Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the study was to separate the mitochondrial proteins of rat Walker 256 tumour tissue and perform immunodetection studies to identify the carnitine palmitoyltransferase I (CPT I) and CPT II proteins previously reported to be present in this tumour. CPT I protein was undetectable using antibody raised against rat liver CPT I and was therefore considered to be immunologically different from that found in normal rat tissues such as heart, liver and skeletal muscle. In contrast, CPT II protein was readily detected in Walker 256 tumour and had an apparent Mr of approximately 70,000, as was found for rat liver. The in vivo treatment of tumour-bearing rats with insulin caused an increase in the expression of CPT II protein in the tumour tissue. The data confirm that CPT II can be regulated by insulin and also demonstrate that tumour CPT I may be a different isoform from that present in rat liver.
Biochem Mol Biol Int 1996 Feb
PMID:Immunodetection of rat Walker 256 tumour mitochondrial carnitine palmitoyltransferase I and II: evidence for the control of CPT II expression by insulin. 893 31

The effects of two cell-permeable cyclic AMP analogues, 8-chloro cyclic AMP (8-Cl cAMP) and 8-(4-chlorophenylthio) cyclic AMP (8-CPT cAMP), on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis were compared in cultured rat and hamster hepatocytes. Cholesterol esterification, as measured by the incorporation of [3H]oleate into cholesteryl ester, was increased by 58-88% by the analogues in rat hepatocytes and by 33-43% in hamster cells. The response in rat hepatocytes, however, was observed after a relatively short incubation time (28% increase after 1 hr), whereas that in hamster cells required a longer period (36% after 12 hr) to become apparent. The activity of the cytosolic neutral cholesteryl ester hydrolase in rat hepatocytes was also stimulated by both cyclic AMP analogues (31-37%, but the microsomal activity was unaffected. In hamster hepatocytes, however, microsomal cholesteryl ester hydrolase activity was increased (47-80%) in the presence of 8-Cl cAMP or 8-CPT cAMP. Bile acid synthesis was increased by 8-CPT cyclic AMP in rat cells (approximately 25%) but was unchanged by both analogues in hamster hepatocytes. These results indicate significant differences in the way in which cholesterol metabolism responds to cyclic AMP in cultured rat and hamster hepatocytes.
Comp Biochem Physiol B Biochem Mol Biol 1996 Jan
PMID:Comparison of the effects of cyclic AMP analogues on cholesterol metabolism in cultured rat and hamster hepatocytes. 893 53

Previous studies have reported the presence of carnitine palmitoyltransferase I and II in tumor cells and the inhibitory effects of fatty acids on cell proliferation. The present work considered the metabolic fate of [14C] or [3H]-labeled fatty acids and their effects on cellular metabolism in Hep2 human larynx tumor cells. The rate of uptake of acetate was 45% of that of myristate, palmitate, oleate, linoleate and arachidonate. However, acetate was rapidly metabolized within the cell as seen by its low rate of accumulation as non-esterified fatty acid, < 5% of that of the other fatty acids. The incorporation of fatty acids into neutral lipid fractions showed palmitate and oleate primarily entered the phospholipid fraction, while linoleate and arachidonate entered equally the phospholipid and triacylglycerol fractions. Palmitate and oleate were oxidized to 14CO2 at higher rates than linoleate and arachidonate, with arachidonate being the least oxidized of the unsaturated fatty acids. Acetate was oxidized at 10-30 fold higher rates than the other fatty acids. Palmitate, oleate, linoleate and arachidonate all had significant inhibitory effects on the rate of glucose utilization by Hep2 cells, ranging from 25-38% inhibition and were found to inhibit cell proliferation by 17-73%. These findings suggest that certain fatty acids not only play a structural role in cellular metabolism, but may also have a potential regulatory role in the glycolytic pathway of Hep2 cells.
Biochem Mol Biol Int 1997 Mar
PMID:Metabolic fate and effects of saturated and unsaturated fatty acids in Hep2 human larynx tumor cells. 909 Apr 68

This study was designed to determine if acute (in vitro) or chronic (in vivo) adriamycin inhibits cardiac fatty acid oxidation and if so at what sites in the fatty acid oxidation pathway. In addition, the role of L-carnitine in reversing or preventing this effect was examined. We determined the effects of adriamycin in the presence or absence of L-carnitine on the oxidation of the metabolic substrates [1-14C]palmitate. [1(-14)C] octanoate. [1(-14)C]butyrate, [U-14C]glucose, and [2(-14)C]pyruvate in isolated cardiac myocytes. Acute exposure to adriamycin caused a concentration- and time-dependent inhibition of carnitine palmitoyl transferase 1 (CPT 1) dependent long-chain fatty acid, palmitate, oxidation. Chronic exposure to (18 mg/kg) adriamycin inhibited palmitate oxidation 40% to a similar extent seen in vitro with 0.5 mM adriamycin. Acute or chronic administration of L-carnitine completely abolished the adriamycin-induced inhibition of palmitate oxidation. Interestingly, medium- and short-chain fatty acid oxidation, which are independent of CPT 1, were also inhibited acutely by adriamycin and could be reversed by L-carnitine. In isolated rat heart mitochondria, adriamycin significantly decreased oxidation of the CPT 1 dependent substrate palmitoyl-CoA by 50%. However, the oxidation of a non-CPT 1 dependent substrate palmitoylcarnitine was unaffected by adriamycin except at concentrations greater than 1 mM. These data suggest that after in vitro or in vivo administration, adriamycin, inhibits fatty acid oxidation in part secondary to inhibition of CPT 1 and/or depletion of its substrate, L-carnitine, in cardiac tissue. However, these findings also suggest that L-carnitine plays an additional role in fatty acid oxidation independent of CPT 1 or fatty acid chain length.
J Mol Cell Cardiol 1997 Feb
PMID:Acute and chronic effects of adriamycin on fatty acid oxidation in isolated cardiac myocytes. 914 Aug 35

Four missense mutations have been reported to be associated with the typical, adult form of carnitine palmitoyltransferase II (CPT II) deficiency: Three amino acid substitutions (R631C. P50H and D553N) appear to be rare, while the S113L mutation was found to be common in a group of European patients with CPT II deficiency. We analyzed genomic DNA from 20 American patients with recurrent episodes of myoglobinuria as well as DNA from 10 normal controls in order to determine the frequency of the reported missense mutations in our patient population. The three previously described rare mutations were not found in our group of patients. The S113L mutation was found in 19 of our patients: 5 patients were homozygous, 14 patients were heterozygous. Given the high frequency of this mutation in our series of patients we concluded that the clinical diagnosis of CPT II deficiency can be confirmed by a 'blood test' without resorting to a muscle biopsy.
Mol Cell Biochem 1997 Sep
PMID:Carnitine palmitoyltransferase II deficiency: diagnosis by molecular analysis of blood. 930 94

Fatty acids have been shown to regulate the expression of mRNA for both lipogenic and glycolytic enzymes in rat liver. The role of fatty acids in the regulation of carnitine palmitoyltransferase (CPT) I and II activity in tumour cells was investigated. The polyunsaturated fatty acids, gamma-linolenic and arachidonic acid, caused 60-70% inhibition of tumour cell CPT I activity and 45-50% inhibition of [14C]-palmitic acid oxidation to 14CO2. These effects were blocked by the cyclooxygenase inhibitor, indomethacin. Prostaglandins E1 and E2 caused marked inhibition of both CPT I and CPT II activity and inhibition of cell proliferation. Prostaglandin E2 production by tumour cells was increased in the presence of arachidonic acid and inhibited when indomethacin was present. The proliferation of the HT29 cell line was unaffected as was its CPT I and II activity by both fatty acids and prostaglandins. CPT I mRNA expression was not inhibited by fatty acids, indeed it increased-in the presence of arachidonic acid and prostaglandin E1. These results strongly suggest that polyunsaturated n-6 fatty acids are able, via prostaglandin products, to regulate the CPT activity of certain tumour cells. This may have a considerable impact on mitochondrial beta-oxidation and cellular metabolism of fatty acids, reflected in the marked inhibition of cell proliferation by these fatty acids.
Biochem Mol Biol Int 1998 Jan
PMID:Regulation of tumour cell fatty acid oxidation by n-6 polyunsaturated fatty acids. 950 57

The role of dietary fatty acids in the regulation of carnitine palmitoyltransferase (CPT) activity has been shown in liver but their role in the regulation of tumour CPT activity in vivo is unknown. The present study investigated the effects of several oils, given as dietary supplements, upon the activity of CPT I and II in the Walker 256 rat tumour and the inhibition or stimulation of tumour growth. CPT I activity was markedly inhibited by soya oil, rich in linoleic acid (70% inhibition vs control). CPT I mRNA expression was not inhibited by any of the oils studied, indeed soya oil caused a marked increase (132% vs control) in expression. These results suggest that soya oil can modulate, in vivo, the beta-oxidative pathway of tumour tissue and further supports the hypothesis of tumour CPT I regulation by polyunsaturated fatty acids.
Biochem Mol Biol Int 1998 Jan
PMID:In vivo inhibition of Walker 256 tumour carnitine palmitoyltransferase I by soya oil dietary supplementation. 950 58

The syndrome of cancer cachexia is accompanied by several alterations of lipid metabolism, especially that in the liver. In this study we have investigated a possible mechanism whereby the presence of the Walker 256 carcinosarcoma affects hepatic fatty acid oxidative capacity in tumour-bearing rats. Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I), generally accepted as the main site of regulation of fatty acid oxidation, was unaffected by the presence of the extra-hepatic tumour. However, mitochondrial inner-membrane carnitine palmitoyltransferase II (CPT II) activity was markedly decreased in mitochondria isolated from the liver of tumour-bearing rats. Immuno-detection by Western blotting using a CPT II-specific antibody identified two bands (corresponding to M(r) 69,000 and 54,000) in tumour-bearing rats whereas only the normal-sized CPT II was present (at the expected M(r) 69,000) in mitochondria from control rats. It is suggested that the emergence of the second, smaller protein may represent a catalytically less active protein that arises in vivo, since its appearance was not affected by the inclusion of proteolysis inhibitors in the mitochondrial preparation buffers. Treatment of the tumour-bearing rats with indomethacin, a prostaglandin (including PGE2) synthesis inhibitor, increased CPT II activity to levels even higher than those found in the control animals. It is suggested that PGE2 may play a role in the control of CPT II expression in the liver of tumour-bearing rats. Indomethacin treatment did not affect either of the two CPT activities of the mitochondria isolated from tumour tissue.
Biochem Mol Biol Int 1998 Jan
PMID:Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: effect of indomethacin treatment. 950 62

Carnitine palmitoyltransferase-I (CPT-I) plays a crucial role in regulating cardiac fatty acid oxidation which provides the primary source of energy for cardiac muscle contraction. CPT-I catalyzes the transfer of long chain fatty acids into mitochondria and is recognized as the primary rate controlling step in fatty acid oxidation. Molecular cloning techniques have demonstrated that two CPT-I isoforms exist as genes encoding the 'muscle' and 'liver' enzymes. Regulation of fatty acid oxidation rates depends on both short-term regulation of enzyme activity and long-term regulation of enzyme synthesis. Most early investigations into metabolic control of fatty acid oxidation at the CPT-I step concentrated on the hepatic enzyme which can be inhibited by malonyl-CoA and can undergo dramatic amplification or reduction of its sensitivity to inhibition by malonyl-CoA. The muscle CPT-I is inherently more sensitive to malonyl-CoA inhibition but has not been found to undergo any alteration of its sensitivity. Short-term control of activity of muscle CPT-I is apparently regulated by malonyl-CoA concentration in response to fuel supply (glucose, lactate, pyruvate and ketone bodies). The liver isoform is the only CPT-I enzyme present in the mitochondria of liver, kidney, brain and most other tissues while muscle CPT-I is the sole isoform expressed in skeletal muscle as well as white and brown adipocytes. The heart is unique in that it contains both muscle and liver isoforms. Liver CPT-I is highly expressed in the fetal heart, but at birth its activity begins to decline whereas the muscle isoform, which is very low at birth, becomes the predominant enzyme during postnatal development. In this paper, the differential regulation of the two CPT-I isoforms at the protein and the gene level will be discussed.
Mol Cell Biochem 1998 Mar
PMID:Differential regulation in the heart of mitochondrial carnitine palmitoyltransferase-I muscle and liver isoforms. 954 27

In this work, an attempt was made to identify the reasons of impaired long-chain fatty acid utilization that was previously described in volume-overloaded rat hearts. The most significant data are the following: (1) The slowing down of long-chain fatty acid oxidation in severely hypertrophied hearts cannot be related to a feedback inhibition of carnitine palmitoyltransferase I from an excessive stimulation of glucose oxidation since, because of decreased tissue levels of L-carnitine, glucose oxidation also declines in volume-overloaded hearts. (2) While, in control hearts, the estimated intracellular concentrations of free carnitine are in the range of the respective Km of mitochondrial CPT I, a kinetic limitation of this enzyme could occur in hypertrophied hearts due to a 40% decrease in free carnitine. (3) The impaired palmitate oxidation persists upon the isolation of the mitochondria from these hearts even in presence of saturating concentrations of L-carnitine. In contrast, the rates of the conversion of both palmitoyl-CoA and palmitoylcarnitine into acetyl-CoA are unchanged. (4) The kinetic analyses of palmitoyl-CoA synthase and carnitine palmitoyltransferase I reactions do not reveal any differences between the two mitochondrial populations studied. On the other hand, the conversion of palmitate into palmitoylcarnitine proves to be substrate inhibited already at physiological concentrations of exogenous palmitate. The data presented in this work demonstrate that, during the development of severe cardiac hypertrophy, a fragilization of the mitochondrial outer membrane may occur. The functional integrity of this membrane seems to be further deteriorated by increasing concentrations of free fatty acids which gives rise to an impaired cooperation between palmitoyl-CoA synthase and carnitine palmitoyltransferase I. In intact myocardium, the utilization of the in situ generated palmitoyl-CoA can be further slowed down by decreased intracellular concentrations of free carnitine.
Mol Cell Biochem 1998 Mar
PMID:Palmitate oxidation by the mitochondria from volume-overloaded rat hearts. 954 38


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