Inhibition of P-enolpyruvate carboxykinase and of glyconeogenesis in Tetrahymena by 3-mercaptopicolinic acid.
Tetrahymena grown overnight in deep cultures were incubated for 1 hr with [1-14C]labeled substrates in the presence or absence of 3-mercaptopicolinic acid (3MPA). 3-MPA inhibited appearance of label in glycogen from bicarbonate, acetate, pentanoate, octanoate, and succinate, but not from glycerol or glucose. In vitro assays of phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase activity showed that both enzymes were about equally distributed between the particulate and cytosol fractions. 3-MPA inhibited phosphoenolpyruvate carboxykinase from both the cytoplasmic and particulate fractions, but had no effect on phosphoenolpyruvate carboxylase from either location. These results suggest that the in vivo effects of this drug are due to inhibition of glyconeogenesis at this site.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors*; D010848:Picolinic Acids / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013769:Tetrahymena pyriformis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D000085:Acetates; D001639:Bicarbonates; D010848:Picolinic Acids; D013438:Sulfhydryl Compounds; C008363:3-mercaptopicolinic acid; D006003:Glycogen; D002262:Carboxy-Lyases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose; D005990:Glycerol