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NBME 22 Answers

nbme22/Block 2/Question#22

A 35-year-old man comes to the physician because of ...

Adenylyl cyclase

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submitted by hayayah(603),

Growth hormone releasing hormone acts via G-coupled receptors. G coupled receptors need GTP to become activated and GTPase to become inactivated.

No GTP-ase --> chronically active growth hormone releasing hormone receptor --> constant activation of adenylyl cyclase / cAMP pathway and release of growth hormone.

mcl  This figure is useful https://ai2-s2-public.s3.amazonaws.com/figures/2017-08-08/a025a0e224d366e987bc15edd0f7764ef5611e0d/4-Figure3-1.png +  
mcl  [link](https://ai2-s2-public.s3.amazonaws.com/figures/2017-08-08/a025a0e224d366e987bc15edd0f7764ef5611e0d/4-Figure3-1.png) +  
meningitis  How did you knkow it was GHRH and not GH perse? +4  
meningitis  nevermind; I just read down below. Thank you +3  

The receptor in question is a G protein receptor on the pituitary mass. This would be the GHRH receptor. The GH receptor will be present downstream so that GH released from the pituitary can bind to it (these are JAK/STAT receptors). GHRH receptors are G¬s receptors. These receptors are bound at the alpha-subunit to GDP in the inactive state. When GHRH binds they activated when GTP attaches to the alpha-subunit instead. And thereby promotoes adenyl cyclase activity. GTPase is responsible to cleave this GTP from the alpha subunit to switch of the receptoe. Therefor a lack of GTPase activity will render he Gs receptor in a prolonged on state  Increased activity of Adenyl Cyclase.

osler_weber_rendu  Brilliant explanation +  

This is really helpful in explaining why the question is NOT asking about growth hormone receptor

+/- qfever(14),

Why is the answer adenylyl cyclase? I looked in FA and I saw that GH uses the JAK2/STAT pathway and that IGF-1 uses the MAP Kinase pathway. Not sure how adenylyl cyclase plays into this.

pug_sheen  I think they are talking about the GHRH receptor on somatotrophs, which works through the cAMP pathway. +  
staygoodpupper  I don’t know how it relates to GH/IGF-1 in particular, but the question said there was a mutation in the alpha subunit of Gs, which activates adenylyl cyclase. +3  
kash1f  I agree the patient does have Acromegaly, but in the question it talked about how the patient had a mutation that prevented the GTPase activity of Gas. So Gs would be overactive --> excess adenylyl cyclase +6  
hyperfukus  ugh i was so excited too bc i thought i remembered jak stat epicfail +