The antitumor drug, 1,3-bis(2-chloroethyl)-1-nitroso-urea, inactivates human nicotinamide mononucleotide adenylyltransferase.
Nicotinamide mononucleotide (NMN) adenylyltransferase (EC 2.7.7.1) from human placenta is rapidly inactivated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). A similar inactivation is observed with other C- and N-nitroso compounds. The inactivation by BCNU is dependent on incubation 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 BCNU inactivation and in preserving its catalytic properties, while ATP is less efficient. Incubation of BCNU-inactivated and dialysed NMN adenylyltransferase with dithiothreitol results in a partial recovery of the enzymatic activity.
Emanuelli
M
M
Istituto di Biochimica, Facoltà di Medicina e Chirurgia, Università di Ancona, Italy.
Raffaelli
N
N
Amici
A
A
Balducci
E
E
Natalini
P
P
Ruggieri
S
S
Magni
G
G
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002330:Carmustine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004229:Dithiothreitol; D006801:Humans; D009537:Nicotinamide Mononucleotide / Q000494:pharmacology; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000037:antagonists & inhibitors*; D010920:Placenta / Q000201:enzymology; D013696:Temperature; D013997:Time Factors
D009537:Nicotinamide Mononucleotide; D000255:Adenosine Triphosphate; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D004229:Dithiothreitol; D002330:Carmustine