The effects of biotin deficiency on organic acid metabolism: increase in propionyl coenzyme A-related organic acids in biotin-deficient rats.

Volatile organic acid levels in plasma and tissues and nonvolatile organic acid levels in urine of biotin-deficient (BD) rats were measured and compared with other factors of biotin deficiency. Biotin levels and the activities of propionyl coenzyme A (CoA) carboxylase (PCC) in the livers of these rats were decreased, respectively, to 22% +/- 3% and 3.6% +/- 0.3% of the average values of pair-fed controls. Plasma concentrations of propionate were higher (15 to 223 micrograms/mL) than those of controls (5 to 7 micrograms/mL), whereas plasma levels of 3-methylcrotonate were only minimally increased as compared with those of controls. Concentrations of these volatile acids in the tissues were similarly increased, although those in brain showed less remarkable increases as compared with levels in other tissues. In the urine of BD rats, large amounts of organic acids derived from propionyl CoA, as well as those from 3-methylcrotonyl CoA, were excreted. Plasma propionate levels were not apparently related to the severity of clinical symptoms, biotin levels, or carboxylase activities, but were related to the amounts of urinary ketone bodies, lactate, and some of the organic acids derived from branched-chain amino acids, including those from propionyl CoA.