Metabolic studies on normal and pyruvate dehydrogenase deficient cultured human fibroblasts

Abstract

Secondary metabolic derangements may occur in cultured fibroblasts with a defined enzyme deficiency. The metabolism of cells deficient of pyruvate dehydrogenase (5% of normal) has been studied using radioactive labelled substrates. Compared to normal control cells the activity of glycolysis was 149% (P< 0.001), pentose phosphate shunt 144% (P<00.01), citric acid cycle 80% (P<0.002), and oxidation of acetate was 30% (P<0.01). The oxidation of palmitate and octanoate were not significantly different from that of control cells. Metabolic studies on fibroblasts may serve as a useful screening procedure for the detection of enzyme defects, but the results should be cautiously interpreted with respect to the localization of the primary defect.

Key Words:

• congenital lactic acidosis
• fatty acid metabolism
• glycolysis
• inborn error