Evidence of hemin as an end product inhibitor of L-alanine: 4,5-dioxovalerate transaminase in rat liver mitochondria.
This study describes the in vitro and in vivo effect of hemin on L-alanine:4,5-dioxovalerate transaminase activity. Hemin was shown to be an inhibitor of the purified enzyme and this inhibition was proportional to the concentration of hemin. The examined kinetic data with hemin showed uncompetitive inhibition for both alanine and 4,5-dioxovalerate. An apparent Ki of 30 and 42 microM for hemin were obtained with both alanine and 4,5-dioxovalerate, respectively. Moreover, the enzyme activity in liver was considerably decreased after the intravenous hemin administration and such an inhibition is dose and time dependent. Furthermore, maximum inhibition of the enzyme was observed 30 min after hemin injection and 60% enzyme inhibition was achieved with a dose of 1.2 mg/kg body wt of rat. Thus is suggests the important role of this enzyme on heme biosynthesis.
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D000637:Transaminases / Q000378:metabolism*; D014631:Valerates / Q000494:pharmacology
D014631:Valerates; D006418:Heme; C007509:4,5-dioxovaleric acid; D006427:Hemin; D000637:Transaminases; C019687:aminolevulinate aminotransferase; D000409:Alanine