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- W1824535382 abstract "Hydroxycobalamin[c-lactam] (HCCL) treatment in rats results in decreased hepatic L-methylmalonyl-CoA mutase activity and increased hepatic total CoA content. To test the hypothesis that HCCL increases hepatic CoA biosynthesis secondary to propionyl- and methylmalonyl-CoA accumulation. CoA homeostasis was studied in primary culture rat hepatocytes. Conversion of [14C]pantothenic acid to [14C]CoA in the primary culture system was accelerated to rates 3-5 times control by acute incubation with the acyl-CoA-generating carboxylic acids pivalate (10 mmol/L) or propionate (10 mmol/L). HCCL (1 mg/L included from 24 to 72 h of culture) had no affect on the distribution of the hepatocyte CoA pool or total CoA content. However, culture in the presence of HCCL and propionate (2 mmol/L) resulted in accumulation of methylmalonyl-CoA and a 59% increase in total CoA content. The combination of HCCL (1 mg/L) and propionate (0.5 mmol/L), but not HCCL alone, increased the rate of [14C]pantothenic acid conversion to [14C]CoA by 150%. Degradation of [14C]CoA in the primary culture hepatocyte system was unaffected by chronic exposure to 2 mmol/L propionate, but was increased 90% by the combination of HCCL and 2 mmol/L propionate. Thus, in the presence of a source of propionyl-CoA, HCCL treatment results in methylmalonyl-CoA accumulation and accelerated CoA biosynthesis. The increased CoA biosynthesis leads to increased hepatocyte total CoA content, which may contribute to cellular metabolic homeostasis under conditions of acyl-CoA accretion." @default.
- W1824535382 created "2016-06-24" @default.
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- W1824535382 date "1993-11-01" @default.
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- W1824535382 title "Hydroxycobalamin[c-lactam] Increases Total Coenzyme A Content in Primary Culture Hepatocytes by Accelerating Coenzyme A Biosynthesis Secondary to Acyl-CoA Accumulation" @default.
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- W1824535382 doi "https://doi.org/10.1093/jn/123.11.1801" @default.
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