Brain pyruvate carboxylase and the pathophysiology of biotin-dependent diseases.

Given the cerebellar symptomatology of biotin-dependent diseases and other lactic acidoses, we hypothesized that cerebellar pyruvate carboxylase activity might be differentially low or especially sensitive to cofactor deprivation. Accordingly, pyruvate carboxylase activity was measured in selected areas of normal and biotin-deficient rat brain. Control cerebellar hemisphere and vermis specific activities were identical, and slightly higher than cerebral and brainstem activities. In biotin-deficient rats, hepatic pyruvate carboxylase activity was 3% of control, whereas pyruvate carboxylase activities of all brain sections were 53 to 71% of control. Brain histology was normal. Cerebellar pyruvate carboxylase activity is therefore not distinctly low or labile and is in fact preferentially maintained despite severe cofactor deprivation.