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)

To study possible factors in the pathogenesis of the ethanol-induced fatty liver, we investigated the effect of chronic ethanol consumption on the metabolism of fatty acids by isolated hepatic mitochondria. Chronic ethanol consumption resulted in decreased fatty acid oxidation, as evidenced by a reduction in oxygen uptake and CO2 production associated with the oxidation of fatty acids. The State 3 rate of oxygen uptake was depressed to a greater extent than the State 4 or the uncoupler-stimulated rate; the respiratory control ratio was also decreased. Therefore, one site of action of chronic ethanol feeding is on oxidative phosphorylation. The reduction in fatty acid oxidation, in general, is not due to an effect on the activation or translocation of fatty acids into the mitochondria. There was no effect by ethanol feeding on the activity of palmitoyl coenzyme A synthetase, whereas carnitine palmitoyltransferase activity was increased. The use of an artificial system (formazan production) to study beta oxidation in the absence of the electron transport chain is described. In the presence of fluorocitrate, which inhibits citric acid cycle activity, ketogenesis and formazan production were increased by chronic ethanol consumption. Thus beta oxidation to the level of acetyl-CoA is not impaired by chronic ethanol consumption. Total oxidation of fatty acids to CO2 is depressed by chronic ethanol intoxication because of effects on oxidative phosphorylation or the citric acid cycle (or both). Neither nutritional deficiency, cofactor depletion, nor the presence of ethanol in vitro explains these effects. Several of the effects of chronic ethanol consumption on fatty acid oxidation are mimicked by acetaldehyde and acetate, products of ethanol oxidation. Chronic ethanol consumption leads to persistent impairment of mitochondrial oxidation of fatty acids to CO2. However, oxidation of fatty acids to acetyl-CoA is not decreased by chronic ethanol consumption.
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PMID:Effect of chronic ethanol ingestion on fatty acid oxidation by hepatic mitochondria. 117 Oct 98

Isolated rat atria in hypoxia released lactate into the bathing medium and underwent a decline of the contraction frequency which, in some cases led to a complete cessation of the pacemaker activity. A pronounced fall in the peak developed tension and a rise in the resting tension also appeared. The atria from 24 h fasted rats, which oxidize faster their reserve lipids than those from fed rats, exhibited greater functional disturbances during hypoxia, a lower lactate output and a smaller recovery of peak tension upon reoxygenation. Methyl palmoxirate, which is a selective inhibitor of carnitine palmitoyltransferase I, attenuated the decline of the beating rate and the rise of the resting tension in both groups of rats and the incidence of atrial arrest in the fasted rat group. The fall in the peak tension, lactate output and recovery upon reoxygenation were not altered by the inhibitor. These data indicate that methyl palmoxirate alleviates some of the hypoxic functional derangements. Hence, it may be inferred that inhibiting the oxidation of the fatty acid derived from the endogenous triacylglycerol is beneficial during oxygen-limited conditions and that these effects could not be ascribed to changes in the glycolytic flux.
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PMID:Effects of methyl palmoxirate on hypoxic rat atria. 130 33

We investigated the role of energy supplied by long-chain fatty acid oxidation in rat platelet function. Inhibition of the mitochondrial uptake of long-chain fatty acids was achieved by treating rats with 2-tetradecylglycidic acid (TDGA), a potent inhibitor of the overt form of carnitine palmitoyltransferase (CPT-I). The maximum aggregation rate (MAR), CPT-I activity, lactate production, oxygen consumption and adenine nucleotide content of isolated rat platelets were then studied in vitro. 4 h after the in vivo administration of TDGA, the CPT-I activity in saponin-permeabilized platelets was nearly completely inhibited along with a significant reduction in the MAR induced by ADP, thrombin and ionophore A23187. The ATP level, adenylate energy charge (ATP + 1/2 ADP)/(ATP + ADP + AMP) and ATP/ADP ratio in the platelet cytoplasmic pool were also reduced. Platelets from TDGA-treated rats showed lower oxygen consumption rates in both the basal respiratory and oxygen burst states. These results indicate that mitochondrial long-chain fatty acid oxidation coupled to oxidative phosphorylation is an important energy source in rat platelets and is probably involved in the maintenance of platelet function. Enhanced in vitro lactate production in platelets from TDGA-treated rats may have resulted from a compensatory increase in glycolysis which only partly compensated for impaired long-chain fatty acid oxidation.
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PMID:Effects of 2-tetradecylglycidic acid on rat platelet energy metabolism and aggregation. 142 Feb 90

Hepatic mitochondrial functions related to fatty acid metabolism, including the respiratory control ratio, fatty acid oxidative capacity and carnitine palmitoyltransferase I activity, were studied in vitro with mitochondria isolated from rats treated with thioacetamide for up to 12 wk. The levels of ketone bodies, carnitine, carnitine esters and malonyl-coenzyme A were also determined in liver extracts. Polarography of mitochondrial respiration from succinate or glutamate plus malate showed a lower respiratory control ratio in thioacetamide-treated rats, whereas uncoupled oxygen consumption was not altered. This suggests that the mitochondrial respiratory chain capacity remained intact in the thioacetamide-treated rats. The oxygen consumption associated with palmitoyl-coenzyme A and palmitoyl-L-carnitine oxidation by isolated liver mitochondria was increased by thioacetamide treatment on both a per-mitochondrial protein and a per-total liver basis. The carnitine palmitoyl-transferase I activity; the tissue levels of ketone bodies, carnitine and carnitine esters; and the beta-hydroxybutyrate/acetoacetate ratio were all higher in the livers of thioacetamide-treated animals than in control livers, whereas the hepatic malonyl-coenzyme A level was decreased by thioacetamide. These results indicate the increased diversion of cytosolic long-chain acyl-coenzyme As into the mitochondria for beta-oxidation rather than their esterification and use in lipogenesis. These intrahepatic metabolic changes induced by chronic thioacetamide administration may reflect the whole-body catabolic state and can be seen as adaptive for maintaining energy homeostasis under conditions of impaired glucose tolerance.
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PMID:Changes of hepatic fatty acid metabolism produced by chronic thioacetamide administration in rats. 159 50

The mechanisms by which noradrenaline, lipolytic agents and long-chain fatty acids stimulate glucose transport were investigated in rat brown adipocytes. Glucose transport was evaluated with tracer D-[U-14C]glucose and cell respiration was measured polarographically. Noradrenaline increased basal oxygen consumption (8-10-fold) and glucose transport (4-5-fold) in a dose-dependent manner, with a maximal stimulation at 100 nM. The stimulatory effects of noradrenaline on respiration and glucose transport were selectively mimicked by dibutyryl cyclic AMP (DBcAMP), 3-isobutyl-1-methylxanthine, cholera toxin and physiological concentrations of palmitic acid. Cytochalasin B completely blocked the effects of these agents on glucose transport. The beta-adrenergic antagonist propranolol inhibited noradrenaline-induced glucose transport, but did not affect the action of DBcAMP, palmitic acid or cholera toxin on this process. The specific inhibitor of mitochondrial carnitine palmitoyltransferase, 2-tetradecylglycidic acid (McN 3802) (50 microM), inhibited the stimulatory effects of noradrenaline (100 nM) and palmitic acid (0.5 mM) on both glucose transport and mitochondrial respiration. Significantly, McN 3802 failed to affect insulin (1 nM) action under identical experimental conditions. These results demonstrate that (a) the stimulatory effects of noradrenaline on brown-adipocyte respiration and glucose transport can be dissociated from those induced by insulin, and (b) noradrenaline increases glucose transport indirectly, by activating adenylate cyclase via beta-adrenergic pathways and by stimulating mitochondrial oxidation of fatty acids.
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PMID:Noradrenaline stimulates glucose transport in rat brown adipocytes by activating thermogenesis. Evidence that fatty acid activation of mitochondrial respiration enhances glucose transport. 171 31

Two groups of ventilated patients were compared for chest physical therapy on an ICU: respiratory insufficient patients on one side and a control population on the other were submitted either to percussion or vibration therapy, and to postural drainage. Our data show a decrease in arterial oxygen saturation after CPT and after 2h monitoring; the lateral position results in a better SaO2 in the pneumonia group while SaO2 tend to decrease in the control population. However, no significant therapeutic influence of vibration nor percussion was found. Our data suggest CPT does not result in a short term respiratory benefit. Further investigations with prolonged sessions of postural drainage are required.
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PMID:Influence of chest physiotherapy on arterial oxygen saturation. 176 27

Rat hepatic mitochondrial function, including oxidative phosphorylation, fatty acid oxidative capacity, kinetic parameters of carnitine palmitoyltransferase I (CPT I), and sensitivity of CPT I to malonyl-CoA inhibition were studied in vitro in isolated mitochondria following Escherichia coli lipopolysaccharide (LPS). The hepatic mitochondrial CPT I in LPS-treated rats showed a lower apparent maximum velocity (Vmax) for palmitoyl-CoA and Ki for malonyl-CoA without changes in apparent Km for palmitoyl-CoA. The rate of oxygen consumption or end-product formation of palmitoyl-L-carnitine and octanoate was not altered, but the rate of CPT I-dependent palmitoyl-CoA (plus L-carnitine) oxidation was reduced by LPS, when acetyl-CoA produced via beta-oxidation was directed toward citrate. When acetyl-CoA was directed to acetoacetate, the oxygen consumption rates of palmitoyl-L-carnitine and palmitoyl-CoA (plus L-carnitine) were decreased by LPS, although mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity was not altered. These results indicate that hepatic mitochondria isolated from LPS-treated rats show lower ketogenic and long-chain acyl-CoA oxidative capacity than those of fasted controls, and inhibition of ketogenesis is elicited at a site distal to CPT I in addition to reduction in CPT I activity.
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PMID:Altered hepatic mitochondrial fatty acid oxidation and ketogenesis in endotoxic rats. 222 Oct 51

The acylcarnitine transferase blocking agent, sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (Clomoxir, INN), effectively inhibits free fatty acid oxidation, thereby decreasing myocardial oxygen consumption in the normally perfused myocardium without influencing cardiodynamic parameters. As a consequence, however, arterial free fatty acid levels increase significantly. In an acute dog model, we investigated the hypothesis that the sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate-induced decrease in myocardial oxygen consumption may also improve the energetic situation in the underperfused myocardium. Regional myocardial function was assessed by means of subendocardially inserted ultrasonic crystals, and changes in metabolism were measured regionally by means of a catheter inserted into a local myocardial vein in the underperfused area. The flow in the circumflex coronary artery was reduced on average by 53.5% followed 30 min later by an infusion of sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (dosage: 20 mg/kg over 20 min). Arterial free fatty acid levels continuously increased, whereas arterial glucose levels decreased. In accordance with the situation in the normally perfused myocardium, free fatty acid uptake and oxygen uptake were also reduced in the underperfused area. However, sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate induced a further, transient increase in end-diastolic segment length and a sustained decrease in systolic shortening in the underperfused area, indicating a further deterioration in regional myocardial function. Control experiments with infusion of 9 g/l sodium chloride showed no change in the degree of regional myocardial dysfunction throughout the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of acylcarnitine transferase blockade on metabolism and function in the normally and underperfused canine myocardium. 238 Jun 72

Experimental data in animals indicate that coronary vasoconstriction occurs following blockade of the beta-adrenergic receptors or alpha-receptors activation. The vasomotor effects of these maneuvers in man are unclear. Therefore we investigated whether and to which extent alpha-stimulation (cold pressor test: CPT) and beta-blockade (propranolol) cause coronary vasoconstriction; whether this effect involves the resistance arterioles as well as the large epicardial branches, and, within these, whether the normal and stenotic tracts are involved. Patterns in patients with effort angina were compared with those in patients with Prinzmetal angina. We studied 19 cases with classic and 15 cases with Prinzmetal angina. The systemic, pulmonary and coronary hemodynamics (pressure, flow and resistance) and the vasomotor pattern of normal and stenotic epicardial branches (quantitative angiography) were evaluated in the baseline condition, during CPT, after propranolol (5 mg iv) and during CPT repeated after propranolol. We observed that: changes of the coronary flow due to beta-blockade and to CPT are related to the variations of the myocardial oxygen consumption, induced by the inhibition and activation of adrenergic receptors and not to the concomitant vasomotor reaction of the stenotic vascular tract; beta-blockade does not affect homogeneously the lumen of the stenotic lesions in effort angina and invariably increases the lumen in the Prinzmetal form; influences of CPT, in the absence as well as in the presence of beta-receptor blockade, on the lumen diameter of both normal vessels and stenotic lesions are minimal in either form of angina.
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PMID:[Activation and inhibition of adrenergic effects on the coronary vessels of patients with different forms of angina pectoris]. 255

Experiments were performed to further elucidate the role of gamma-amino-beta-hydroxybutyric acid trimethylbetaine (carnitine) on the metabolism and functions of spermatozoa. Addition of 20 mM L-carnitine to suspensions of ejaculated bovine spermatozoa resulted in an increase of cellular calcium transport, whereas 20 mM L-aminocarnitine (an inhibitor of carnitine palmitoyltransferase) caused an inhibition of this process. Both L-carnitine and L-aminocarnitine inhibited the progressive motility of spermatozoa, and the oxygen consumption as well as the release of the enzymes hyaluronidase and glutamate-oxaloacetate transaminase from spermatozoa. Labeled carnitine was rapidly taken up by spermatozoa by a process strongly dependent on temperature and extracellular concentration of carnitine. It is concluded that the effects produced by high concentrations of carnitine or aminocarnitine are mainly due to interactions of these compounds with the cellular membranes of spermatozoa.
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PMID:Effect of L-carnitine and L-aminocarnitine on calcium transport, motility, and enzyme release from ejaculated bovine spermatozoa. 262 59


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