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)

1. The activities of long-chain acyl-CoA synthetase (acid: CoA ligase (AMP-forming), EC 6.2.1.3) and the "outer" carnitine long-chain acyltransferase (palmitoyl-CoA: L-carnitine O-palmitoyltransferase, EC 2.3.1.21) have been estimated in intact brown adipose tissue mitochondria. The assay of both enzymes is based on a coupled reaction in which the intramitochondrial (matrix) CoASH is the final acyl acceptor and the oxidation-reduction state of the flavoproteins in the acyl-CoA dehydrogens pathway is used to determine the intramitochondrial level of acyl-CoA. 2. Using endogenous fatty acids as the substrate, the progress curve of acyl-CoA synthetase activity was in most mitochondrial preparations linear within the first 30 s. When initial rates were measured, the Km value for CoASH (2.4 micron) was lower than previously determined for the acyl-CoA synthetase in brown adipose tissue mitochondria as well as in mitochondria of other tissues. The pH activity curve indicates that the unprotonated form of the fatty acids represents the substrate of acyl-CoA synthetase, i.e. similar to the effect of pH on the binding of fatty acids to bovine serum albumin. 3. Experimental evidence is presented that at temperatures higher than the transition temperature of the acyl-CoA synthetase (i.e. Tt = 19 degrees C), this enzymic reaction is rate-limiting in the sequence of coupled reactions leading to beta-oxidation in the mitochondrial matrix. 4. The initial rate of the long-chain acyl-COA synthetase reaction was estimated to v = 119 +/- 16 nmol . min-1 . mg-1 protein (mean +/- S.D., n = 5) at an optimal concentration of palmitate which exceeds that of rat heart mitochondria by a factor of 10.
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PMID:Long-chain acyl-CoA synthetase and "outer" carnitine long-chain acyltransferase activities of intact brown adipose tissue mitochondria. 69 44

The activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy, however, the mechanism remains unclear. Rat models of cardiac hypertrophy were created with transaortic constriction (TAC) to investigate the mechanistic role of AMPK involved. RT-PCR and Western blot analyses indicated that hypertrophy marker genes ANP and beta-MHC expression were up-regulated in the myocardium of TAC rats. We also observed that the expressions of peroxisome proliferator-activated receptor-alpha (PPARalpha) and its target genes, carnitine palmitoyl transferase-capital I, Ukrainian (CPT-capital I, Ukrainian) and medium-chain acyl-COA dehydrogenases (MCAD), were down-regulated, and the fatty acid oxidation was decreased in TAC rats. Treatment of TAC animals with 5-aminoimidazole 1 carboxamide ribonucleoside (AICAR, 0.5 mg/g body wt), a specific activator of AMPK, inhibited cardiac hypertrophy in TAC and reversed PPARalpha, CPT-I and MCAD expression and fatty acid oxidation. Similar observations were made in hypertrophied cardiomyocytes induced by phenylephrine in vitro. Treatment of hypertrophied cardiomyocytes with Compound C, a specific AMPK inhibitor, showed an effect opposite to that of AICAR. The effect of AICAR on cardiac hypertrophy was blocked after PPARalpha was silenced by transfection of cardiomyocytes with PPARalpha-siRNA. Luciferase activity assay suggested that AICAR elevates PPARalpha transcriptional activity. These results indicate that AMPK plays an important role in the inhibition of cardiac hypertrophy by activating the PPARalpha signaling pathway.
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PMID:Adenosine monophosphate-activated protein kinase inhibits cardiac hypertrophy through reactivating peroxisome proliferator-activated receptor-alpha signaling pathway. 1969 96