TY - JOUR
T1 - Guanosine 5′, α-β-methylene, triphosphate, a novel GTP analog, causes persistent activation of adenylate cyclase
T2 - Evidence against pyrophosphorylation mechanism
AU - Spiegel, A. M.
AU - Downs, R. W.
AU - Aurbach, G. D.
PY - 1977/6/6
Y1 - 1977/6/6
N2 - To test the hypothesis that guanine nucleotides activate adenylate cyclase by a covalent mechanism involving pyrophosphorylation of the enzyme, we studied the effect of a novel GTP analog, guanosine 5′, α-β-methylene triphosphate (Gp(CH2)pp), with a methylene bond in the α-β-position that is stable to enzymatic hydrolysis. Gp(CH2)pp was as effective as GTP in stimulating rat reticulocyte adenylate cyclase in the presence of isoproterenol. Previously only guanine nucleotides with modified terminal phosphates such as guanylyl 5′-imidodiphosphate (Gpp(NH)p) were thought capable of causing persistent activation of adenylate cyclase. Gp(CH2)pp, however, caused persistent activation of rat reticulocyte and turkey erythrocyte adenylate cyclase. We conclude that guanine nucleotides do not activate adenylate cyclase by a pyrophosphorylation mechanism and that a modified γ-phosphate is not essential in guanine nucleotides for generation of the irreversibly-activated enzyme state.
AB - To test the hypothesis that guanine nucleotides activate adenylate cyclase by a covalent mechanism involving pyrophosphorylation of the enzyme, we studied the effect of a novel GTP analog, guanosine 5′, α-β-methylene triphosphate (Gp(CH2)pp), with a methylene bond in the α-β-position that is stable to enzymatic hydrolysis. Gp(CH2)pp was as effective as GTP in stimulating rat reticulocyte adenylate cyclase in the presence of isoproterenol. Previously only guanine nucleotides with modified terminal phosphates such as guanylyl 5′-imidodiphosphate (Gpp(NH)p) were thought capable of causing persistent activation of adenylate cyclase. Gp(CH2)pp, however, caused persistent activation of rat reticulocyte and turkey erythrocyte adenylate cyclase. We conclude that guanine nucleotides do not activate adenylate cyclase by a pyrophosphorylation mechanism and that a modified γ-phosphate is not essential in guanine nucleotides for generation of the irreversibly-activated enzyme state.
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U2 - 10.1016/0006-291X(77)91565-0
DO - 10.1016/0006-291X(77)91565-0
M3 - Article
C2 - 197925
AN - SCOPUS:0017408506
SN - 0006-291X
VL - 76
SP - 758
EP - 764
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -