Studies on the formation of lactate and pyruvate from glucose in cultured skin fibroblasts: implications for detection of respiratory chain defects.
We investigated the time course of the formation of lactate and pyruvate from glucose in cultured skin fibroblasts from controls, from a patient with a cytochrome c oxidase deficiency and from controls treated with inhibitors of the individual respiratory chain complexes. Fibroblasts from the patient and inhibitor treated fibroblasts produced more lactate and less pyruvate; this resulted in a significant increase in the lactate to pyruvate ratio, reflecting an increased cytosolic NADH/NAD+ redox state. We conclude that measurement of lactate and pyruvate production from glucose in cultured skin fibroblasts can be of value in the diagnosis of inherited diseases of the mitochondrial respiratory chain.
Wijburg
F A
FA
Department of Pediatrics, University Hospital, Amsterdam, The Netherlands.
Feller
N
N
Scholte
H R
HR
Przyrembel
H
H
Wanders
R J
RJ
D002478:Cells, Cultured; D002675:Child, Preschool; D030401:Cytochrome-c Oxidase Deficiency; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007773:Lactates / Q000096:biosynthesis*; D008661:Metabolism, Inborn Errors / Q000175:diagnosis*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D012402:Rotenone / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D007773:Lactates; D011773:Pyruvates; D012402:Rotenone; D019289:Pyruvic Acid; D003576:Electron Transport Complex IV; D005947:Glucose