Mechanism of control of the turkey erythrocyte beta-adrenoceptor dependent adenylate cyclase by guanyl nucleotides: a minimum model.
Treatment of native turkey erythrocyte membranes with GMP and epinephrine produces a highly active but metastable form of adenylate cyclase which decays slowly to basal native state. The decay process is greatly facilitated by GTP and GDP beta S1, and is further enhanced by 1-epinephrine. This decay process is prevented reversibly by GMP. GppNHp, like GMP, prevents the decay process first reversibly, but with time stabilizes the highly active state in a persistently active state. The expression of the catalytic activity of the enzyme in the metastable state can also be inhibited reversibly by GTP, GDP beta S and GMP at all times during the decay process. The GppNHp stabilized form is not susceptible to nucleotide inhibition. Thus, two forms of the guanyl nucleotide unit are postulated to exist: an "open" and a "closed" form. In the presence of hormone and GTP, the enzyme shuttles between these two forms continuously. GMP and GppNHp favor the complete conversion to the "open" form in the presence of beta-agonist. Evidence is also presented for the existence of two GTP dependent processes which exhibit different apparent affinities towards the nucleotide: A high affinity GTP binding process is essential for the fruitful coupling between receptor and enzyme, and a low affinity GTPase site which is responsible for the termination of the hormonal signal.
D000262:Adenylyl Cyclases / Q000097:blood*; D000818:Animals; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006157:Guanosine Monophosphate / Q000494:pharmacology*; D007700:Kinetics; D008954:Models, Biological; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014422:Turkeys
D006150:Guanine Nucleotides; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D006157:Guanosine Monophosphate; D000262:Adenylyl Cyclases; D004837:Epinephrine