5'-([(Z)-4-Amino-2-butenyl]methylamino)-5'-deoxyadenosine [Z)-AbeAdo) was tested in vitro and in vivo as a potential inhibitor of S-adenosyl-L-methionine decarboxylase (AdoMetDC), a pyruvoyl-containing enzyme, purified from rat liver. In vitro (Z)-AbeAdo produces a time- and dose-dependent irreversible inhibition of the enzyme. Saturation kinetics are observed when the enzyme is preincubated with (Z)-AbeAdo in the presence of 50 microM putrescine, a known activator of AdoMetDC. Under these conditions kinetic constants were measured (Ki = 0.56 +/- 0.04 microM; tau 1/2 = 0.51 +/- 0.03 min). The inhibition is not relieved by prolonged dialysis of the inactivated enzyme. The turnover number for (Z)-AbeAdo, i.e. the number of inactivator molecules required to inactivate one enzyme molecule, is approximately 1.5. The selectivity of (Z)-AbeAdo was explored: the compound is not a substrate of adenosine deaminase, mitochondrial monoamine oxidase and diamine oxidase, but is slowly oxidized by benzylamine oxidase from rat aorta. The (E)-isomer of AbeAdo, is at least 100-fold less active than (Z)-AbeAdo as a time-dependent inhibitor of rat liver AdoMetDC. In rats, intraperitoneal administration of (Z)-AbeAdo produces a rapid, long-lasting and dose-dependent decrease of AdoMetDC activity in ventral prostate, testis and brain.