Interactions of propionate and carnitine metabolism in isolated rat hepatocytes.
Accumulation of propionate and its metabolic products propionyl-CoA and methylmalonyl CoA results in disruption of normal hepatic metabolism. Carnitine can partially restore normal cellular function in the presence of propionate. This beneficial effect of carnitine has been hypothesized to result from removal of propionyl groups in the form of propionylcarnitine. The present study was designed to elucidate the kinetics of propionylcarnitine formation in isolated rat hepatocytes, and the consequences of propionylcarnitine formation on propionate and carnitine metabolism. 14C-Propionate was converted to CO2, glucose, and propionylcarnitine in the hepatocyte system. Rates of CO2 production plateaued at propionate concentrations above 0.5 to 1.0 mmol/L, while in contrast, rates of glucose production declined as the propionate concentration was increased from 1.0 to 10.0 mmol/L. Increasing concentrations of carnitine up to 10.0 mmol/L resulted in increased production of propionylcarnitine. Despite formation of propionylcarnitine, propionate conversion to CO2 and glucose was unaffected by addition of carnitine. Thus, 10 mmol/L carnitine was able to increase total propionate metabolism (conversion to CO2, glucose and propionylcarnitine) by 40%. Hepatocyte metabolism of propionate was associated with a decrease in carnitine concentration and an increase in short chain acylcarnitines. This decrease in carnitine concentration was also seen in the presence of 150 mumol/L added carnitine, and was greater with propionate as a substrate as compared to butyrate. High performance liquid chromatography was used to permit specific quantification of propionylcarnitine. This technique confirmed that in the presence of propionate, propionylcarnitine was the major acylcarnitine generated and was responsible for the depletion of free carnitine from the system.(ABSTRACT TRUNCATED AT 250 WORDS)
D000108:Acetylcarnitine / Q000096:biosynthesis; D000818:Animals; D002245:Carbon Dioxide / Q000096:biosynthesis; D002331:Carnitine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000096:biosynthesis; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D011422:Propionates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011422:Propionates; D002245:Carbon Dioxide; C003223:propionylcarnitine; D000108:Acetylcarnitine; D005947:Glucose; D002331:Carnitine