THE ANTITUMOR DRUG, 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA, INACTIVATESHUMAN NICOTINAMIDE MONONUCLEOTIDE ADENYLYLTRANSFERASE

Nicotinamide mononucleotide (NMN) adenylyltransferase (EC 2.7.7.1) fro m human placenta is rapidly inactivated by 1,3-bis(2-chloroethyl)-1-ni trosourea (BCNU). A similar inactivation is observed with other C- and N-nitroso compounds. The inactivation by BCNU is dependent on incubat ion time, temperature and BCNU concentration. Protective reagents for -SH groups, dithiothreitol and beta-mercaptoethanol, and the substrate NMN are very effective in protecting NMN adenylyltransferase from BCN U inactivation and in preserving its catalytic properties, while ATP i s less efficient. Incubation of BCNU-inactivated and dialysed NMN aden ylyltransferase with dithiothreitol results in a partial recovery of t he enzymatic activity.