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)

Treatment of rats with the vitamin B12 analogue hydroxy-cobalamin[c-lactam] (HCCL) impairs methylmalonyl-CoA mutase function and leads to methylmalonic aciduria due to intracellular accumulation of propionyl and methylmalonyl-CoA. Since accumulation of these acyl-CoAs disrupts normal cellular regulation, the present investigation characterized metabolism in hepatocytes and liver mitochondria from rats treated subcutaneously with HCCL or saline (control) by osmotic minipump. Consistent with decreased methylmalonyl-CoA mutase activity, 14CO2 production from 1-14C-propionate (1 mM) was decreased by 76% and 82% after 2-3 wk and 5-6 wk of HCCL treatment, respectively. In contrast, after 5-6 wk of HCCL treatment, 14CO2 production from 1-14C-pyruvate (10 mM) and 1-14C-palmitate (0.8 mM) were increased by 45% and 49%, respectively. In isolated liver mitochondria, state 3 oxidation rates were unchanged or decreased, and activities of the mitochondrial enzymes, citrate synthetase, succinate dehydrogenase, carnitine palmitoyltransferase, and glutamate dehydrogenase (expressed per milligram mitochondrial protein) were unaffected by HCCL treatment. In contrast, activities of the same enzymes were significantly increased in both liver homogenate (expressed per gram liver) and isolated hepatocytes (expressed per 10(6) cells) from HCCL-treated rats. The mitochondrial protein per gram liver, calculated on the basis of the recovery of the mitochondrial enzymes, increased by 39% in 5-6 wk HCCL-treated rats. Activities of lactate dehydrogenase, catalase, cyanide-insensitive palmitoyl-CoA oxidation, and arylsulfatase A in liver were not affected by HCCL treatment. Hepatic levels of mitochondrial mRNAs were elevated up to 10-fold in HCCL-treated animals as assessed by Northern blot analysis. Thus, HCCL treatment is associated with enhanced mitochondrial oxidative capacity and an increased mitochondrial protein content per gram liver. Increased mitochondrial oxidative capacity may be a compensatory mechanism in response to the metabolic insult induced by HCCL administration.
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PMID:Increased hepatic mitochondrial capacity in rats with hydroxy-cobalamin[c-lactam]-induced methylmalonic aciduria. 170 51

The intrinsic factors involved in the temperature-dependent impairment of neuronal activity in hippocampal CA2-CA1 regions were investigated using optical recording techniques. At 32 degrees C, stimulation of the Schaffer collaterals in the hippocampal CA2 region evoked depolarizing optical responses that spread toward the CA1 region. The optical response was characterized by fast and slow components that were mainly related to the presynaptic action potentials and excitatory postsynaptic response, respectively. The increase of the temperature to 38 degrees C was associated with a reversible depression of the neuronal activity in the hippocampal brain preparations. The depression of neuronal activity was irreversible when the temperature was increased to 40 degrees C. In the presence of 22 mM glucose, the depression of the neuronal activity at 38 degrees C was significantly attenuated. Pyruvate (22 mM), but not lactate (22 mM), also improved the depression of neuronal activity induced by the temperature increase. Adenosine (200 microM) strongly depressed the excitatory postsynaptic response, but not presynaptic action potentials. 8-Cyclopentyl-1,3-dimethylxanthine (8-CPT) (10 microM), an adenosine A1 receptor blocker, attenuated the adenosine-induced depression of the excitatory postsynaptic response. 8-CPT (10 microM) prevented the impairment of the excitatory postsynaptic response induced by the increase of the temperature to 38 degrees C. In contrast, the depression of presynaptic action potential at 38 degrees C was not prevented by 8-CPT (10 microM). N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and methylcobalamin (10 microM), a vitamin B12 analogue, attenuated the inhibition of pre- and postsynaptic activities induced by the increase of the temperature to 38 degrees C. Glibenclamide, a KATP channel blocker, did not protect neuronal activity from the effects of the increase of the temperature. These results suggest that the heat-induced depression of neuronal activity is mediated by multiple factors, such as impairment of energy metabolism and increase in extracellular adenosine and nitric oxide (NO) levels in hippocampal neurons.
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PMID:Intrinsic factors involved in the depression of neuronal activity induced by temperature increase in rat hippocampal neurons. 1183 Sep 30

Paclitaxel/carboplatin chemotherapy for cancer (TC therapy) exhibits neurotoxicity and causes peripheral neuropathy at a high frequency, which is difficult to cope with. In this study, we investigated the efficacy of Goshajinkigan, a traditional Japanese herbal medicine, for TC therapy-induced peripheral neuropathy. The subjects included in our study were patients with ovarian or endometrial cancer who underwent TC therapy and developed peripheral neuropathy. The patients were randomly divided into Group A, comprising of 14 patients (vitamin B12 treatment), and Group B, comprising of 15 patients (vitamin B12 + Goshajinkigan treatment). The observation period was 6 weeks following treatment initiation, and the evaluation items were as follows: i) the current perception threshold (CPT value) of the peripheral nerve, ii) visual analogue scale for numbness, iii) National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grade of neurotoxicity, and iv) a questionnaire on the subjective symptoms of peripheral neuropathy (functional assessment of cancer therapy-taxane). These were compared between the groups and no significant differences were noted in any item. However, CTCAE grade 3 neurotoxicity developed in 2 patients (14.3%) after 6 weeks of administration in Group A, whereas no neurotoxicity was observed in Group B. When the change in the frequency of abnormal CPT ratio at 6 weeks of administration from that before treatment was compared between the groups, the frequency of abnormal value was significantly lower in Group B than in Group A (p<0.05). This suggests that Goshajinkigan inhibits the progression of peripheral neuropathy.
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PMID:Objective evaluation of the alleviating effects of Goshajinkigan on peripheral neuropathy induced by paclitaxel/carboplatin therapy: A multicenter collaborative study. 2296 45

Our recent study indicates that maternal vitamin B12 and omega-3 fatty acid status influence plasma and erythrocyte fatty acid profile in dams. The present study examines the effects of prenatal and postnatal vitamin B12 and omega-3 fatty acid status on lipid metabolism in the offspring. Pregnant dams were divided into five groups: Control; Vitamin B12 deficient (BD); Vitamin B12 supplemented (BS); Vitamin B12 deficient group supplemented with omega-3 fatty acids (BDO); Vitamin B12 supplemented group with omega-3 fatty acids (BSO). The offspring were continued on the same diets till 3 month of age. Vitamin B12 deficiency increased cholesterol levels (p<0.01) but reduced docosahexaenoic acid (DHA) (p<0.05), liver mRNA levels of acetyl CoA carboxylase-1 (ACC-1) (p<0.05) and carnitine palmitoyltransferase-1 (CPT-1) (p<0.01) in the offspring. Omega-3 fatty acid supplementation to this group normalized cholesterol but not mRNA levels of ACC-1 and CPT-1. Vitamin B12 supplementation normalized the levels cholesterol to that of control but increased plasma triglyceride (p<0.01) and reduced liver mRNA levels of adiponectin, ACC-1, and CPT-1 (p<0.01 for all). Supplementation of both vitamin B12 and omega-3 fatty acid normalized triglyceride and mRNA levels of all the above genes. Prenatal and postnatal vitamin B12 and omega-3 fatty acids together play a crucial role in regulating the genes involved in lipid metabolism in adult offspring.
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PMID:Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats. 2600 65