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 carnitine palmitoyltransferase activity of various subcellular preparations measured with octanoyl-CoA as substrate was markedly increased by bovine serum albumin at low microM concentrations of octanoyl-CoA. However, even a large excess (500 microM) of this acyl-CoA did not inhibit the activity of the mitochondrial outer carnitine palmitoyltransferase, a carnitine palmitoyltransferase isoform that is particularly sensitive to inhibition by low microM concentrations of palmitoyl-CoA. This bovine serum albumin stimulation was independent of the salt activation of the carnitine palmitoyltransferase activity. The effects of acyl-CoA binding protein (ACBP) and the fatty acid binding protein were also examined with palmitoyl-CoA as substrate. The results were in line with the findings of stronger binding of acyl-CoA to ACBP but showed that fatty acid binding protein also binds acyl-CoA esters. Although the effects of these proteins on the outer mitochondrial carnitine palmitoyltransferase activity and its malonyl-CoA inhibition varied with the experimental conditions, they showed that the various carnitine palmitoyltransferase preparations are effectively able to use palmitoyl-CoA bound to ACBP in a near physiological molar ratio of 1:1 as well as that bound to the fatty acid binding protein. It is suggested that the three proteins mentioned above affect the carnitine palmitoyltransferase activities not only by binding of acyl-CoAs, preventing acyl-CoA inhibition, but also by facilitating the removal of the acylcarnitine product from carnitine palmitoyltransferase. These results support the possibility that the acyl-CoA binding ability of acyl-CoA binding protein and of fatty acid binding protein have a role in acyl-CoA metabolism in vivo.
Mol Cell Biochem 1994 Oct 26
PMID:Carnitine palmitoyltransferase activities: effects of serum albumin, acyl-CoA binding protein and fatty acid binding protein. 786 1

The maximal activity of the overt from of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.21) and its sensitivity to inhibition by malonyl CoA were measured in mitochondria prepared from the livers of rats which had been fed for 10 weeks on either a low fat diet (LF; 2.4% fat by weight) or on one of four high fat diets which contained 20% by weight of either hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO) or menhaden (fish) oil (MO). CPT I activity (i.e. activity per g of liver tissue), was elevated in animals fed the OO, SO or MO diets compared with those fed the LF or HCO diets. Feeding the HCO diet did not result in elevation of CPT I activity compared with feeding the LF diet. CPT I specific activity (i.e. activity per mg mitochondrial protein) was elevated in animals fed SO diet, but not in animals fed any of the other high fat diets. These observations suggest that an elevated fat load is not solely responsible for increasing CPT I activity, but that the fatty acid composition of the diet also plays a role. Hepatic CPT I activity of rats fed the LF diet was most sensitive to inhibition by malonyl CoA ([I50] = 0.53 microM). Each of the high fat diets decreased the sensitivity of CPT I to inhibition by malonyl CoA; CPT I activity in the livers from animals fed the MO diet was the least sensitive to malonyl CoA inhibition ([I50] = 1.8 microM). The fatty acid compositions of the major mitochondrial membrane phospholipids, phosphatidylcholine, phosphatidylethanolamine and cardiolipin were modified according to the fatty acid composition of the diet. Each of these phospholipids had a distinct fatty acid composition and similar effects of dietary lipid manipulation on the fatty acid compositions were observed. Feeding the SO diet resulted in fatty acid compositions which were most similar to those found after feeding the LF diet. Feeding the HCO and OO diets increased the proportions of stearic and oleic acids, respectively, while decreasing the proportion of linoeic acid. Feeding the MO diet resulted in increased proportions of palmitic, palmitoleic, eicosapentaenoic and docosahexaenoic acids and decreased proportions of linoleic and arachidonic acids in each of the phospholipids. It is proposed that the effects of dietary lipid manipulation upon CTP I activity and sensitivity to inhibition by malonyl CoA are due to alterations in the fatty acid composition of the phospholipids in the mitochondrial membrane where CPT I resides.
Biochem Mol Biol Int 1994 Oct
PMID:The effect of dietary lipid manipulation on hepatic mitochondrial phospholipid fatty acid composition and carnitine palmitoyltransferase I activity. 786 92

We recently noted the association of carnitine palmitoyltransferase (CPT) activity with a 54 kDa microsomal protein [Murthy and Pande (1993) Mol. Cell Biochem. 122, 133-138] that, based on amino-acid-sequence identity, seemed to be the protein previously described as a 'glucose-regulated protein-58' (GRP58), phosphoinositide-specific phospholipase C, hormone-induced protein-70, endoplasmic-reticulum protein-61 (ERp61), protein disulphide-isomerase, thiol protease, a protein affected in halothane anaesthesia and one that affects renal-tubular functions and the transcriptional activation of the interferon-alpha inducible genes. To ascertain the catalytic identity of this protein unambiguously, we have expressed the corresponding cDNA transiently and stably in human kidney 293 cells as well as in HeLa cells. In each case we found that expression led to an increase in assayable and immunoreactive 54 kDa CPT activity, whereas the protein disulphide-isomerase activity was not increased. In vitro expression in a cell-free transcription and translation system led to the synthesis of a approximately 57 kDa (precursor) protein that was processed to a approximately 54 kDa (mature) protein when microsomes were present; in both these experiments again a large increase in CPT activity was seen. Thus the present data provide compelling evidence that the 54 kDa protein in question is a CPT isoenzyme. It remains to be seen now how the ability of this protein to interconvert acyl-CoA and acylcarnitine would relate to the diverse functions indicated for this protein in vivo.
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PMID:A stress-regulated protein, GRP58, a member of thioredoxin superfamily, is a carnitine palmitoyltransferase isoenzyme. 799 51

Many studies have shown that L-carnitine has a positive effect on ischemic myocardium, probably by reducing accumulation of long-chain acyl coenzyme A (CoA) esters. Previous studies have involved whole-heart extracts and have not assessed changes of CoA ester levels in mitochondria, the site of translocase inhibition. To more precisely assess L-carnitine effects, we measured long-chain acyl CoA ester levels in cytosol and in mitochondria in the ischemic canine heart. Dogs were divided into four groups: a sham-operated control group; an untreated group; and high- and low-dose L-carnitine-treated groups (30 mg/kg and 100 mg/kg). After 60 min of ischemia, the heart was excised, and the cytosolic and mitochondrial fractions were isolated. CoA esters and the activity of carnitine palmitoylcarnitine transferase (CPT) I and II were measured in both compartments. Approximately 89% of cellular free CoA. 90% of cellular acetyl CoA, 97% of cellular shot-chain acyl CoA, and 92% of cellular long-chain acyl CoA were located in the mitochondrial space under the normal condition. Under the ischemic condition, mitochondrial free CoA was significantly decreased. Conversely, mitochondrial acetyl CoA and long-chain acyl CoA were significantly increased. Treatment with L-carnitine significantly decreased acetyl CoA and long-chain acyl CoA in the ischemic mitochondrial space in a dose-dependent manner. These results support the hypothesis that L-carnitine reduces accumulation of long-chain acyl CoA within the ischemic mitochondrial space and thereby improves mitochondrial function and adenine nucleotide translocation.
J Mol Cell Cardiol 1994 Apr
PMID:Effect of L-carnitine on mitochondrial acyl CoA esters in the ischemic dog heart. 807 6

To define metabolic influences on cardiac myosin expression and sarcoplasmic reticulum (SR) Ca(2+)-stimulated ATPase streptozotocin-diabetic rats were treated for 9-10 wk with etomoxir, an inhibitor of carnitine palmitoyl transferase I (CPT-1) and fatty acid synthesis, or an antilipolytic drug, acipimox. Etomoxir reduced myosin V3 of diabetic rats but did not normalize it. However, the high serum triglyceride, free-fatty acid and cholesterol concentrations in diabetic animals were greatly reduced. After bypassing the CPT-1 inhibition with a medium-chain fatty acid (miglyol) diet, the V3 contents and serum lipids were still reduced in the etomoxir-treated diabetic rats; V3 was also reduced in diabetic rats fed miglyol or treated with acipimox. Since low serum insulin or triiodothyronine concentrations in diabetic rats were not improved by these interventions but changes in V3 were correlated with those in triglyceride, free-fatty acid and cholesterol concentrations, it is likely that myosin may be influenced by some metabolic factors. To assess the role of adrenergic influences, diabetic rats (7-8 wk) were treated with an antisympathotonic drug, moxonidine, a beta-adrenoceptor blocking drug, propranolol, and a bradycardic drug, tedisamil. Myosin V3 was not reduced significantly in moxonidine-treated or propranolol-treated rats in comparison to untreated diabetic rats. Serum thyroid hormones and insulin were not altered, whereas triglycerides were reduced but not significantly by these antiadrenergic agents. Lowering serum lipids in diabetic rats by treatment with etomoxir, miglyol and acipimox increased the depressed SR Ca(2+)-stimulated ATPase activity. On the other hand, in diabetic rats treated with moxonidine, propranolol or tedisamil, the ATPase activity was not increased significantly. These results suggest that normalization of blood lipids is important for improving subcellular organelle function in diabetic hearts with impaired glucose utilization.
Mol Cell Biochem 1994 Mar 16
PMID:Modification of myosin isozymes and SR Ca(2+)-pump ATPase of the diabetic rat heart by lipid-lowering interventions. 807 10

A microsomal protein having N-terminal amino acid sequence SDVLELTDEN, was initially described as a phosphatidyl inositol-specific phospholipase C alpha when its cDNA was cloned (Bennett et al., Nature, 334, 268, 1988). Later, this protein, with an estimated molecular mass of 54 to 60 kDa, was shown to lack the phospholipase activity and instead a protein disulfide oxidoreductase and a thiol protease activities were ascribed to it. Following evidences indicated that the protein in question is the carnitine medium/long chain acyltransferase (CPT) of microsomes that was recently purified as a approximately 54 kDa protein (Murthy and Bieber, Protein Exp. Purif. 3, 75, 1992). First, the N-terminal amino acids of the microsomal CPT showed 100% homology to the sequence described above. Second, during purification of this CPT, the oxidoreductase and the thiol protease activities of the microsomes became separated from the CPT and these other activities were not found in the approximately 900 fold enriched CPT preparations. Third, an antibody to this protein did not immunoprecipitate oxidoreductase of the solubilized microsomal extract but precipitated the CPT. This same protein has been studied by others as the ERp61 (endoplasmic reticulum protein), GRP58 (glucose regulated protein), and HIP-70 (hormone induced protein) but its function was not identified.
Mol Cell Biochem 1993 May 26
PMID:Carnitine medium/long chain acyltransferase of microsomes seems to be the previously cloned approximately 54 kDa protein of unknown function. 823 44

The effects of CPT on the calf thymus Topoisomerase I-mediated DNA breakage-reunion reaction were studied at an enzyme concentration range proper for evidencing, at the same time, both DNA relaxation and DNA cleavage/religation. Some of the requirements and the optimal conditions for the formation and reversal of the CPT-trapped Topoisomerase I-DNA cleavable complex are also characterized. We conclude that: 1. Calf thymus (100 kDa) Topoisomerase I requires, for maximal DNA cleavage activity, specific and characteristic reaction conditions. 2. CPT does not affect these optimal conditions, but only stabilizes the normal enzyme-DNA intermediate. In this way, the drug lowers the religation process, becoming responsible for the relaxation inhibition. 3. The optimum of monovalent salt concentration for cleavable complex formation is found between 30 and 70 mM. These values are lower than those required for the relaxation activity optimum (75-125 mM NaCl). 4. The addition of 0.5 M monovalent salt causes reversal of the reaction, and shifts the equilibrium distribution between cleavable intermediate and closed relaxed DNA in the direction of DNA resealing. Therefore, it is suggested that salt affects the cleavage but not the religation reaction.
Mol Biol Rep 1993 Feb
PMID:Effect of CPT on the calf thymus Topoisomerase I-mediated DNA breakage-reunion reaction: optimal conditions for the formation and reversal of the CPT trapped Topoisomerase I cleavable complex. 838 92

The effect of incubation with the protein kinase C activator, 4 beta-phorbol 12,13-dibutyrate (beta-PDBu) on the electrophysiological responses to hypoxia and combined hypoxia and hypoglycemia was investigated in the rat hippocampal slice. Preincubation with beta-PDBu prevents adenosine-mediated inhibition of synaptic transmission under normoxic, normoglycemic conditions. beta-PDBu preincubation also reduces the adenosine-mediated hypoxia-induced depression of synaptic transmission revealing a substantial adenosine-independent hypoxia-induced depression of synaptic transmission. During combined hypoxia and hypoglycemia, slices preincubated in beta-PDBu display a significant shortening of the time of anoxic depolarization, an effect of beta-PDBu that is not mimicked by application of the adenosine antagonist cyclopentyltheophylline (8-CPT). It is concluded that the state of PKC activation may influence the electrophysiological responses to hypoxia and ischemia.
Mol Chem Neuropathol 1995 Sep
PMID:Phorbol ester alters the electrophysiological responses to hypoxia and ischemic-like conditions in the rat hippocampal slice. 858 22

In order to investigate the long-chain fatty acid oxidative capacity of tumour cells, carnitine palmitoyltransferase I (CPT I) and CPT II were selected for study because they are rate-limiting regulatory enzymes. Measurable activities of both CPT I and CPT II were detected in several human and rat tumour cell types and in mouse fibroblasts. The activities were comparable with those previously reported for rat liver CPT I and II, ranging from 1-3 nmoles/min/mg protein for both CPT I and II. Walker 256 tumour tissue also contained detectable CPT I and II activities, thereby demonstrating that tumour tissue in vivo also has the capacity for the processing of fatty acyl CoA's in the mitochondrion. The possible regulation of tumour CPT I and II was investigated using the hormone insulin, both in vitro and in vivo. Insulin was found to increase CPT II activity in the T24/83 human bladder tumour in vitro and in the Walker 256 rat tumour in vivo. The results suggest that insulin may exert some control over the activity of CPT II in certain types of tumour. In contrast, insulin was without effect on CPT I activity in any of the tumours studied, either in vitro or in vivo.
Biochem Mol Biol Int 1995 Nov
PMID:Human and rat tumour cells possess mitochondrial carnitine palmitoyltransferase I and II: effects of insulin. 858 32

This study investigated the effect of prostaglandin E2 derivative, enprostil, on the hepatic lipid metabolism of Japanese quail. In experiment 1, the birds received 0.1, 1, 10 or 100 micrograms enprostil/kg body weight intraperitoneally, and they were killed after 10, 30, 60 and 120 min. After 60 min, hepatic triacylglycerol content was reduced most effectively by 10 micrograms enprostil/kg body weight. In experiment 2, effect of enprostil (10 micrograms/kg body weight) on liver enzyme activities associated with lipid metabolism and plasma lipid concentrations was examined. There were no significant differences in malic enzyme and carnitine palmitoyltransferase activities. Peroxisomal beta-oxidation in birds which received enprostil was significantly lower than that in birds receiving the vehicle. Enprostil caused a significant decrease in plasma triacylglycerol and non-esterified fatty acid concentration. We conclude that the administration of enprostil reduces hepatic triacylglycerol content through the decreased influx of non-esterified fatty acid.
Biochem Mol Biol Int 1996 May
PMID:Prostaglandin E2 derivative, enprostil, reduces hepatic triacylglycerol content in Japanese quail. 879 60


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