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)

Proteolysis of intact mitochondria by Nagarse (subtilisin BPN') and papain resulted in limited loss of activity of the outer-membrane carnitine palmitoyltransferase, but much greater loss of sensitivity to inhibition by malonyl-CoA. In contrast with a previous report [Murthy & Pande (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 378-382], we found that trypsin had no effect on malonyl-CoA sensitivity. Even when 80% of activity was destroyed by trypsin, there was no difference in the malonyl-CoA sensitivity of the enzyme remaining. Trypsin caused release of the intermembrane-space enzyme adenylate kinase, indicating loss of integrity of the mitochondrial outer membrane, whereas Nagarse and papain caused no release of that enzyme. Citrate synthase was not released by any of the three proteinases, indicating no damage to the mitochondrial inner membrane. When we examined the effects of proteolysis on the inhibition of carnitine palmitoyltransferase by a wide variety of inhibitors having different mechanisms of inhibition, we found differential proteolytic effects that were specific for those inhibitors (malonyl-CoA and hydroxyphenylglyoxylate) that have their inhibitory potencies diminished by changes in physiological state. Both of those inhibitors protected carnitine palmitoyltransferase from the effects of proteolysis, but did not inhibit the proteinases directly. Inhibition by two other inhibitors (DL-2-bromopalmitoyl-CoA and N-benzyladriamycin 14-valerate) was not altered by proteinase treatment, even when most of the enzyme activity had been destroyed. Inhibition by glyburide, which is minimally affected by physiological state, was affected only to a slight extent at the highest concentration of trypsin tested. Proteolysis by Nagarse appeared to produce loss of co-operativity in malonyl-CoA inhibition. The effects of proteolysis are discussed and compared with changes in Ki occurring with changing physiological states.
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PMID:Proteinase treatment of intact hepatic mitochondria has differential effects on inhibition of carnitine palmitoyltransferase by different inhibitors. 155 74

To assess the etiology of influenza-associated encephalopathy(IAE), a surveillance effort was conducted during 2000-2005 in Japan. Over half of fatal and handicapped IAE patients exhibited a disorder of mitochondrial beta-oxidation and ATP generation evoked by the thermolabile phenotype of carnitine palmitoyltransferase II variations with transiently elevated serum acylcarnitine during high-grade fever. Model mice having impaired mitochondrial beta-oxidation exhibited significant accumulation of mini-plasmin and up-regulation of trypsin in the cerebral capillaries after infection with influenza A virus, resulting in the destruction of blood-brain barrier and increased brain vascular permeability. Trypsin up-regulation was also evident in the neuronal cells in the hippocampus, suggesting a severe neurologic complication of IAE.
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PMID:[Analysis of SNPs and enzymatic disorder in the patients of influenza-associated encephalopathy: disorder of fatty acid metabolism in mitochondria induced by high fever]. 1703 63