CATALYSIS OF THE COVALENT BINDING OF 3-HYDROXYAMINO-1-METHYL-5H-PYRIDO[4,3-B]INDOLE TO DNA BY A L-PROLINE-DEPENDENT AND ADENOSINE TRIPHOSPHATE-DEPENDENT ENZYME IN RAT HEPATIC CYTOSOL

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (6) , 2495-2500
Abstract
An enzymatic mechanism involved in the activation of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-hydroxy-Trp-P-2), a mutagenic intermediate of a tryptophan pyrolysate, was studied in vitro. In hepatic cytosol supplemented with ATP and L-proline, N-hydroxy-Trp-P-2 was converted to a form which reacts readily with DNA. The enzyme responsible for the activation was partially purified and identified as prolyl tRNA synthetase as judged by their cofactor requirements inhibition by pyrophosphate or AMP and copurification of their activities. The prolyl tRNA-dependent covalent binding of N-hydroxy-Trp-P-2 to DNA of hepatic cytosol was highest in rats, followed by mice, hamsters, rabbits and guinea pigs in that order. The capacity for the binding of N-hdyroxy-Trp-P-2 was largely consistent with their prolyl tRNA synthetase activity. With regard to the ultimate form of N-hydroxy-Trp-P-2 for the covalent binding, a possible formation of N,O-prolyl-3-amino-1-methyl-5H-pyrido[4,3-b]indole was proposed.