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 decrease of steady-state transmembrane potential (delta psi) and loss of accumulated Ca2+ are magnified if palmitoyl-CoA is added to rat liver mitochondria exposed to Ca2+ and phosphate. The extent of this damage increases with increasing concentration of long-chain acyl-CoA. Addition of L-carnitine with or without the addition of palmitoyl-CoA considerably delays the deenergization. In the latter case, there is a substantial decrease in the assayed endogenous long-chain acyl-CoA content. This protective action of L-carnitine is abolished by L-aminocarnitine, a powerful inhibitor of carnitine palmitoyl transferase (palmitoyl-CoA: L-carnitine O-palmitoyltransferase, EC 2.3.1.21.). The removal of Ca2+ by EGTA, or the inhibition of its uptake by Ruthenium red or Mg2+ further enhances the degree of protection.
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PMID:Ca2+-mediated action of long-chain acyl-CoA on liver mitochondria energy-linked processes. 246 24

The carnitine palmitoyltransferase (CPT) activities of the outer and the inner membranes of rat liver mitochondria were markedly activated by increase in the ionic strength of the assay medium. ATP at physiological concentrations in the presence of Mg2+ effectively reversed the above effect with octanoyl-CoA, but not with palmitoyl-CoA, as a substrate. Other nucleotides were unable to substitute for ATP. This ATP-Mg2+ effect on the CPT activity was not seen with mitochondria of heart or of skeletal muscles. The remarkable nucleotide, substrate and tissue specificity of these effects indicate that the above phenomenon may be functional in vivo to regulate the ability of liver mitochondria to utilize medium chain fatty acids via the carnitine-dependent route.
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PMID:ATP-Mg2+ reversal of the salt activation of membrane bound carnitine palmitoyltransferase activities of liver mitochondria. 326 35

Methyl-2-tetradecylglycidic acid (MeTDGA) has been hypothesized to inhibit fatty acid oxidation by irreversible, active site-directed inactivation of carnitine palmitoyltransferase A after being converted to TDGA-CoA. Using synthetic TDGA-CoA, this hypothesis has been confirmed. Assessing enzyme inhibition in an isolated rat liver mitochondrial system, TDGA-CoA (synthetic or enzyme prepared) was more potent than TDGA or MeTDGA and retained activity in the absence of CoA or Mg2+-ATP. It inhibited palmitoyl-CoA but not palmitoyl carnitine oxidation. Enzyme inactivation was exponential, stereospecific, and fast (t0.5 = 38.5 s with 100 nM (R)-TDGA-CoA). TDGA-CoA was identified as a complexing type irreversible inhibitor (Ki approximately 0.27 microM) by the double reciprocal relationship between the pseudo-first order inactivation rate and its concentration, by the inverse dependence of the second order rate constant on its concentration, and by the independence of the first order rate from the enzyme concentration. Palmitoyl-CoA, CoA, and malonyl-CoA protected the enzyme, while L-carnitine and palmitoyl-L-carnitine were without effect. [3-14C] TDGA-CoA labeled a protein, Mr = 90,000, with a time course which paralleled that of enzyme inhibition; maximum specific binding was 16 pmol/mg of mitochondrial protein.
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PMID:Identification of 2-tetradecylglycidyl coenzyme A as the active form of methyl 2-tetradecylglycidate (methyl palmoxirate) and its characterization as an irreversible, active site-directed inhibitor of carnitine palmitoyltransferase A in isolated rat liver mitochondria. 654 20

1. Liver carnitine acyltransferase activities with palmitoyl-CoA and octanoyl-CoA as substrates and heart carnitine palmitoyltransferase were measured as overt activities in whole mitochondria or in mitochondria disrupted by sonication or detergent treatment. All measurements were made in sucrose/KCl-based media of 300 mosmol/litre. 2. In liver mitochondria, acyltransferase measured with octanoyl-CoA, like carnitine palmitoyltransferase, was found to have latent and overt activities. 3. Liver acyltransferase activities measured with octanoyl-CoA and palmitoyl-CoA differed in their response to changes in [K+], Triton X-100 treatment and, in particular, in their response to Mg2+. Mg2+ stimulated activity with octanoyl-CoA, but inhibited carnitine palmitoyltransferase. 4. The effects of K+ and Mg2+ on liver overt carnitine palmitoyltransferase activity were abolished by Triton X-100 treatment. 5. Heart overt carnitine palmitoyltransferase activity differed from the corresponding activity in liver in that it was more sensitive to changes in [K+] and was stimulated by Mg2+. Heart had less latent carnitine palmitoyltransferase activity than did liver. 6. Overt carnitine palmitoyltransferase in heart mitochondria was extremely sensitive to inhibition by malonyl-CoA. Triton X-100 abolished the effect of low concentrations of malonyl-CoA on this activity. 7. The inhibitory effect of malonyl-CoA on heart carnitine palmitoyltransferase could be overcome by increasing the concentration of palmitoyl-CoA.
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PMID:Carnitine acyltransferase activities in rat liver and heart measured with palmitoyl-CoA and octanoyl-CoA. Latency, effects of K+, bivalent metal ions and malonyl-CoA. 709 22

Cyclic AMP-mediated desensitization of D1 dopamine receptor-coupled adenylyl cyclase was investigated using NS20Y neuroblastoma cells. Pretreatment of the cells for 24 h with 8-(4-chlorophenylthio)-adenosine-3':5'-cyclic monophosphate (CPT-cAMP), a membrane-permeable analog of cAMP, resulted in an approximately 90% reduction of the maximum dopamine-stimulated adenylyl cyclase activity. In addition, there was a twofold reduction in the potency of dopamine for stimulating cAMP production that was not dependent on the concentration of Mg2+ in the assay. These effects of CPT-cAMP pretreatment were time dependent, showing a t1/2 of about 3 h and a maximum reduction after about 8 h. Receptor-binding activity, as measured using the D1-selective antagonist [3H]SCH-23390, also declined following CPT-cAMP pretreatment with a t1/2 of about 5 h and a maximum reduction of about 70% after 20 h. Saturation analysis indicated that the loss in radioligand binding was due to a reduction in maximum binding capacity (Bmax) with no alteration in receptor affinity (KD). The EC50 of CPT-cAMP for producing enzyme desensitization and D1 receptor downregulation was determined to be about 30 microM with a maximal response occurring at 1 mM. These regulatory effects of CPT-cAMP were pharmacologically specific as other analogs of cAMP, such as dibutryl-cAMP, 8-bromo-cAMP, and Sp-cAMPS, were capable of inducing D1 receptor desensitization and downregulation, whereas treatment of the cells with the cAMP antagonist Rp-cAMPS had no effect. Conversely, Rp-cAMPS was capable of blocking the regulatory effects of CPT-cAMP but was apparently without effect in blocking dopamine-induced desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic AMP-mediated desensitization of D1 dopamine receptor-coupled adenylyl cyclase in NS20Y neuroblastoma cells. 770 30

Effects of the cyclic AMP agonists 8-(4-chlorophenylthio)-adenosine 3':5' cyclic monophosphate (CPT-cAMP), dibutyryl cyclic AMP (dbcAMP) and forskolin were studied on extracellular field potentials in rat neocortex slices in vitro. CPT-cAMP and forskolin produced a prolonged enhancement of epileptiform activity resulting from removal of Mg2+ from the bathing medium. DbcAMP had no apparent effect except at high concentrations (1 mM), when it reduced bursting activity. Field potentials observed following electrical stimulation of the corpus callosum in the presence of Mg2+ were enhanced by CPT-cAMP and dbcAMP; however forskolin was without effect. Intracellular recording techniques demonstrated a transient excitatory influence of dbcAMP. The results indicate a role for cyclic AMP in seizure mechanisms.
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PMID:Cyclic AMP analogues increase excitability and enhance epileptiform activity in rat neocortex in vitro. 839 51

To characterize human skeletal muscle enzymatic adaptation to a low-carbohydrate, high-fat, and high-protein diet (LCD), subjects consumed a eucaloric diet consisting of 5% of the total energy intake from carbohydrate, 63% from fat, and 33% from protein for 6 days compared with their normal diet (52% carbohydrate, 33% fat, and 14% protein). Biopsies were taken from the vastus lateralis before and after 3 and 6 days on a LCD. Intact mitochondria were extracted from fresh muscle and analyzed for pyruvate dehydrogenase (PDH) kinase, total PDH, and carnitine palmitoyltransferase I activities and mitochondrial ATP production rate (using carbohydrate and fat substrates). beta-Hydroxyacyl CoA dehydrogenase, active PDH (PDHa), and citrate synthase activities were also measured on whole muscle homogenates. PDH kinase (PDHK) was calculated as the absolute value of the apparent first-order rate constant of the inactivation of PDH in the presence of 0.3 mM Mg2+-ATP. PDHK increased dramatically from 0.10 +/- 0.02 min-1 to 0.35 +/- 0.09 min-1 at 3 days and 0.49 +/- 0. 06 min-1 after 6 days. Resting PDHa activity decreased from 0.63 +/- 0.17 to 0.17 +/- 0.04 mmol. min-1. kg-1 after 6 days on the diet, whereas total PDH activity did not change. Activities for all other enzymes were unaltered by the LCD. In summary, severe deficiency of dietary carbohydrate combined with a twofold increase in dietary fat and protein caused a rapid three- to fivefold increase in PDHK activity in human skeletal muscle. The increased PDHK activity downregulated the amount of PDH in its active form at rest and decreased carbohydrate metabolism. However, an increase in the activities of enzymes involved in fatty acid oxidation did not occur.
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PMID:Human skeletal muscle pyruvate dehydrogenase kinase activity increases after a low-carbohydrate diet. 984 40

1. The actions of selective adenosine A1 and A2 receptor agonists were examined on synaptic currents in periaqueductal grey (PAG) neurons using patch-clamp recordings in brain slices. 2. The A1 receptor agonist 2-chloro-N-cyclopentyladenosine (CCPA), but not the A2 agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS21680), inhibited both electrically evoked inhibitory (eIPSCs) and excitatory (eEPSCs) postsynaptic currents. The actions of CCPA were reversed by the A1 receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). 3. In the absence or presence of forskolin, DPCPX had no effect on eIPSCs, suggesting that concentrations of tonically released adenosine are not sufficient to inhibit synaptic transmission in the PAG. 4. CCPA decreased the frequency of spontaneous miniature action potential-independent IPSCs (mIPSCs) but had no effect on their amplitude distributions. Inhibition persisted in nominally Ca2+-free, high Mg2+ solutions and in 4-aminopyridine. 5. The CCPA-induced decrease in mIPSC frequency was partially blocked by the non-selective protein kinase inhibitor staurosporine, the specific protein kinase A inhibitor 8-para-chlorophenylthioadenosine-3',5'-cyclic monophosphorothioate (Rp-8-CPT-cAMPS), and by 8-bromoadenosine cyclic 3',5' monophosphate (8-Br-cAMP). 6. These results suggest that A1 adenosine receptor agonists inhibit both GABAergic and glutamatergic synaptic transmission in the PAG. Inhibition of GABAergic transmission is mediated by presynaptic mechanisms that partly involve protein kinase A.
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PMID:Inhibition by adenosine receptor agonists of synaptic transmission in rat periaqueductal grey neurons. 1006 36

Male Sprague-Dawley rats were fed a cholesterol-free (Exp. 1) or cholesterol-supplemented (Exp. 2) diet containing 20% casein (control group) or 15% defatted squid and 5% casein (defatted squid group), as protein, for 14 d. Serum and hepatic cholesterol concentrations were lower in rats fed defatted squid than in those fed casein in both cholesterol-free (-20%, P < 0.05 and -15%, P < 0.05, respectively) and cholesterol-supplemented (-25%, P < 0.05 and -15%, P < 0.05, respectively) diets. Hepatic triglyceride concentration was lower in the defatted squid than in the control groups in both cholesterol-free (-51%, P< 0.05) and cholesterol-supplemented diets (-38%, P < 0.01). The activities of cytosolic fatty acid synthase and the NADPH-generating enzymes, malic enzyme and glucose-6-phosphate dehydrogenase, in the liver were lower in the defatted squid than in the control groups in both cholesterol-free (-21%, P< 0.01, -33%, P < 0.05, and -33%, P < 0.01, respectively) and cholesterol-supplemented diets (-34%, P < 0.05, -57%, P < 0.05, and -67%, P < 0.05, respectively). The activity of mitochondrial carnitine palmitoyltransferase in the liver was comparable between the control and defatted squid groups. The activity of Mg2+-dependent phosphatidate phosphohydrolase in the liver cytosol was lower in the defatted squid (-9%, P < 0.05) than in the control groups only in the cholesterol-free diet. Fecal excretion of total steroids was stimulated by the feeding of defatted squid in both cholesterol-free (+77%, P < 0.005) and cholesterol-supplemented diets (+29%, P < 0.01). These results suggest that the nonlipid fraction of squid exerts a hypocholesterolemic effect by increasing the excretion of total steroids in feces. The fraction also induces a triglyceride-lowering activity in the liver by decreasing hepatic lipogenesis.
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PMID:Effects of dietary defatted squid on cholesterol metabolism and hepatic lipogenesis in rats. 1143 57

Platelet activating factor (PAF), a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes. PAF can be produced by several renal cells under appropriate stimuli and it is thought to be implicated in renal diseases. The aim of this study is the characterization of DTT-insensitive cholinephosphotransferase (PAF-CPT) of human mesangial cell (HMC), the main regulatory enzyme of PAF de novo biosynthetic pathway. Microsomal fractions of mesangial cells were isolated and enzymatic activity and kinetic parameters were determined by TLC and in vitro biological test in rabbit washed platelets. The effect of bovine serum albumin (BSA), dithiothreitol (DTT), divalent cations (Mg2+ and Ca2+), EDTA, and various chemicals on the activity of PAF-CPT of HMC was also studied. Moreover, preliminary in vitro tests have been performed with several anti-inflammatory factors such as drugs (simvastatin, IFNa, rupatadine, tinzaparin, and salicylic acid) and bioactive compounds of Mediterranean diet (resveratrol and lipids of olive oil, olive pomace, sea bass "Dicentrarchus labrax," and gilthead sea bream "Sparus aurata"). The results indicated that the above compounds can influence PAF-CPT activity of HMC.
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PMID:Characterization of the de novo biosynthetic enzyme of platelet activating factor, DDT-insensitive cholinephosphotransferase, of human mesangial cells. 1771 Jan 9


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