BIO230H1 Lecture Notes - Lecture 4: Guanylyl Cyclase, Nitric Oxide Synthase, Cyclic Guanosine Monophosphate
Lecture Eight: Signaling Via Small Molecules
Signaling Via Small Molecules:
1. Independently of plasma membrane proteins
2. Through plasma membrane channels
3. Downstream of plasma membrane G-protein coupled receptors
Independently of Plasma Membrane Proteins:
• Molecules that can pass through the plasma membrane
via diffusion – does not require channel proteins
or receptors
o Hydrophobic molecules and H2O
Nitric Oxide (NO):
• Very small signaling molecule
• Made by the deamination of arginine by
NO synthases
• Acts locally due to a 5-10 second half
life (degrades very quickly)
• Affects smooth muscles and other target
cells
• Lumen of a blood vessel
(cavity)
o Surrounding the cavity are endothelial cells
which are a specialized type of epithelial cells
o Nerve interacts with both smooth muscle cells and endothelial cells
▪ Nerve terminal releases acetylcholine and it will bind to a receptor
▪ Receptor will activate NO synthase in endothelial cells
▪ NO synthase will deaminate arginine to make NO
• NO is small and hydrophobic – diffuses into plasma membrane
▪ NO will diffuse into the smooth muscle cells and will bind to guanylyl
cyclase
▪ Guanylyl cyclase will covert GTP into cyclic GMP which will relax the
smooth muscle cells
• This will cause the blood vessel to increase in diameter decreasing
blood pressure
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Other Small Hydrophobic Signaling Molecules:
• Steroid Hormones:
o Made from cholesterol
o Affect sexual characteristics and metabolism
• Thyroid Hormones:
o Made from tyrosine
o Increase metabolic rate
• Retinoid:
o Made form vitamin A
o Regulate development
• Vitamin D:
o Affects metabolism
The Nuclear Receptor Family:
• Contain binding sites for a small
hydrophobic molecule and for DNA
o Ligand binding region is near
the C-terminus
o Activation domain is near the
N-terminus to initiate transcription
• 48 identified in the human genome
• More than half only identified based
on sequence analyses:
o Their ligands are unknown
o They are known as orphan nuclear receptor
▪ When the ligand it binds to are unknown
but contain the same sequence
Ligand Binding:
• Alters receptor conformation
• Releases inhibitors
• Promote DNA binding and
downstream transcription
• Usually contains inhibitory
proteins on its C-terminus
• When bound to a ligand, it forms
a latch which releases the inhibitor
• The receptor will later bind to the DNA with its
DNA binding site and activate transcription
o It may require coactivator proteins
• Transported in extracellular fluid by carrier
proteins (since they are hydrophobic)
• Dissociate from carrier proteins upon cell entry
• In the cell they bind a member of the nuclear
receptor superfamily
o They go to the nucleus to work they don’t
initially go to the nucleus – some will start in
the cytosol
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find more resources at oneclass.com
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BIO230H1 Full Course Notes
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