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J Clin Invest. 1979 December; 64(6): 1695–1702. doi: 10.1172/JCI109632. | PMCID: PMC371324 |
Biotin-response Organicaciduria MULTIPLE CARBOXYLASE DEFECTS AND COMPLEMENTATION STUDIES WITH PROPIONICACIDEMIA IN CULTURED FIBROBLASTS M. Saunders, L. Sweetman, B. Robinson, K. Roth, R. Cohn, and R. A. Gravel The Research Institute, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada Department of Pediatrics, University of California, San Diego, La Jolla, California 92093 Division of Biochemical Development, Children's Hospital, Philadelphia, Pennsylvania 19104 Abstract Fibroblast cultures from two individuals with biotin-responsive organicacidemia were found to have a pleiotropic deficiency of propionyl-CoA carboxylase, β-methylcrotonyl-CoA carboxylase, and pyruvate carboxylase activities after growth in biotin limited culture medium, conditions which do not affect the carboxylase activities of normal cells. All three enzyme activities were restored to normal levels after transferring the mutant strains to biotin-rich medium. Both patients excreted abnormal levels of an array of metabolic intermediates, including β-methylcrotonate, β-hydroxyisovalerate, β-hydroxypropionate, and lactate, which reflect metabolic blocks at all three carboxylase sites. 14 mutants deficient in only propionyl-CoA carboxylase activity from patients with propionicacidemia and the two biotin-responsive strains were examined for complementation with seven previously mapped pcc mutants. No new pcc complementation groups were identified. Nine of the mutants were mapped to group pccA. The remaining 12 mutants mapped to pccBC or its B or C subgroups, confirming the complex nature of this group. The biotin-responsive mutants failed to complement each other but did complement mutants from all the pcc groups. Thus biotin-responsive organicacidemia is defined by a new complementation group, bio. The results obtained in this study suggest that the bio mutants have a defect of either biotin transport or a common holocarboxylase synthetase required for the biotin activation of all three mitochondrial carboxylases. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. Images in this article Click on the image to see a larger version. These references are in PubMed. This may not be the complete list of references from this article. - Wadlington WB, Kilroy A, Ando T, Sweetman L, Nyhan WL. Hyperglycinemia and propionyl coA carboxylase deficiency and episodic severe illness without consistent ketosis. J Pediatr. 1975 May;86(5):707–712. [PubMed]
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