Guanosine 5′, α-β-methylene, triphosphate, a novel GTP analog, causes persistent activation of adenylate cyclase

Evidence against pyrophosphorylation mechanism

Allen M. Spiegel, R. W. Downs, G. D. Aurbach

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)758-764
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume76
Issue number3
DOIs
StatePublished - Jun 6 1977
Externally publishedYes

Fingerprint

Guanosine
Guanosine Triphosphate
Adenylyl Cyclases
Guanine Nucleotides
Chemical activation
Guanylyl Imidodiphosphate
Reticulocytes
Rats
Phosphates
Enzymatic hydrolysis
Enzymes
Isoproterenol
Hydrolysis
Erythrocytes
triphosphoric acid

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "Guanosine 5′, α-β-methylene, triphosphate, a novel GTP analog, causes persistent activation of adenylate cyclase: Evidence against pyrophosphorylation mechanism",
abstract = "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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T2 - Evidence against pyrophosphorylation mechanism

AU - Spiegel, Allen 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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