Nitric oxide

Nitric oxide pathway, working backward. Step 2: IP3 is produced in the endothelial cell. What happened just before? Step 1: Acetylcholine bound muscarinic (G protein-coupled) receptors on the endothelial cell.

Nitric oxide pathway, working backward. Step 4: NO synthase is activated. What activated it, and where did that come from? Ca2+. It was released from the ER after IP3 opened the ER Ca2+ channels (step 3).

Nitric oxide pathway, working backward. Step 5: NO gas is made. Which enzyme made it, and from what? NO synthase (activated by Ca2+ in step 4), from the amino acid arginine.

Nitric oxide pathway, working backward. Step 6: Guanylyl cyclase is activated in the smooth muscle cell. What activated it, and how did it get there? Nitric oxide. It was made in the endothelial cell (step 5) and diffused into the neighboring smooth muscle cell.

Nitric oxide pathway, working backward. Step 7: cGMP is made. Which enzyme made it, and from what? Guanylyl cyclase (activated by NO in step 6), from GTP.

Nitric oxide pathway, working backward. Step 8: The smooth muscle relaxes. What caused it? cGMP, made by guanylyl cyclase in step 7.

Nitric oxide pathway, fill the gap. Step 2: IP3 is produced → ??? → Step 4: NO synthase is activated. What is the missing step? Step 3: IP3 opens Ca2+ channels on the ER, releasing Ca2+ into the cytoplasm.

Nitric oxide pathway, fill the gap. Step 5: NO is made from arginine → ??? → Step 7: GTP becomes cGMP. What is the missing step? Step 6: NO diffuses into the smooth muscle cell and activates guanylyl cyclase.

Nitric oxide pathway, fill the gap. Step 7: cGMP is made → ??? What is the final result? Step 8: cGMP promotes smooth muscle relaxation, so the vessel relaxes (dilates).

Nitric oxide pathway, cell check. Which steps happen in the endothelial cell and which in the smooth muscle cell? Endothelial cell: steps 1–5 (ACh binds → IP3 → Ca2+ → NO synthase → NO made). NO then crosses over. Smooth muscle cell: steps 6–8 (guanylyl cyclase → cGMP → relaxation).

Nitric oxide pathway: what is the one molecule that travels between the two cells, and why can it only reach neighboring cells? Nitric oxide (NO), a gas. It is quickly converted to nitrates and nitrites in the extracellular fluid, so it only reaches nearby cells (paracrine signaling).

Nitric oxide pathway, broken step. NO synthase is blocked (step 4 fails). What is the last step that still happens? Step 3. IP3 is made and Ca2+ is released in the endothelial cell, but no NO is made, so the smooth muscle never relaxes.

Nitric oxide pathway, broken step. Guanylyl cyclase is blocked (step 6 fails). Is NO still made? What is the last step that happens? Yes, NO is still made (step 5) and still reaches the smooth muscle, but no cGMP forms, so there is no relaxation.

Insulin pathway, working backward. Step 2: The insulin receptor phosphorylates itself. What happened just before? Step 1: Insulin bound the insulin receptor on the outside of the cell.

Insulin pathway, working backward. Step 3: Signaling proteins and transcription factors get phosphorylated. What phosphorylated them? The insulin receptor's own kinase domains, which were switched on when the receptor phosphorylated itself (step 2).

Insulin pathway, working backward. Step 4: GLUT4 vesicles move to the plasma membrane. What triggered this? Step 3: The phosphorylated receptor activated signaling proteins.

Insulin pathway, working backward. Step 5: Glucose enters the cell. What made this possible? Step 4: GLUT4 transporters were inserted into the plasma membrane when their vesicles fused with it.

Insulin pathway, fill the gap. Step 1: Insulin binds → ??? → Step 3: Signaling proteins are phosphorylated. What is the missing step? Step 2: The receptor's kinase domains phosphorylate the receptor itself (autophosphorylation).

Insulin pathway, fill the gap. Step 3: Signaling proteins are activated → ??? → Step 5: Glucose enters. What is the missing step? Step 4: GLUT4 vesicles move to and fuse with the plasma membrane, inserting GLUT4.

Insulin pathway, fill the gap. Steps 6–8: Transcription factors are activated → ??? What is the final step? Step 9: The transcription factors enter the nucleus and turn on transcription of DNA into mRNA (gene expression).

Insulin pathway, branch check. After step 3, the signal splits into which branches? 1) Glucose uptake: GLUT4 vesicles go to the membrane (steps 4–5). 2) Transcription factor goes directly to the nucleus (step 6). 3) Second messengers: PIP2 → IP3 + DAG → transcription factor (step 7). 4) Kinase cascade: MEK → MAPK → Erk → Elk (step 8). Branches 2–4 all end with gene expression (step 9).

Insulin pathway, timing check. Which steps are short-term effects and which are long-term? Short-term: steps 4–5 (GLUT4 to the membrane, glucose enters within minutes). Long-term: steps 6–9 (transcription factors change gene expression, which takes longer).

Insulin pathway, broken step. The receptor's kinase domain is dead (step 2 fails). What is the last step that still happens? Step 1. Insulin binds, but nothing gets phosphorylated, so there's no GLUT4 insertion, no glucose uptake, and no gene expression change.

Insulin pathway, broken step. GLUT4 vesicles can't fuse (step 4 fails). Which branches still work? The gene expression branches (steps 6–9) still work. Only glucose uptake (step 5) fails, because no GLUT4 reaches the membrane.

Insulin pathway, broken step. MEK is blocked. Which steps still happen? Steps 1–7 and the GLUT4 branch still work, so glucose is still taken up. Only the MEK → MAPK → Erk → Elk cascade (step 8) and the gene expression it drives fail.

Phosphoinositide pathway, working backward. Step 2: The G protein activates phospholipase C. What happened just before this? Step 1: Angiotensin II bound its G protein-coupled receptor on the vascular smooth muscle cell.

Phosphoinositide pathway, working backward. Step 3: PIP2 is cut into IP3 and DAG. What happened just before, and which enzyme did the cutting? Step 2: The G protein activated phospholipase C (PLC). PLC is the enzyme that cuts PIP2.

Phosphoinositide pathway, working backward. Step 4: Ca2+ channels on the smooth ER open. What opened them? IP3, made in step 3 when PLC cut PIP2. IP3 diffused through the cytoplasm to the ER.

Phosphoinositide pathway, working backward. Step 6: PKC becomes active. Which two things activated it, and where did each come from? DAG, which stayed in the membrane after PLC cut PIP2 (step 3), and Ca2+, which was released from the ER after IP3 opened its channels (steps 4–5).

Phosphoinositide pathway, working backward. Step 7: The blood vessel constricts. What caused it? Step 6: Protein kinase C (PKC) was activated by Ca2+ + DAG.

Phosphoinositide pathway, fill the gap. Step 3: PIP2 is cut into IP3 + DAG → ??? → Step 5: Ca2+ enters the cytoplasm. What is the missing step? Step 4: IP3 diffuses to the smooth ER and opens its Ca2+ channels.

Phosphoinositide pathway, fill the gap. Step 1: Angiotensin II binds its receptor → ??? → Step 3: PIP2 is cut into IP3 + DAG. What is the missing step? Step 2: The receptor activates a G protein, which activates phospholipase C.

Phosphoinositide pathway, fill the gap. Step 5: Ca2+ enters the cytoplasm → ??? → Step 7: Vasoconstriction. What is the missing step? Step 6: Ca2+ and DAG together activate protein kinase C (PKC).

Phosphoinositide pathway, location check. Where does each happen: the PLC cut, IP3's target, Ca2+ storage, DAG's location? The PLC cut happens in the plasma membrane. IP3 travels through the cytoplasm to the smooth ER. Ca2+ is stored in the ER lumen. DAG stays in the plasma membrane.

Phosphoinositide pathway, broken step. IP3 can't open the ER channel (step 4 fails). What is the last step that still happens? Step 3. PIP2 is still cut into IP3 + DAG, but Ca2+ is never released, so PKC isn't fully activated and there is no vasoconstriction.

Phosphoinositide pathway, broken step. PKC is missing (step 6 fails). What is the last step that still happens? Step 5. Ca2+ still floods the cytoplasm and DAG is in the membrane, but with no PKC there is no vasoconstriction.

Phosphoinositide pathway: which molecules are second messengers here? IP3, DAG, and Ca2+. All three are made or released inside the cell after angiotensin II (the first messenger) binds.