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)

The theory of steady-state flux control was applied to characterize the regulation of beta-oxidation flux in uncoupled rat liver mitochondria oxidizing palmitoylcarnitine in the presence of rotenone, malonate and the beta-hydroxybutyrate/acetoacetate redox buffer. By titrations with inhibitors such as antimycin, myxothiazol, azide and 4-pentenoic acid, the flux control coefficients of the b-c1 complex, cytochrome c oxidase and thiolase, were determined experimentally. The flux control coefficients of carnitine palmitoyltransferase II, ETF:CoQ oxidoreductase and beta-hydroxybutyrate dehydrogenase were determined from elasticity coefficients obtained by measuring the flux dependencies of acyl-CoA and acetyl-CoA+CoASH concentrations, the electron transfer flavoprotein redox state, the CoQ redox state and the NAD redox state. It was found that at low flux rates the flux control was distributed mainly between acyl-CoA dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase (Ci = 0.89). At maximum flux rates, carnitine palmitoyltransferase II (Ci = 0.35) and thiolase (Ci = 0.13) contribute additionally to the flux control. Thus, the phenomena of regulation of mitochondrial beta-oxidation can be described as multistep control.
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PMID:Application of the theory of steady-state flux control to mitochondrial beta-oxidation. 166 35

The induction of peroxisome proliferation was examined in rat liver after administration of equal concentrations (1 mmol/kg body weight) of 1,10-bis(carboxymethylthiodecane) (BCMTD), 1-mono(carboxymethylthiotetradecane) (CMTTD), 1-mono(carboxymethylthiooctane) (CMTO), 1-mono(carboxyethylthiotetradecane) (CETTD), palmitic acid and hexadecanedioic acid (HDDA). BCMTD, a non-beta-oxidizable and non-omega-oxidizable sulphur-substituted fatty acid analogue was considerably more potent than CMTTD (only non-beta-oxidizable) in inducing enlargement of the liver and increasing peroxisomal activities (monitored by peroxisomal beta-oxidation, palmitoyl-CoA hydrolase and catalase activities). Morphometric analysis of randomly selected hepatocytes revealed that BCMTD and CMTTD treatment increased the number and size of peroxisomes and the relative volume fraction of the peroxisomes. All these cellular responses were more marked with BCMTD than compared with CMTTD. CMTO, a non-beta-oxidizable fatty acid analogue containing a lower hydrophobic alkyl-end than CMTTD and CETTD (a beta-oxidizable fatty acid analogue), showed a slight increase (1.4-1.8-fold) of peroxisomal beta-oxidation and caused marginally morphological changes of peroxisomes compared with CMTTD and BCMTD. The most striking effect of the alkylthiopropionic acid (CETTD) was an enhancement of the hepatic triacylglycerol level. Palmitic acid and hexadecanedioic acid only marginally affected the peroxisomal activities, but no morphological changes of peroxisomes and fat droplets were observed. The presented data strongly suggest that a minimal structural requirement for a peroxisome proliferator may be (1) a carboxylic acid group linked to (2) a hydrophobic backbone which (3) cannot be beta-oxidized i.e., the fatty acid analogues have a sulphur atom in the beta-position. It is also conceivable that blockage for omega-oxidation may potentiate the peroxisome-proliferating activities in as much as BCMTD was more potent than CMTTD. Two mitochondrial marker enzymes, carnitine palmitoyltransferase and succinate phenazine methosulphate oxidoreductase were differently affected after administration of the investigated compounds. Furthermore, BCMTD and CMTTD as well as HDDA treatments increased the number of mitochondria, but the mitochondria tended to be smaller. The overall results presented here indicate that the structural requirements for proliferation of mitochondria are not identical to those for proliferation of peroxisomes.
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PMID:Alkylthioacetic acid (3-thia fatty acids)--a new group of non-beta-oxidizable, peroxisome-inducing fatty acid analogues. I. A study on the structural requirements for proliferation of peroxisomes and mitochondria in rat liver. 275 28

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

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. Disulfide bond-forming oxidoreductase A-like protein (DsbA-L) is known to be a key molecule in protection against obesity and obesity-induced inflammation. In the present study, we used a modeling and simulation approach in an attempt to develop body mass index (BMI) and BMI-based NAFLD prediction models incorporating the DsbA-L polymorphism to predict the BMI and NAFLD in 341 elderly subjects. A nonlinear mixed-effect model best represented the sigmoidal relationship between the BMI and the logit function of the probability of NAFLD prevalence. The final models for BMI and NAFLD showed that DsbA-L rs1917760 polymorphism, age, and gender were associated with the BMI, whereas gender, patatin-like phospholipase 3 rs738409 polymorphism, HbA1c, and high-density and low-density lipoprotein cholesterol levels were associated with the risk of NAFLD. This information may aid in the genetic-based prevention of obesity and NAFLD in the general elderly population.
CPT Pharmacometrics Syst Pharmacol 2018 06
PMID:Modeling of the Weight Status and Risk of Nonalcoholic Fatty Liver Disease in Elderly Individuals: The Potential Impact of the Disulfide Bond-Forming Oxidoreductase A-Like Protein (DsbA-L) Polymorphism on the Weight Status. 2956 50

The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression. In free fatty acids-induced HepG2 cells, CPT dramatically decreased ROS content, increased mitochondrial NADH dehydrogenase (Complex I) and mitochondrial cytochrome C oxidase (Complex IV) levels. Furthermore, CPT could upregulate HO-1, quinine oxidoreductase 1 (NQO1) expression, and increase Nrf2 translocation from cytoplasm-to-nucleus. The results indicated CPT could protect mitochondria function and improve oxidative stress by activating Nrf2. Therefore, it can be inferred that CPT may be a potential agent against NAFLD.
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PMID:Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates non-alcoholic fatty liver disease via improving oxidative stress and mitochondrial dysfunction. 2977 90