Rate-limiting steps in metabolic pathways.
A method is proposed to detect whether a given enzyme catalyzes a rate-limiting step in a metabolic pathway. With the use of a range of concentrations of specific inhibitors of an enzyme, the finding of a biphasic response with an initial null effect indicates the non-rate-limiting nature of the enzyme. With this method, phosphoenolpyruvate carboxykinase is indicated to catalyze a rate-limiting step in lactate gluconeogenesis in hepatocytes from fasted rats.
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D003523:Cycloserine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005943:Gluconeogenesis / Q000187:drug effects*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D007773:Lactates; D008055:Lipids; D010848:Picolinic Acids; D013438:Sulfhydryl Compounds; D000625:Aminooxyacetic Acid; D003523:Cycloserine; D010729:Phosphoenolpyruvate Carboxykinase (GTP)