0.54 +/- 0.02, P = 0.03). Moreover, a suggestive indication for linkage was found between the Isl-1 locus and BMI and leptin values (P = 0.001 and 0.0003, respectively) and leptin adjusted for BMI (P = 0.0001). Multipoint analyses for leptin trait with Isl-1 and two flanking markers (D5S418 and D5S407) showed that the logarithm of odds (LOD) score is 1.73, coinciding with the Isl-1 locus. Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity. Whether an obesity susceptibility gene (Isl-1 itself or another nearby gene) lies on chromosome 5q should be determined by further analyses.
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PMID:A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q. 1033 20

Plasma TGs, FFAs, and muscle TG are oxidizable lipid fuel sources for skeletal muscle metabolism during prolonged exercise. Plasma FFAs are a major fuel oxidized by skeletal muscle, and their rate of use by muscle depends on several factors, including plasma FFA availability, transport from plasma to the mitochondria, and intracellular metabolism. Mobilization of FFAs from adipose tissue is the first committed step in FFA metabolism, and it depends on the rate of adipose tissue lipolysis. Adipose tissue lipolysis increases with exercise duration and exercise intensity up to intensities of approximately 60% to 65%. Evidence suggests that FFAs are transported from plasma to the mitochondria by FFA transporter proteins that include the plasma membrane and cytosolic FABPPM and FABPC. Plasma FFA use can also be regulated at the mitochondrial transport step by changing the activity of carnitine palmitoyltransferase (CPT-1). Although results from biopsy and tracer studies indicate that muscle TG contribute to skeletal muscle oxidative metabolism during exercise, their exact contribution is difficult to ascertain. Evidence shows that muscle TG use depends on exercise intensity, duration, and mode. The contribution of plasma TG to skeletal muscle metabolism is small. The rate of use of plasma TG is dependent on lipoprotein lipase activity, which is correlated with the oxidative capacity of the muscle fibers. Dietary manipulations can modulate substrate use during exercise and can potentially affect exercise performance. High carbohydrate availability before exercise is associated with an increase in blood glucose and plasma insulin concentrations, which can ultimately decrease the rate of adipose tissue lipolysis and the availability of plasma FFAs. Increased glucose flux has also been shown to decrease lipid oxidation by directly inhibiting the transport of FFAs across the mitochondrial membranes. High lipid availability can be changed by short-term or long-term exposure to high-fat diets. Because carbohydrate reserves are diminished with exposure to high-fat diets, improvements in exercise performance have been difficult to measure under these conditions.
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PMID:Role of fats in exercise. Types and quality. 1041 Aug 36

The peroxisome proliferator-activated receptors (PPARs) [alpha, delta (beta) and gamma] form a subfamily of the nuclear receptor gene family. All PPARs are, albeit to different extents, activated by fatty acids and derivatives; PPAR-alpha binds the hypolipidemic fibrates whereas antidiabetic glitazones are ligands for PPAR-gamma. PPAR-alpha activation mediates pleiotropic effects such as stimulation of lipid oxidation, alteration in lipoprotein metabolism and inhibition of vascular inflammation. PPAR-alpha activators increase hepatic uptake and the esterification of free fatty acids by stimulating the fatty acid transport protein and acyl-CoA synthetase expression. In skeletal muscle and heart, PPAR-alpha increases mitochondrial free fatty acid uptake and the resulting free fatty acid oxidation through stimulating the muscle-type carnitine palmitoyltransferase-I. The effect of fibrates on the metabolism of triglyceride-rich lipoproteins is due to a PPAR-alpha dependent stimulation of lipoprotein lipase and an inhibition of apolipoprotein C-III expressions, whereas the increase in plasma HDL cholesterol depends on an overexpression of apolipoprotein A-I and apolipoprotein A-II. PPARs are also expressed in atherosclerotic lesions. PPAR-alpha is present in endothelial and smooth muscle cells, monocytes and monocyte-derived macrophages. It inhibits inducible nitric oxide synthase in macrophages and prevents the IL-1-induced expression of IL-6 and cyclooxygenase-2, as well as thrombin-induced endothelin-1 expression, as a result of a negative transcriptional regulation of the nuclear factor-kappa B and activator protein-1 signalling pathways. PPAR activation also induces apoptosis in human monocyte-derived macrophages most likely through inhibition of nuclear factor-kappa B activity. Therefore, the pleiotropic effects of PPAR-alpha activators on the plasma lipid profile and vascular wall inflammation certainly participate in the inhibition of atherosclerosis development observed in angiographically documented intervention trials with fibrates.
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PMID:Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. 1043 61


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