Effect of carnitine on propionate metabolism in the vitamin B-12--deficient rat.
Acyl-CoA thioesters are generated during the oxidation of organic acids in mammalian systems. Vitamin B-12 deficiency is associated with decreased L-methylmalonyl-CoA mutase activity, and consequent accumulation of propionyl-CoA and methylmalonyl-CoA. The formation of propionylcarnitine from propionyl-CoA and carnitine provides an alternative pathway to remove propionyl-CoA from cells. Hepatocytes isolated from vitamin B-12--deficient rats metabolized propionate (1 mM) to CO2 and glucose at only 23% and 12%, respectively, of the rates observed in hepatocytes from control animals. In contrast, no difference was seen in rates of pyruvate metabolism by hepatocytes from control and vitamin B-12--deficient rats. Addition of carnitine (10 mM) to hepatocyte incubations increased the rate of propionylcarnitine formation 10- to 20-fold without altering conversion of propionate to CO2 or glucose. The rate of propionylcarnitine formation was not affected by vitamin B-12 deficiency. When carnitine (10 mM) was added, propionylcarnitine generation represented 65-71% of total propionate utilization in hepatocytes isolated from vitamin B-12--deficient rats. Gluconeogenesis from [1-14C]pyruvate was inhibited by 1 mM propionate in hepatocytes from vitamin B-12--deficient rats. No effect of 1 mM propionate on glucose formation from pyruvate was seen using hepatocytes from control rats. Intraperitoneal administration of L-carnitine resulted in a significant increase in urinary propionylcarnitine excretion from vitamin B-12--deficient rats, but not from control animals. The results demonstrate that exogenous carnitine can significantly enhance propionyl-group utilization via the formation of acylcarnitines under the conditions of impaired acyl-CoA metabolism associated with vitamin B-12 deficiency.
Brass
E P
EP
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Ruff
L J
LJ
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000494:pharmacology* / Q000652:urine; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011422:Propionates / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014806:Vitamin B 12 Deficiency / Q000378:metabolism*
D011422:Propionates; D011773:Pyruvates; C003223:propionylcarnitine; D005947:Glucose; D002331:Carnitine