IMP dehydrogenase: inhibition by the anti-leukemic drug, tiazofurin.
Leuk Res
; 13(2): 179-84, 1989.
Article
en En
| MEDLINE
| ID: mdl-2564451
ABSTRACT
Tiazofurin through its active metabolite thiazole-4-carboxamide adenine dinucleotide (TAD) inhibits IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis. IMP dehydrogenase activity in human leukemic cell extracts (33.4 +/- 0.1 nmol/h/mg protein) was increased 11-fold compared to normal leukocytes (3.1 +/- 0.5). Km values for IMP and NAD+ of leukemic IMP dehydrogenase were 22.7 and 44.0 microM, respectively. XMP inhibited competitively with IMP and noncompetitively with NAD+. NADH exerted mixed type inhibition with respect to both IMP and NAD+. The inhibitory pattern of TAD was quite similar to that of NADH; however, the affinity of TAD to leukemic IMP dehydrogenase (Ki = 0.1 microM) was three orders of magnitude higher than the natural product NADH (Ki = 150 microM). These results contribute to an understanding of the mechanism of action of tiazofurin in the treatment of leukemia.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ribavirina
/
Ribonucleósidos
/
Leucemia Mielógena Crónica BCR-ABL Positiva
/
Crisis Blástica
/
IMP Deshidrogenasa
/
Cetona Oxidorreductasas
/
Antineoplásicos
Límite:
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Leuk Res
Año:
1989
Tipo del documento:
Article