Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver.
The relative roles of pyruvate kinase and malic enzyme in substrate cycling between pyruvate and oxaloacetate were examined in perfused livers of 24-hour-fasted normal and triiodothyronine (T3)-treated rats using an inhibitor of malic enzyme (hydroxymalonate). Livers were perfused for 60 minutes in a recirculating system with [3-13C]alanine (10 mmol/L, 99% 13C-enriched). The combined flux through pyruvate kinase plus malic enzyme relative to pyruvate carboxylase flux was assessed by the 13C-enrichment ratio of alanine C2 to glucose C5 in the perfusate, determined with 13C and 1H nuclear magnetic resonance (NMR) spectroscopy. In normal rat livers, the relative carbon flux through pyruvate kinase plus malic enzyme to pyruvate carboxylase was 0.18 +/- 0.04, and increased to 0.44 +/- 0.08 (P < .05) in the T3-treated group. After addition of hydroxymalonate, this relative carbon flux was unchanged in normal rat livers, but decreased to 0.15 +/- 0.04 (P < .01) in the T3-treated group, suggesting that the increased carbon flux in T3-treated livers was caused by increased flux through malic enzyme. Malic enzyme activity increased from 0.36 +/- 0.05 U/g liver in normal livers to 2.51 +/- 0.50 U/g liver (P < .05) in the T3-treated group, whereas there was no effect of T3 treatment on pyruvate kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000409:Alanine / Q000378:metabolism; D000818:Animals; D002244:Carbon / Q000378:metabolism; D002247:Carbon Isotopes; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008297:Male; D010071:Oxaloacetates / Q000378:metabolism; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013646:Tartronates / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*; D014316:Tritium
D002247:Carbon Isotopes; D010071:Oxaloacetates; D011773:Pyruvates; D013646:Tartronates; D014284:Triiodothyronine; D014316:Tritium; C032973:tartronic acid; D002244:Carbon; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating); D011766:Pyruvate Carboxylase; D005947:Glucose; D000409:Alanine