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)

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.
 ...
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.
 ...
PMID:Effects of anandamide on hepatic fatty acid metabolism. 757 52

It has long been known that most of the energy production in the heart is derived from the oxidation of fatty acids. The other important sources of energy are the oxidation of carbohydrates and, to a lesser extent, ATP production from glycolysis. The contribution of these pathways to overall ATP production can vary dramatically, depending to a large extent on the carbon substrate profile delivered to the heart, as well as the presence or absence of underlying pathology within the myocardium. Despite extensive research devoted to the study of the individual pathways of energy substrate metabolism, relatively few studies have examined the integrated regulation between carbohydrate and fatty acid oxidation in the heart. While the mechanisms by which fatty acids inhibit carbohydrate oxidation (i.e., the Randle cycle) have been characterized, much less is known about how carbohydrates regulate fatty acid oxidation in the heart. It is clear that an increase in intramitochondrial acetyl-CoA derived from carbohydrate oxidation (via the pyruvate dehydrogenase complex) can downregulate beta-oxidation of fatty acids, but it is not clear how fatty acid acyl group entry into the mitochondria is downregulated when carbohydrate oxidation increases. Recent interest in our laboratory has focused on the involvement of acetyl-CoA carboxylase (ACC) in this process. While it has been known for some time that malonyl-CoA does exist in heart tissue, and that it is a potent inhibitor of carnitine palmitoyltransferase 1 (CPT 1), it has only recently been demonstrated that an isoenzyme of ACC exists in the heart that is a potential source of malonyl-CoA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The 1993 Merck Frosst Award. Acetyl-CoA carboxylase: an important regulator of fatty acid oxidation in the heart. 788 73

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)
 ...
PMID:Effects of lovastatin on hepatic fatty acid metabolism. 790 61

Incubation of hepatocytes under conditions known to increase their volume, i.e. with amino acids (glutamine, proline) or in hypo-osmotic medium, decreased carnitine palmitoyl-transferase I (CPT-I) activity. This effect of hepatocyte swelling was antagonized by okadaic acid and dibutyryl-cAMP. Physiological concentrations of glutamate inhibited CPT-I activity in digitonin-permeabilized hepatocytes but not in isolated mitochondria. Results suggest that the amino acid-induced inhibition of CPT-I shares a common mechanism with the amino acid-induced stimulation of acetyl-CoA carboxylase and glycogen synthase [(1993) Eur. J. Biochem. 217, 1083-1089].
 ...
PMID:Inhibition of carnitine palmitoyltransferase I by hepatocyte swelling. 791 May 67

The effects of the ingestion of a meal on the partitioning of hepatic fatty acids between oxidation and esterification were studied in vivo for meal-fed rats. The time course for the reversal of the starved state was extremely rapid and the process was complete within 2 h, in marked contrast with the reversal of the effects of starvation in rats fed ad libitum [A. M. B. Moir and V. A. Zammit (1993) Biochem. J. 289, 49-55]. This rapid reversal occurred in spite of the fact that, in the liver of the meal-fed animals before feeding, a similar degree of partitioning of fatty acids in favour of oxidation was observed as in 24 h-starved rats (previously fed ad libitum). This suggested that the lower degree of ketonaemia observed in meal-fed rats before a meal is not due to the inability of acylcarnitine formation to compete successfully with esterification of fatty acids to the glycerol moiety. Investigation of the possible mechanisms that could contribute towards the rapid switching-off of fatty acid oxidation revealed that this was correlated with a very rapid rise and overshoot in hepatic malonyl-CoA concentration, but not with any change in the activity, or sensitivity to malonyl-CoA, of the mitochondrial overt carnitine palmitoyltransferase (CPT I). The role of these two parameters in the reversal of fasting-induced hepatic fatty acid oxidation was thus the inverse of that observed previously for refed 24 h-starved rats. The rapid increase in [malonyl-CoA] was accompanied by an immediate and complete reversion of the kinetic characteristics (Ka for citrate, expressed/total activity ratio) of acetyl-CoA carboxylase to those found in the post-meal animals, again in contrast with the time course observed in refed 24 h-starved rats [A. M. B. Moir and V. A. Zammit (1990) Biochem. J. 272, 511-517]. The rapidity with which these changes occurred was specific to the partitioning of acyl-CoA; the meal-induced diversion of glycerolipids towards phospholipid synthesis and the acute inhibition of the fractional rate of triacylglycerol secretion occurred with very similar time courses to those observed upon refeeding of 24 h-starved rats. The results confirm the central role played by differences in the dynamics of changes in hepatic malonyl-CoA concentration, and CPT I sensitivity to it, in determining the route through which ingested glucose is converted into hepatic glycogen upon refeeding of starved rats which had previously been meal-fed or fed ad libitum.
 ...
PMID:Rapid switch of hepatic fatty acid metabolism from oxidation to esterification during diurnal feeding of meal-fed rats correlates with changes in the properties of acetyl-CoA carboxylase, but not of carnitine palmitoyltransferase I. 809 87

We examined changes in the enzyme activities and metabolites related to hepatic fatty acid synthesis in fasted rats with sepsis produced by cecal ligation and puncture. Sepsis stimulated the in vivo incorporation of tritiated water into hepatic fatty acids and nonsaponifiable lipids. The activities of acetyl-CoA carboxylase, ATP-citrate lyase, and NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and malic enzyme), the tissue levels of citrate and malonyl-CoA, and the dephosphorylation of carboxylase were increased in the livers of fasted septic rats compared with fasted sham-operated control rats. These results indicate that sepsis stimulated hepatic lipogenesis and sterologenesis in fasting rats. Furthermore, sepsis reduced the specific activity of hepatic mitochondrial carnitine palmitoyltransferase and raised that of glycerophosphate acyltransferase, suggesting an increased diversion of cytosolic acyl-CoA towards esterification. These intrahepatic metabolic changes strongly suggest that sepsis causes anabolic action on hepatic lipid metabolism.
 ...
PMID:Accelerated hepatic lipid synthesis in fasted septic rats. 809 11

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.
 ...
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.
 ...
PMID:Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation. 821 40

Administration of tetradecylthioacetic acid (a 3-thia fatty acid) increases mitochondrial and peroxisomal beta-oxidative capacity and carnitine palmitoyltransferase activity, but reduces free fatty acid and triacylglycerol levels in plasma compared to palmitic acid-treated rats and controls. The decrease in plasma triacylglycerol was accompanied by a reduction (56%) in VLDL-triacylglycerol. Prolonged supplementation of tetradecylthioacetic acid caused a significant increase in lipogenic enzyme activities (ATP-citrate lyase and acetyl-CoA carboxylase) and diacylglycerol acyltansferase, but did not affect phosphatidate phosphohydrolase. Plasma cholesterol, LDL- and HDL-cholesterol levels were reduced. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity was, however, stimulated in 3-thia fatty acid-treated rats compared to controls. In addition. the mRNAs of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and LDL-receptor were increased. Tetradecylthioacetic acid administration affected the fatty acid composition in plasma and liver by increasing the amount of monoenes, especially 18:1(n-9), mostly at the expense of omega-3 fatty acids. Compared to liver a large amount of tetradecylthioacetic acid accumulated in the heart, and this accumulation was accompanied by an increase in omega-3 fatty acids, particularly 22:6(n-3) and a decrease in omega-6 fatty acids, mainly 20:4(n-6). The results show that the hypolipidemic effect of tetradecylthioacetic acid is sustained after prolonged administration and may, at least in part, be due to increased fatty acid oxidation and upregulated LDL-receptor gene expression. The increase in lipogenic enzyme activities as well as increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, may be compensatory mechanisms to maintain cellular integrity. Decreased level of 20:4(n-6) combined with increased omega-3/omega-6 ratio in cardiac tissue after tetradecylthioacetic acid treatment may have influence on membrane dynamics and function.
 ...
PMID:Long-term effect of tetradecylthioacetic acid: a study on plasma lipid profile and fatty acid composition and oxidation in different rat organs. 865 42


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