Deficiency of propionyl-CoA carboxylase and methylcrotonyl-CoA carboxylase in a patient with methylcrotonylglycinuria

The enzymes 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase were studied in fribroblasts derived from a patient with 3-methyl-crotonylglycinuria and from control individuals. There was a parallel defect in the activities of both enzymes in extracts of the cells of the patient. Supplementation with biotin of the medium in which the cells were grown restored the activity of both carboxylases to the normal range. Kinetic analysis of the activities of the carboxylases obtained from cells grown in biotin revealed K_M values for each enzyme that approximated normal. These data indicate that the primary defect in this patient is in the enzyme holocarboxylase synthetase which is responsible for activating biotin and transferring it to the apocarboxylase proteins.