NBME 22 Adenylyl cyclase (NBME Answers)

Retired NBME 22 Answers

nbme22/Block 2/Question#22 (reveal difficulty score)
A 35-year-old man comes to the physician ...
Adenylyl cyclase 🔍 / 📺 / 🌳 / 📖
tags: endo repeat

+12 upvote downvote
submitted by ∗osgoodschlatter10(41)

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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.

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osler_weber_rendu Brilliant explanation +1

skonys Is it less about GHRH having a IP3 secondary messanger or GH using JAK/STAT and more that we were supposed to recognize that Gas is a Gs coupled receptor and Gs works through Adenylyl Cyclase. GTP binds to Gs and must be dephosphorylates by a GTPase to be inacivated. Because the tumor cells lack this function, Gs stays phosphorylated and Adenylyl Cyclase continues to be activated? Im just confused on if knowing the secondary messanger systems even matter or if acromegaly is thrown in as a distractor from the information provided. +1

weirdmed51 GH doesn’t have IP3 messenger, it has cAMP +

weirdmed51 GHRH * (sorry) +

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

+/- qfever(67)

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submitted by ∗hayayah(1212)

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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.

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mcl This figure is useful https://ai2-s2-public.s3.amazonaws.com/figures/2017-08-08/a025a0e224d366e987bc15edd0f7764ef5611e0d/4-Figure3-1.png +1

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 +19

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submitted by goldenwakosu(7)

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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.

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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 +31

hyperfukus ugh i was so excited too bc i thought i remembered jak stat epicfail +3

skonys Doesn't GHRH act through an IP3 seconary messanger? +

xmen the tumor secretes GH. GH act via a JAK/STAT Pathway. But the GH secretion is stimulated via a GHRH through a Gs. This Gs in this tumor's cells is mutated and is permanently actif. so cAMP will increase. +1

weirdmed51 @skonys GHRH works via cAMP +

kcyanide101 GnRH is IP3 --- Remember GOAT HAG? GHRH is CAMP remember FLAT ChAMP +

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