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)

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

Periportal and perivenous hepatocytes were isolated from rats subjected to different treatments that induce (starvation, cold exposure) or depress (refeeding after starvation) hepatic fatty acid oxidation. These experiments were designed to determine factors that may be involved in creating and maintaining the asymmetrical distribution of this metabolic pathway in the acinus of the liver. The uneven distribution of mitochondrial [14C]-palmitate oxidation within the acinus (i) was very flexible and changed markedly with the physiological status of the animal (periportal/perivenous ratio: 1.5, 2.0, 1.0 and 0.4 for fed, starved, refed and cold-exposed animals respectively), (ii) coincided with a similar zonation of carnitine palmitoyltransferase I activity in fed as well as in cold-exposed animals, (iii) was paralleled by a comparable zonation of mitochondrial 3-hydroxy-3-methyl-glutaryl-CoA synthase activity in starved animals, and (iv) was not determined by zonal differences in any of the following parameters: sensitivity of carnitine palmitoyltransferase I to malonyl-CoA, intracellular concentration of malonyl-CoA, fatty acid synthesizing capacity, acetyl-CoA carboxylase activity, fatty acid synthase activity or relative content of the two hepatic acetyl-CoA carboxylase isoforms. Unlike mitochondrial oxidation, peroxisomal [14C]palmitate oxidation was always zonated towards the perivenous zone of the liver irrespective of the physiological status of the animal. The data presented show that changes in the acinar distribution of mitochondrial long-chain fatty acid oxidation involve specific long-term mechanisms under different physiological conditions.
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PMID:Flexibility of zonation of fatty acid oxidation in rat liver. 748 41

Incubation of rat hepatocytes with anandamide (arachidonoylethanolamide) inhibited acetyl-CoA carboxylase activity and fatty acid synthesis de novo without affecting fatty acid synthase. This was concomitant to a decrease in the intracellular levels of malonyl-CoA. Likewise, anandamide depressed both cholesterol synthesis de novo and the incorporation of exogenous palmitate into triacylglycerols and phospholipids. On the other hand, anandamide stimulated in parallel both carnitine palmitoyltransferase I activity and ketogenesis from palmitate, though ketogenesis from octanoate was unaffected. The effects of anandamide on hepatic fatty acid synthesis and oxidation were: (a) mimicked by arachidonic acid, a product of anandamide breakdown by anandamide amidase; (b) prevented by phenylmethylsulfonyl fluoride, an inhibitor of anandamide amidase; and (c) not affected by bisindolylmaleimide, a specific inhibitor of protein kinase C. Furthermore, delta 9-tetrahydrocannabinol had no effect on any of the parameters determined, ruling out the possibility that the effects of anandamide on hepatic fatty acid metabolism are mediated by the peripheral cannabinoid receptor. The results thus indicate that anandamide might function as a carrier of arachidonic acid in the modulation of hepatic fatty metabolism.
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PMID:Effects of anandamide on hepatic fatty acid metabolism. 757 52

The in vitro and in vivo effects of lovastatin on fatty acid metabolism were studied in isolated rat hepatocytes. When added in vitro to cell incubations, lovastatin stimulated de novo fatty acid synthesis and acetyl-CoA carboxylase activity, whereas fatty acid synthase activity was unaffected. Lovastatin depressed palmitate, but not octanoate, oxidation. This may be attributed to the lovastatin-induced increase in intracellular malonyl-CoA levels, as no concomitant change of carnitine palmitoyltransferase I (CPT-I) specific activity was detected. Lovastatin had no effect on the synthesis and secretion of triacylglycerols and phospholipids in the form of very low density lipoproteins (VLDL). When rats were fed a diet supplemented with 0.1% (w/w) lovastatin for one week, both acetyl-CoA carboxylase activity and de novo fatty acid synthesis were reduced compared to pair-fed controls, whereas fatty acid synthase activity was unaffected. Palmitate oxidation was enhanced in the lovastatin-fed group. There was an increase in CPT-I activity but no change in intracellular concentration of malonyl-CoA. Lovastatin feeding had no significant effect either on the esterification of exogenous palmitic acid into both cellular and VLDL triacylglycerols and phospholipids or on hepatic lipid accumulation. The in vitro and in vivo effects of lovastatin were not significantly different between periportal and perivenous hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of lovastatin on hepatic fatty acid metabolism. 790 61

Levels of mRNA for mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II), fatty acid synthase (FAS) and actin were analysed during liver regeneration. mRNA levels for mitochondrial HMG-CoA synthase decreased rapidly, reaching a minimum 12 h after partial hepatectomy and returning to normal at 24-36 h. In contrast, CPT I, CPT II and FAS mRNAs increased throughout the period examined. Expression of actin increased significantly during regeneration. Levels of mRNA for mitochondrial HMG-CoA synthase also decreased as a result of surgical stress, although the effect of hepatectomy was much greater. We determined the levels of mitochondrial HMG-CoA synthase using specific antibodies. The amount of protein rapidly decreased, although less markedly than the corresponding mRNA levels. These results show that the decrease described in ketogenesis in partially hepatectomized rats correlated with the decrease in the expression of mitochondrial HMG-CoA synthase, suggesting that this enzyme may also be a control point in ketogenesis in the regenerating liver, as it is in normal and diabetic rats.
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PMID:Gene expression of enzymes regulating ketogenesis and fatty acid metabolism in regenerating rat liver. 790 32

Proglycosyn (LY177507) belongs to a series of powerful agents that stabilize liver glycogen stores by promoting glycogen synthesis from different precursors and inhibiting glycogenolysis and glycolysis. In the present study we have examined the effects of proglycosyn on fatty acid metabolism in isolated hepatocytes. Preincubation of hepatocytes with medium containing proglycosyn led to a marked inhibition of fatty acid synthesis de novo and acetyl-CoA carboxylase activity without affecting fatty acid synthase. Likewise, proglycosyn depressed the synthesis of triacylglycerols and phospholipids from labeled palmitate. Although octanoate oxidation was unaffected by proglycosyn, mitochondrial palmitate oxidation was notably stimulated. This effect may be attributed to the proglycosyn-induced decrease of intracellular malonyl-CoA levels relative to control incubations and the concomitant relieve of the inhibition of the mitochondrial-outer-membrane carnitine palmitoyl-transferase by malonyl-CoA. By contrast, neither peroxisomal palmitate oxidation nor peroxisomal carnitine palmitoyltransferase activity was changed upon hepatocyte incubation with proglycosyn. Results thus indicate that proglycosyn increases the fatty-acid-oxidation efficiency of the liver at the expense of lipogenesis, and this may contribute to the proglycosyn-induced sparing of liver glycogen stores.
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PMID:Effects of proglycosyn (LY177507) on fatty acid metabolism in rat hepatocytes. 810 45

1. Viable myocytes were obtained from rat hearts. Oxidation of [1-14C]palmitate by these cells could be decreased by the addition of glucose (5 mM) or lactate (2 mM). In the presence of glucose, insulin decreased and adrenaline increased palmitate oxidation. 2. The myocytes contained activities of ATP citrate-lyase, acetyl-CoA carboxylase and the condensing enzyme of the fatty acid elongation system. No fatty acid synthase activity was demonstrable in myocytes. 3. In rat hearts perfused with 5 mM glucose, malonyl-CoA content was acutely raised by insulin. In the presence of glucose+insulin, perfusion with palmitate or adrenaline decreased the malonyl-CoA content. 4. It is concluded that malonyl-CoA can be synthesized within cardiac myocytes and that the level of this metabolite can be acutely regulated. This is likely to have consequences for the regulation of carnitine palmitoyltransferase in the heart.
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PMID:Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation. 821 40

This study was conducted to examine whether nitric oxide regulates lipid metabolism. In Experiment 1, rats were fed for 5 wk diets with or without 0.2 g/kg L-N-nitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase, that were or were not supplemented with 40 g/kg L-arginine. Rats fed L-NNA had significantly higher concentrations of serum triglyceride and total cholesterol, lower concentrations of serum nitrate, and a lower ratio of HDL-cholesterol to total cholesterol than rats fed the basal diet. These alterations were suppressed by supplementing L-arginine to the L-NNA-containing diet. In Experiment 2, rats were fed diets with or without 0.2 g/kg L-NNA. Dietary L-NNA elevated serum concentrations of free fatty acids without affecting those of ketone bodies. L-NNA lowered the activity of hepatic carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, but did not affect activities of hepatic glucose-6-phosphate dehydrogenase and fatty acid synthase which are lipogenic enzymes. These results suggest that the lower nitric oxide level in rats fed L-NNA leads to hyperlipidemia and that the elevation in serum triglyceride might be due to reduced fatty acid oxidation.
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PMID:Feeding rats the nitric oxide synthase inhibitor, L-N(omega)nitroarginine, elevates serum triglyceride and cholesterol and lowers hepatic fatty acid oxidation. 885 18

The aim was to investigate if chronic feeding with oligofructose (OFS), a nondigestible fructan that decreases triacylglycerol-very-low-density lipoproteins (TAG-VLDLs) in the serum of rats by reducing hepatic de novo lipogenesis, could counteract the impact of fructose on TAG metabolism. Male Wistar rats fed a standard diet supplemented or not with 10% OFS for 30 days received either tap water or a 10% fructose drinking solution for 48 hours. TAG, phospholipids (PLs), cholesterol, and free fatty acids were assayed both in serum and in liver. Fatty acid de novo synthesis, esterification, and beta-oxidation were assessed in the liver by measuring the activity of key enzymes: fatty acid synthase (FAS), phosphatidate phosphohydrolase (PAP), glycerol-3-phosphate acyltransferase (GPAT), and carnitine palmitoyltransferase-I (CPT-I), respectively. The acute load of fructose increased (1) both liver and serum TAG without affecting other lipids, and (2) de novo fatty acid synthesis and esterification, through induction of FAS and PAP without affecting CPT-I. Long-term feeding with OFS protected rats against liver TAG accumulation induced by fructose. The lower lipogenic capacity of the liver could be the key event in this protection, since even after the fructose load FAS activity remained significantly lower in OFS-fed rats. However, despite its protective effect on the liver, OFS was not able to prevent fructose-induced hypertriglyceridemia, suggesting that OFS feeding could not counteract the fructose-induced defect in TAG-VLDL clearance.
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PMID:Dietary oligofructose modifies the impact of fructose on hepatic triacylglycerol metabolism. 896 90

The effects of dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids on the enzyme activities related to hepatic lipogenesis and beta-oxidation were compared under constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 ratios of dietary fats in rats. Dietary fat containing linoleic acid as the sole polyunsaturated fatty acid (PUFA) was also given as a control. The concentration of serum triglyceride and phospholipid in the three n-3 PUFA groups was lower than in the linoleic acid group. The hepatic triglyceride concentration was lower and the phospholipid concentration was higher in the three n-3 PUFA groups than in the linoleic acid group. Cytosolic fatty acid synthase (FAS) activity was lower in the n-3 PUFA groups than in the linoleic acid group, the reduction being more predominant in the eicosapentaenoic acid and docosahexaenoic acid groups than in the alpha-linolenic acid group. The cytosolic activities of the NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and the malic enzyme, were lower in the three n-3 PUFA groups. The activity of carnitine palmitoyltransferase (CPT) in mitochondria was higher only in the eicosapentaenoic acid group than in the other groups. The activity of Mg(2+)-dependent phosphatidate phosphohydrolase (PAP) in microsomes and cytosol was lower in the eicosapentaenoic and docosahexaenoic acid groups than in the linoleic acid group, while there was no effect of dietary fats on the activities of diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (G3PAT) in microsomes. The CTP: phosphocholine cytidylyltransferase (CT) activity in the homogenate was lower in the n-3 PUFA groups, the reduction being more prominent in the eicosapentaenoic and docosahexaenoic acid groups than in the alpha-linolenic acid group. The choline kinase (CK) activity in cytosol was lower in the eicosapentaenoic acid group than in the linoleic acid group. These results showed that dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids differently influenced hepatic lipogenesis and the partition of fatty acid into oxidation or glycerolipid synthesis.
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PMID:Effects of dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids on hepatic lipogenesis and beta-oxidation in rats. 961 98


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