Costanzo Endocrine Part 2

Front 1

Describe G proteins

Back 1

-Guanosine triphosphate (GTP) binding proteins that couple hormone receptors to adjacent effector molecules
-Has intrinsic GTPase activity

Front 2

What second messengers do G proteins have?

Back 2

-Adenylate cyclase
-Ca2+ calmodulin
-Inositol 1,4,5-triphosphaste (IP3)

Front 3

Describe the structure of G proteins

Back 3

-Have 3 subunits: α, β, and γ
-The α subunit can bind either GDP or GTP. When GDP is bound to the α subunit, the G protein in inactive. When GTP is bound, the G protein in active

Front 4

Describe the different kinds of G protein

Back 4

-G proteins can be either stimulatory (Gs) or inhibitory (Gi)
-Stimulatory or inhibitory activity resides in the α subunits, which are accordingly called αs or αi

Front 5

Describe the adenylate cyclase mechanism

Back 5

1. Hormone binds to a receptor in the cell membrane

2. GDP is released from the G protein and replaced by GTP
-Activates the G protein which then activates (Gs) or inhibits (Gi) adenylate cyclase.
-Intrinsic GTPase acitivty converts GTP back to GDP

3. Activates adenylate cyclase then catalyzes the conversion of ATP to cAMP

4. cAMP activates protein kinase A, which phosphorylates specific proteins, producing highly specific physiologic actions

5. cAMP is degraded to 5'-AMP by phosphodiesterase, which is inhibited by caffeine. Therefore, phosphodiesterase inhibitors would be expected to augment the physiologic actions of cAMP

Front 6

Describe the IP3 mechanism

Back 6

1. Hormone binds to a receptor in the cell membrane and, via a G protein, activates phospholipase C

2. Phospholipase C liberates diacylglycerol and IP3 from membrane lipids

3. IP3 mobilizes Ca2+ from the ER. Together, Ca2+ and diacylglycerol activate protein kinase C, which phosphorylates protein and causes specific physiologic actions

Front 7

Describe the Ca2+-calmodulin mechanism

Back 7

1. Hormone binds to a receptor in the cell membrane and, via a G protein, has two actions: it opens cell membrane Ca2+ channels and it releases Ca2+ from the ER.
-Together, these two actions produce an increase in intracellular [Ca2+]

2. Ca2+ binds to calmodulin, and the Ca2+ calmodulin complex produces physiologic actions

Front 8

Describe the steroid hormone and thyroid hormone mechanism

Back 8

1. Steroid (or thyroid) hormone diffuses across the cell membrane and binds to its receptor

2. The hormone-receptor complex enters the nucleus and dimerizes

3. The hormone-receptor dimers are transcription factors that bind to steroid-responsive elements (SREs) of DNA and initiate DNA transcription

4. New messenger RNA is produces, leaves the nucleus, and is translated to synthesize new proteins

5. The new proteins that are synthesized have specific physiologic actions.
-For example, 1,25-dihydroxycholecalcifeol induces the synthesis of calbindin D-28K, a Ca2+ binding protein in the intestine; aldosterone induces the synthesis of Na+ channels in the renal principle cells