The regulation of alanine and aspartate aminotransferase by different aminothiols and by vitamin B-6 derivatives.
We examined the effects on alanine aminotransferase and aspartate aminotransferase of different aminothiols (L-cysteine, D-cysteine, cysteamine, L-cysteine ethyl ester, L-cysteine methyl ester) and several vitamin B-6 derivatives (pyridoxal, pyridoxamine, pyridoxol, pyridoxol 5'-phosphate), before and after treatment with KOCN, which transforms these molecules into the corresponding carbamoyl derivatives. Only GPT, and not GOT, was specifically inhibited by L-cysteine and, to a lesser extent, by D-cysteine. The association reaction: PLP + apo GPT<-->holo GPT was inhibited by the vitamin B-6 derivatives, and this inhibition was prevented by pretreatment of the vitamin B-6 derivatives with KOCN. All the observed effects occurred at pH 7, 37 degrees C, at mM and even lower concentrations of reagents. Hence, they all potentially play a physiological role, in the regulation of the PLP dependent enzymes and of the vitamin B-6 levels in the cell.
Pagani
R
R
Istituto di Biochemica e di Enzimologia, Università di Siena, Italy.
Leoncini
R
R
Terzuoli
L
L
Pizzichini
M
M
Marinello
E
E
D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003485:Cyanates / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D011732:Pyridoxal Phosphate / Q000032:analysis / Q000494:pharmacology; D011733:Pyridoxamine / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D011736:Pyridoxine / Q000031:analogs & derivatives*; D013237:Stereoisomerism; D013696:Temperature
D003485:Cyanates; D011732:Pyridoxal Phosphate; D011733:Pyridoxamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C024835:potassium cyanate; D003545:Cysteine; D011736:Pyridoxine; C010627:pyridoxamine phosphate