Evidence for two genetic complementation groups in pyruvate carboxylase-deficient human fibroblast cell lines

Gerald L. Feldman*, Barry Wolf

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

We have examined genetic complementation in pyruvate carboxylase deficiency by comparing the enzyme activity in polyethylene glycol-induced heterokaryons with that in unfused mixtures of fibroblasts from three affected children. Complementation, manifested as a three- to sevenfold increase in pyruvate carboxylase activity, was observed in fusions between a biotin-responsive multiple carboxylase (pyruvate carboxylase, propionyl CoA carboxylase, and β-methylcrotonyl CoA carboxylase) deficient fibroblast line and two other lines deficient only in pyruvate carboxylase activity. Kinetic analysis of complementing pyruvate carboxylase deficient lines, measured by the rate of restoration of enzyme activity as a function of time, revealed that maximum restoration was achieved within 10-24 hr after fusion. This profile is similar to those observed for fusions between the multiple carboxylase deficient line and two lines deficient in propionyl CoA carboxylase activity that are known to represent different gene mutations. Although the patients with pyruvate carboxylase deficiency had similar clinical findings, our studies indicate that pyruvate carboxylase deficiency is genetically heterogeneous, with at least two distinct, probably intergenic, complementation groups.

Original languageEnglish (US)
Pages (from-to)617-624
Number of pages8
JournalBiochemical Genetics
Volume18
Issue number5-6
DOIs
StatePublished - Jun 1 1980

Keywords

  • biotin-dependent enzymes
  • genetic complementation
  • pyruvate carboxylase
  • pyruvate carboxylase deficiency

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry
  • Molecular Biology
  • Genetics

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