The hepatic adenylate cyclase system. I. Evidence for transition states and structural requirements for guanine nucleotide activation

Y. Salomon, M. C. Lin, C. Londos, M. Rendell, M. Rodbell

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Previous studies showed that guanine nucleotides, acting at a site termed the nucleotide regulatory site, are required for activation of hepatic adenylate cyclase, and that glucagon facilitates this process. This study shows that only guanine nucleotides containing triphosphate groups at the 5' position of ribose (or 3' deoxyribose) are capable of activating the enzyme. The terminal phosphate is not utilized in the activation process, since 5' guanylylimidodiphosphate [Gpp(NH)p] and 5' guanylyl methylenediphosphonate, analogues of guanosine triphosphate that are not utilized in transferase or hydrolase reactions, stimulate enzyme activity. The nucleotides bind in their free form at the regulatory site; chelation by magnesium ion shifts the apparent concentration dependence for activation by Gpp(NH)p. Guanosine diphosphate inhibits competitively Gpp(NH)p stimulated activity and inhibits basal activity and activities stimulated by glucagon.

Original languageEnglish
Pages (from-to)4239-4245
Number of pages7
JournalJournal of Biological Chemistry
Volume250
Issue number11
StatePublished - 1975
Externally publishedYes

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Guanylyl Imidodiphosphate
Guanine Nucleotides
Adenylyl Cyclases
Chemical activation
Glucagon
Liver
Nucleotides
Ribose
Guanosine
Diphosphates
Enzyme activity
Hydrolases
Enzymes
Transferases
Chelation
Guanosine Triphosphate
Magnesium
Phosphates
Ions

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

The hepatic adenylate cyclase system. I. Evidence for transition states and structural requirements for guanine nucleotide activation. / Salomon, Y.; Lin, M. C.; Londos, C.; Rendell, M.; Rodbell, M.

In: Journal of Biological Chemistry, Vol. 250, No. 11, 1975, p. 4239-4245.

Research output: Contribution to journalArticle

Salomon, Y. ; Lin, M. C. ; Londos, C. ; Rendell, M. ; Rodbell, M. / The hepatic adenylate cyclase system. I. Evidence for transition states and structural requirements for guanine nucleotide activation. In: Journal of Biological Chemistry. 1975 ; Vol. 250, No. 11. pp. 4239-4245.
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