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)

1. Extracellular field potentials were recorded to study the role of endogenous adenosine during hypoxia in area CA1 of rat hippocampal slices. 2. Hypoxic conditions, induced by 15 min exposure to 95% N2-5% CO2 at 32 degrees C and in high-glucose incubation medium, produced a rapid and reversible depression of evoked synaptic potentials. 3. In slices from young Sprague-Dawley rats, the hypoxia-induced synaptic depression was reduced in a concentration-dependent manner by the adenosine antagonist 8-cyclopentyltheophylline (8-CPT; 100 nM-2.0 microM). 4. Recovery of synaptic potentials after hypoxia was complete under each experimental condition. 5. Extended periods of hypoxia lasting 30 min likewise produced a rapid and near total suppression of the evoked synaptic potentials. In the presence of 8-CPT, both the population excitatory postsynaptic potential (EPSP) slope and population spike amplitude were significantly preserved throughout the hypoxic episode. 6. Neither the onset rate nor the degree of the hypoxia-induced synaptic depression were significantly different in slices from young, adult, or aged Fischer 344 rats. Reduction of the hypoxia-induced response depression by 8-CPT was also similar in all age groups. 7. These findings have further characterized the important involvement of endogenous adenosine in the potentially neuroprotective synaptic depression observed in hippocampal slices from young and aged rats during hypoxia.
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PMID:Endogenous adenosine contributes to hypoxic synaptic depression in hippocampus from young and aged rats. 152 79

Objectives of this study were to quantitate metabolite fluxes in ruminant liver and to delineate effects of recombinant bST on patterns of nutrient metabolism by liver. Nineteen multiparous cows ranging in previous lactational performance from 6400 to 13,500 kg per 305-d lactation were treated with either placebo or bST (40 mg/d) from wk 11 to 18 of lactation. Liver tissue was collected at slaughter. Tissue slices were incubated with various 14C-labeled substrates, and rates of conversion of label to CO2 and metabolites were measured. In vivo recombinant bST treatment increased in vitro conversion of [1-14C]propionate and [2-14C]acetate to glucose more than twofold. At 2.5 mM propionate, bST-treated cows converted propionate to glucose at 90% efficiency. Recombinant bST increased [14C]bicarbonate incorporation into glucose five-fold. Overall, bST treatment resulted in greater C flow from propionate and acetate through the TCA cycle. Acetate had only small effects on propionate metabolism and no effects on lactate plus pyruvate metabolism. Unexpectedly, propionate decreased acetate conversion to ketone bodies. Suggested mechanisms for this observation include depletion of coenzyme A and allosteric regulation of carnitine palmitoyltransferase I by methylmalonyl-coenzyme A formed from propionate. In summary, bST treatment resulted in increased rates of gluconeogenesis and oxidation in liver in support of lactation.
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PMID:Effects of somatotropin and substrates on patterns of liver metabolism in lactating dairy cattle. 157 17

Tissues of fasted animals treated with L-aminocarnitine (L-3-amino-4-trimethylaminobutyrate) showed an accumulation of long-chain acylcarnitines and triacylglycerols. Blood levels of free fatty acids, long-chain acylcarnitines and triacylglycerol-rich lipoproteins were found to be increased, whereas glucose was reduced. The liver mitochondria isolated from rats treated with L-aminocarnitine utilized both pyruvate and succinate normally, but were not able to oxidize palmitoylcarnitine. In vitro oxidation of palmitoylcarnitine by liver mitochondria was inhibited by L-aminocarnitine in a concentration-dependent fashion in contrast to succinate and pyruvate oxidation which was not modified. L-aminocarnitine proved to be a potent and selective inhibitor (IC50 = 805 nM) of the carnitine palmitoyltransferase isoenzyme, located on the inner side of the mitochondrial inner membrane (CPT2). The activity of the carnitine palmitoyltransferase isoenzyme located on the mitochondrial outer membrane inhibitable by malonyl-CoA (IC50 = 19 microM), was not inhibited by 0.8 microM L-aminocarnitine. Both in vitro and in vivo effects of L-aminocarnitine suggest that the substance has a specific and potent inhibitory action on CPT2. Its in vivo inhibition results in a dramatic increase of long-chain acylcarnitines in various organs, that it is why this increase can be considered a very good marker of CPT2 inhibition. A markedly altered lipid metabolism was observed.
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PMID:Tissue lipid accumulation by L-aminocarnitine, an inhibitor of carnitine-palmitoyltransferase-2. Studies in intact rats and isolated mitochondria. 162 37

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

The present study was designed to evaluate the effects of POCA, a carnitine palmitoyltransferase I (CPT I) inhibitor, and pyruvate, a substrate inhibiting fatty acid (FA) oxidation, on post-ischemic cardiac FA accumulation on the one hand, and hemodynamic recovery and loss of cellular integrity on the other. To this end isolated, working rat hearts, receiving glucose (11 mM) as substrate, were subjected to 45 min of no-flow ischemia and 30 min of reperfusion. Hearts were perfused with or without POCA (10 microM) and/or pyruvate (5 mM). In the control group the FA content increased significantly during ischemia and remained elevated during reperfusion. Administration of POCA did not affect functional recovery and LDH release significantly, but resulted in about two-fold increased FA levels upon reperfusion as compared to glucose-perfused hearts. Pyruvate markedly improved functional recovery. Addition of this substrate did not affect lactate dehydrogenase (LDH) release, but enhanced FA accumulation during reperfusion. The combined administration of pyruvate and POCA nullified the positive effect of pyruvate on hemodynamic recovery, aggravated LDH release, and further enhanced the accumulation of FAs. The adenine nucleotide content of reperfused hearts was comparable for all groups investigated. In conclusion, during transient ischemia POCA and pyruvate markedly increased cardiac FA accumulation through inhibition of the oxidation of FAs released from endogenous lipid pools. No clear relation was found between the FA content of reperfused hearts and post-ischemic functional recovery.
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PMID:Fatty acid accumulation during ischemia and reperfusion: effects of pyruvate and POCA, a carnitine palmitoyltransferase I inhibitor. 181 Oct 59

Humans who lack availability of carbohydrate fuels may provide important models for the study of physiological control mechanisms. We compared seven patients who had unavailability of muscle glycogen and blood glucose as oxidative fuels due to muscle phosphofructokinase deficiency (PFKD) with five patients who had a selective defect in long-chain fatty acid oxidation due to carnitine palmitoyltransferase deficiency (CPTD) and with six healthy subjects. Peak cycle exercise work rate, peak O2 uptake (Vo2), and arteriovenous O2 difference were markedly lower (P less than 0.001) for PFKD patients (23 +/- 6 W, 14 +/- 2 ml.min-1.kg-1, and 7.1 +/- 0.5 ml/dl, respectively) than for CPTD patients (142 +/- 33 W, 31 +/- 4 ml.min-1.kg-1, and 15.0 +/- 0.8 ml/dl, respectively) or healthy subjects (171 +/- 17 W, 36 +/- 1 ml.min-1.kg-1, and 16.4 +/- 0.7 ml/dl, respectively). Peak cardiac output (Q) was similar (P less than 0.05) in all three groups, but the slope of increase in Q (l/min) on Vo2 (l/min) from rest to exercise (delta Q/ delta Vo2) was more than twofold greater (P less than 0.001) for PFKD patients (11.2 +/- 1.2) than for CPTD patients (4.6 +/- 0.6) and healthy subjects (4.6 +/- 0.2). Increasing availability of blood-borne oxidative substrates capable of metabolically bypassing the defect at phosphofructokinase (by fasting plus prolonged moderate exercise to increase plasma free fatty acids or by iv lactate infusion) increased peak work rate, Vo2, and arteriovenous O2 difference, lacked consistent effect on peak Q, and normalized delta Q/ delta Vo2 in PFKD patients. The results extend our previous observations in patients with a block in muscle glycogen but not blood glucose oxidation due to phosphorylase deficiency and imply that specific unavailability of muscle glycogen as an oxidizable fuel is primarily responsible for abnormal muscle oxidative metabolism and associated exercise intolerance and exaggerated delta Q/ delta Vo2 in muscle PFKD. The findings also endorse the concept that factors closely linked with muscle oxidative phosphorylation participate in regulating delta Q/ delta Vo2, likely via activation of metabolically sensitive muscle afferents.
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PMID:Abnormal oxidative metabolism and O2 transport in muscle phosphofructokinase deficiency. 182 93

Epidemiological studies have clearly shown that the so-called metabolic syndrome which is linked to insulin resistance and a reduced glucose utilization of muscle represents an important risk factor for cardiovascular disease. However, only little is known of the intracellular consequences of insulin resistance. An important feature of an altered substrate utilization is related to signal transduction of gene expression. For the example of myosin heavy chain expression, it is shown that metabolic signals exist which reflect the fuel flux and substrate utilization of the heart muscle cell. The signals were characterized in functional states of the heart associated with altered metabolic influences (fasting, diabetes, sucrose feeding, increased calorie intake, carnitine palmitoyltransferase inhibition). In the pressure-overloaded heart, metabolic interventions which are expected to increase glucose utilization (sucrose feeding, captopril treatment) have a pronounced effect. Although a link with gene expression remains to be established, it should be noted that the sarcoplasmic reticulum Ca(2+)-pump activity seems to be affected in a functionally comparable manner. It is concluded that metabolic signals alter the protein phenotype of heart muscle and it is expected that a deranged signal transduction affects, not only the heart, but also vascular muscle.
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PMID:The metabolic syndrome and signal transduction of gene expression. 183 54

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

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

Hummingbirds in flight display the highest rates of aerobic metabolism known among vertebrates. Their flight muscles possess sufficient maximal activities of hexokinase and carnitine palmitoyltransferase to allow the exclusive use of either glucose or long-chain fatty acids as metabolic fuels during flight. Respiratory quotients (RQ = VCO2/VO2) indicate that fatty acid oxidation serves as the primary energy source in fasted resting birds, while subsequent foraging occurs with a rapid shift towards the use of carbohydrate as the metabolic fuel. We suggest that hummingbirds building up fat deposits in preparation for migration behave as carbohydrate maximizers (or fat minimizers) with respect to the metabolic fuels selected to power foraging flight.
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PMID:Fuel selection in rufous hummingbirds: ecological implications of metabolic biochemistry. 225 Dec 66


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