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

---

Query: EC:2.3.1.21 (CPT)
4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of key enzymes in glycerolipid biosynthesis and fatty acid oxidation were compared using CoA esters of naturally occurring positional isomers of octadecatrienoic acids (18:3) as the substrates. The trienoic acids employed were 9,12,15-18:3 (alpha-18:3), 6,9,12-18:3 (gamma-18:3), and 5,9,12-18:3 (pinolenic acid which is a fatty acid contained in pine seed oil, po-18:3). The activities of microsomal glycerol 3-phosphate acyltransferase obtained with various 18:3 were only slightly lower than or comparable with those obtained with palmitic (16:0), oleic (18:1), and linoleic (18:2) acids. Mitochondrial glycerol 3-phosphate acyltransferase was exclusively specific for saturated fatty acyl-CoA. The activities of microsomal diacylglycerol acyltransferase measured with various polyunsaturated fatty acyl-CoAs were significantly lower than those obtained with 16:0- and 18:1-CoAs. Among the polyunsaturated fatty acids, gamma-18:3 gave the distinctly low activity. The Vmax values of the mitochondrial carnitine palmitoyltransferase I were significantly higher with alpha-18:3 and po-18:3 but not gamma-18:3, than with 16:0 and 18:2, while the apparent Km values were the same irrespective of the types of acyl-CoA used except for the distinctly low value obtained with gamma-18:3. The response to an inhibitor of the acyltransferase reaction, malonyl-CoA, was appreciably exaggerated with 18:2, alpha-18:3, and po-18:3 more than with 16:0 and 18:1. However, the response with gamma-18:3 was the same as with 16:0. Thus, some of glycerolipid biosynthesis and fatty acid oxidation enzymes could discriminate not only the differences in the degree of unsaturation of fatty acids but also the positional distribution of double bond among the naturally occurring 18:3 acids.
...
PMID:Octadecatrienoic acids as the substrates for the key enzymes in glycerolipid biosynthesis and fatty acid oxidation in rat liver. 747 92

The regulation of hepatic mitochondrial carnitine palmitoyltransferase-I (CPT-I) was studied in rats during starvation and insulin-dependent diabetes and in rat H4IIE cells. The Vmax. for CPT-I in hepatic mitochondrial outer membranes isolated from starved and diabetic rats increased 2- and 3-fold respectively over fed control values with no change in Km values for substrates. Regulation of malonyl-CoA sensitivity of CPT-I in isolated mitochondrial outer membranes was indicated by an 8-fold increase in Ki during starvation and by a 50-fold increase in Ki in the diabetic state. Peroxisomal and microsomal CPT also had decreased sensitivity to inhibition by malonyl-CoA during starvation. CPT-I mRNA abundance was 7.5 times greater in livers of 48-h-starved rats and 14.6 times greater in livers of insulin-dependent diabetic rats compared with livers of fed rats. In H4IIE cells, insulin increased CPT-I sensitivity to inhibition by malonyl-CoA in 4 h, and sensitivity continued to increase up to 24 h after insulin addition. CPT-I mRNA levels in H4IIE cells were decreased by insulin after 4 h and continued to decrease so that at 24 h there was a 10-fold difference. The half-life of CPT-I mRNA was 4 h in the presence of actinomycin D or with actinomycin D plus insulin. These results suggest that insulin regulates CPT-I by inhibiting transcription of the CPT-I gene.
...
PMID:Insulin regulates enzyme activity, malonyl-CoA sensitivity and mRNA abundance of hepatic carnitine palmitoyltransferase-I. 757 18

Conditions have been developed for the solubilization of hepatic microsomal carnitine acyltransferase activity in good yield, with excellent long-term stability and with retention of malonyl-CoA sensitivity. Solubilized microsomal carnitine acyltransferase activity can be separated into malonyl-CoA-sensitive and -insensitive activities either by gel filtration on Superdex 200 or by anion-exchange chromatography on Resource Q. On gel filtration the apparent molecular masses of the malonyl-CoA-sensitive and -insensitive activities are approx. 300 kDa and 60 kDa respectively. The malonyl-CoA-sensitive and -insensitive activities have different fatty-acyl-chain-length specificities and different stabilities in the detergent octyl glucoside. Together these findings indicate that the malonyl-CoA-sensitive and -insensitive activities are due to different enzymes. The malonyl-CoA sensitivity of the inhibitable enzyme is markedly increased on reconstitution into soybean L-alpha-lecithin liposomes, demonstrating that phospholipids play a crucial role in the inhibition by this metabolite. Evidence is also provided that the malonyl-CoA-sensitive microsomal carnitine acyltransferase is a different enzyme from the malonyl-CoA-sensitive carnitine palmitoyltransferase found in the mitochondrial outer membrane. The possible physiological role of the two microsomal acyltransferases is discussed.
...
PMID:Solubilization and separation of two distinct carnitine acyltransferases from hepatic microsomes: characterization of the malonyl-CoA-sensitive enzyme. 757 37

Studies of effects of 4-thia-substituted fatty acid analogues on rat liver lipid metabolism are described. With isolated hepatocytes tetradecylthiopropionate was shown to divert [1-14C]oleate from beta-oxidation into esterification, the total amount of [1-14C]oleate metabolized remaining unchanged. Tetradecylthiopropionyl-CoA was a good substrate for mitochondrial carnitine palmitoyltransferases I and II (EC 2.3.1.21), acyl-CoA oxidase (EC 1.3.3.6), for the microsomal (but not mitochondrial) glycerophosphate acyltransferase (EC 2.3.1.15), and for long-chain acyl-CoA dehydrogenase (EC 1.3.99.3). In isolated hepatocytes, its 4-thia-trans-2-enoic derivative, tetradecylthioacrylate, inhibits both beta-oxidation of, and incorporation of, [1-14C]oleate into lipids. In rat liver mitochondria tetradecylthiocrylate inhibited beta-oxidation. The degree of inhibition was not markedly increased by preincubation with tetradecylthioacrylate. Tetradecylthioacrylyl-CoA was a poor substrate for carnitine palmitoyltransferase I, and inhibited carnitine palmitoyltransferase II, microsomal glycerophosphate acyltransferase and acyl-CoA oxidase. It is concluded that the inhibitory effects of tetradecylthiopropionyl-CoA are expressed intramitochondrially, whereas primary sites of inhibition by tetradecylthioacrylyl-CoA are extramitochondrial.
...
PMID:Effects of tetradecylthiopropionic acid and tetradecylthioacrylic acid on rat liver lipid metabolism. 783 78

This study was designed to examine whether n-3 and n-6 polyunsaturated fatty acids at a very low dietary level (about 0.2%) would alter liver activities in respect to fatty acid oxidation. Obese Zucker rats were used because of their low level of fatty acid oxidation, which would make increases easier to detect. Zucker rats were fed diets containing different oil mixtures (5%, w/w) with the same ratio of n-6/n-3 fatty acids supplied either as fish oil or arachidonic acid concentrate. Decreased hepatic triacylglycerol levels were observed only with the diet containing fish oil. In mitochondrial outer membranes, which support carnitine palmitoyltransferase I activity, cholesterol content was similar for all diets, while the percentage of 22:6n-3 and 20:4n-6 in phospholipids was enhanced about by 6 and 3% with the diets containing fish oil and arachidonic acid, respectively. With the fish oil diet, the only difference found in activities related to fatty acid oxidation was the lower sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition. With the diet containing arachidonic acid, peroxisomal fatty acid oxidation and carnitine palmitoyltransferase I activity were markedly depressed. Compared with the control diet, the diets enriched in fish oil and in arachidonic acid gave rise to a higher specific activity of aryl-ester hydrolase in microsomal fractions. We suggest that slight changes in composition of n-3 or n-6 polyunsaturated fatty acids in mitochondrial outer membranes may alter carnitine palmitoyltransferase I activity.
...
PMID:Effect of dietary n-3 and n-6 polyunsaturated fatty acids on lipid-metabolizing enzymes in obese rat liver. 796 69

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.
...
PMID:A stress-regulated protein, GRP58, a member of thioredoxin superfamily, is a carnitine palmitoyltransferase isoenzyme. 799 51

A carnitine palmitoyltransferase (CPT), extracted from microsomes with octyl glucoside, was purified and characterized as a 54-kDa protein and was found to show no malonyl-CoA inhibition (Murthy, M. S. R., and Bieber, L. L. (1992) Protein Exp. Purif. 3, 75-79). We show here that the malonyl-CoA-sensitive CPT of microsomes associates with their membrane, whereas the above 54-kDa CPT is a soluble luminal protein. Western blot probing with antibody to the 54-kDa CPT was found to show a positive response with the soluble microsomal fraction but not with their membranes. 2-Tetradecylglycidyl-CoA inhibited the membrane-associated CPT activity irreversibly, whereas the inhibition of the soluble CPT was largely reversible. Exposure of microsomes to [3H]etomoxir, ATP, and CoA led to the labeling of a approximately 47-kDa peptide that associated with membranes, whereas no such peptide labeling was seen with the soluble microsomal fraction. These and other results show (a) that microsomes have malonyl-CoA-sensitive, as well as malonyl-CoA-insensitive, CPT activities, (b) that these two activities are due to distinct proteins, (c) that the malonyl-CoA-sensitive CPT of microsomes is a previously uncharacterized CPT isoform, and (d) that the [3H]etomoxir-labeled approximately 47-kDa peptide is a likely candidate for the microsomal malonyl-CoA-sensitive CPT or its regulatory subunit.
...
PMID:Malonyl-CoA-sensitive and -insensitive carnitine palmitoyltransferase activities of microsomes are due to different proteins. 803 71

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.
...
PMID:Carnitine medium/long chain acyltransferase of microsomes seems to be the previously cloned approximately 54 kDa protein of unknown function. 823 44

It is known that thyroid hormone enhances the biosynthesis of phosphatidylcholine in the lung. The purpose of the present study was to investigate the effects of thyroid hormone on the activity of cholinephosphotransferase, the terminal enzyme in the CDP-choline pathway, in guinea pig lung mitochondria and microsomes. Intramuscular injection of triiodothyronine (T3, 0.25-4 mg/kg body wt) stimulated the activities of both mitochondrial and microsomal enzymes in a dose-dependent manner. However, the stimulation was much more pronounced in the microsomes than in the mitochondria. The stimulatory effect of T3 was blocked by the intraperitoneal injection of both actinomycin D and cycloheximide in the microsomes, whereas in the mitochondria, the hormonal effect was blocked only by cycloheximide. Thus, it is suggested that T3 stimulates not only the nucleocytoplasmic system for the de novo synthesis of the enzyme, but possibly also the regulation of the transport of the synthesized protein into the mitochondria. Furthermore, administration of T3 produced an increase in the uptake and incorporation of [14C]choline into phospholipids of lung slices in vitro. However, this effect was blocked by intraperitoneal injection of both actinomycin D and cycloheximide. Thus, the change in CPT activity by T3 in mitochondria is not reflected by enhanced incorporation of choline into phosphatidylcholine.
...
PMID:Role of thyroid hormone in de novo synthesis of cholinephosphotransferase in guinea pig lung mitochondria and microsomes. 828 14

Long-chain carnitine acyltransferases are a family of enzymes found in mitochondria, peroxisomes, and endoplasmic reticulum that catalyze the exchange of carnitine for coenzyme A in the fatty acyl-CoA. Conversion of the fatty acyl-CoA to fatty acylcarnitine renders the fatty acid more permeable to the various cellular membranes. The mitochondrial carnitine palmitoyltransferases are considered important in the regulation of mitochondrial beta-oxidation of long-chain fatty acids. However, palmitoylcarnitine produced by peroxisomal carnitine octanoyltransferase or by microsomal carnitine palmitoyltransferase is not different from that produced by the mitochondrial enzyme. Therefore, for there to be control of fatty acid oxidation by the long-chain carnitine acyltransferases, there would have to be some mechanism to coordinately regulate these varied enzymes. The first system of regulation involves inhibition by malonyl-CoA, an intermediate in the synthesis of fatty acids. Malonyl-CoA inhibits long-chain carnitine acyltransferase activity by all three enzymes at similar concentrations in the physiological range. In addition, the mitochondrial and peroxisomal enzymes are known to be regulated at the level of mRNA transcription by a number of shared factors. Although the microsomal enzyme is less well studied, there does, indeed, appear to be a pattern of coordinate regulation for this system.
...
PMID:Regulation of the long-chain carnitine acyltransferases. 837 Apr 73


<< Previous 1 2 3 4 5 6 Next >>

---