BCHE 395-18 2014 Biosignaling II

Hydrolysis with gtp hydrolysis no h bonding change

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Unformatted text preview: leads to the acGvaGon of few adenylyl cyclase enzymes •  Every acGve adenylyl cyclase enzyme makes several cAMP molecules, thus acGvaGng several PKA enzymes •  These acGvate thousands of glycogen- degrading enzymes in the liver Gssue •  At the end, tens of thousands of glucose molecules are released to the bloodstream Signal AmplificaGon •  Why so complicated? •  By uGlizing a cascade, very small amounts of signal (epinephrine) can mobilize tens of thousands of glucose molecules •  Hormone signal amplified by several orders of magnitude TerminaGon of Response 1. [Epinephrine] drops below Kd à༎ receptor dissociaGon 2. 3. The cAMP dissociates and the regulatory subunit rebinds Self- InacGvaGon in G- protein Signaling •  Epinephrine is meant to be a short- acGng signal •  The organism must stop glucose synthesis if there is no more need to fight or flee •  4. Down- regulaGon of cAMP occurs by the hydrolysis of GTP in the α subunit of the G- protein RGSs = regulators of G protein signaling G Protein Regulatory Factors GEFs = guanosine nucleoGde- exchange factors •  G proteins frequently require ac6va6ng proteins (GAP, RGS) and exchange factors (GEF) for funcGon •  GAPs and GEFs are allosteric effectors •  AC is analogous to a GEF •  Receptor is analogous to a GAP GAPs = GTPase AcGvator Proteins GTP Hydrolysis •  G protein structure •  H- Bonds between γ- phosphate and Thr35, Gly60 •  GAP regulates GTP hydrolysis •  With GTP hydrolysis, no H- bonding, change in conformaGon Which groups are H- bonding? Hormonal RegulaGon of Blood Glucose High Blood [glucose]...
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