Molecular Endocrinology Flashcards
What are amino acids called in proteins
Composition of amino acids (3)
Residues
Amine group, carboxyl group, R side chain
Amino acid derived hormones:
- Glycine vs Glutamic acid
- Catecholamine-based amino acides (Synthesis pathway?)
- Iodine-modified amino acids (Synthesis pathway?)
- Indolamine-type amino acid synthesis
Glycine: Neutral amino acid found in all tissues and can also act as neurotransmitter in spinal cord
Glutamic acid: Acidic amino acid that can be modified into GABA through the enzyme Glutamic Acid Decarboxylase (GAD)
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- Synthesized from modified amino acids produced in CNS
- Derived from tyrosine (aromatic amino acid) -> phenylalanine (also aromatic) -> dopa (catechol structure added) -> dopamine -> norepinephrine -> epinephrine
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- Tyrosine -> MIT (+1 iodine) -> DIT (+1 iodine) -> T4 (DIT + DIT)
- -> T3 (-1 iodine from outer aromatic ring)
- or -> Reverse T3 (-1 iodine from inner ring)
- Classified as peptide hormone but acts like a steroid
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- Tryptophan (has indol structure) > Serotonin -> Melatonin
Why do peptide signalling molecules encompass the largest class of distinct signalling molecules? (3)
- Encoded where?
- Prepropeptide/Preprohormone
- Signal peptide
- Propeptide
- Inactive fragment
- Peptide/Hormone
- Number of residues (varies from 2-100)
- Combos of amino acids in chain can vary (primary structure)
- Also varies in secondary, tertiary, and quaternary structures
— - Encoded by DNA on ribosomes of rough ER
— - Propeptide/prohormone + signal peptide
- Connects propeptide to ER
- Inactive peptide
- Inactive part of peptide that will be cleaved
- Mature or functional peptide
- Basic synthetic pathway for lipid derived signalling molecules
- Eicosanoid synthesis
- Steroid nucleus
- C18, C19, and C21 hormone examples (4)
Acetyl CoA -> Eicosanoids
- Acetyl CoA -> HMG CoA -> Retinoic acid
- HMG CoA -> Cholesterol -> no 22 - Hydroxycholestoerol -> Pregnenolone (makes steroids)
** Makes dimer ligand-receptor heteromeric complexes and all steroids are hydrophobic + can pass thru membranes to activate gene response elements
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- Precursor is arachidonic acid produced from diacyglycerol (DAG)
- Produces leukotrienes, prostacylin (PGI2), thromboxane (TXB2), prostaglandin E (PGE)
- Role in inflammation, blood clotting, immune responses
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- Steroid nucleus has 19 carbons in total and 4 carbon rings
- C18: Estrogen, C19: Androgen
- C21: Corticosteroids, progesterones
What receptor mechanism is good for:
- Amino acids, peptides, proteins, ions, eicosanoids, gases, photons
- Peptides, proteins
- Steroids, thyroid hormones
- Amino acids, modified amino acids, peptides
- G-protein coupled receptors
- Kinase-based receptors
- Nuclear receptors (transcription factors)
- Ion channels
G-protein coupled receptor:
- Characteristics (# of helices, # of extracellular and intracellular loops, 3 subunits)
- 5 classes of G proteins
- 7 transmembrane helices
- 3 extracellular loops
- 3 intracellular loops
- Alpha (Binds to GTP and hydrolyzes + acts on downstream effectors), and beta-gamma (binds to downstream effectors)
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Gi (Inhibitory), Gs (stimulatory) - Activates cyclic AMP to activate secondary messengers like PKA (hydrolyzes glycogen into glucose and free phosphate)
Gq
- Activates phospholipase (PLC) to activate secondary messengers like inositol triphosphate (IP3) and diacylglycerol (DAG) (interacts with calcium stores to release)
Also Giq, G12, Gih
Receptors marked by what for internalization?
2 outcomes for downregulation and receptor recycling
What directs traffic through the pathway?
AP2-clathrin
1) Recycled back to membrane
2) Sent ti lysosome for degradation
Rabphilin (Rab) proteins
Kinase receptors:
- Differences with G-protein coupled receptors (3)
- Mechanism (4 steps) + Specialty of tyrosine kinase receptors and Jak-Stat kinases
- Insulin receptor (tyrosine kinase receptor) 2 pathways m
- Has extracellular ligand binding domain
- Single transmembrane domain
- Intracellular domain that acts as a tyrosine kinase
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1) Ligand binds to ligand-binding domain
2) Conformational change in C-tail that interacts with ATP
3) Protein kinase activated by phosphorylation and fan now produce fx in the cell
4) Receptor releases its ligand for degradation and returns to inactive state OR is internalized for degradation
** Tyrosine kinase has two receptors that can phosphorylate each other
** Jak-Stat kinases phosphorylate on Jak protein w/ Stat protein
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1) MAPK cascade - Cell proliferation
2) Protein kinase B (PKB) - Stops cell growth
Serine/Threonine kinases:
- Receptor mechanism
- 2 receptors that aren’t tethered together until ligand binds
Genomic mechanism of activation by steroids (3)
- Difference when done w/ T3
1) Freely diffuse into cells (they’re not aqueous) and bind for cystolic or nuclear receptors
2) Form dimers w/ receptor and become ligand-activated transcription factor to drive gene transcription
3) Zinc fingers appear on dimer and bind to DNA
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- Forms heterodimers w/ retinoic acid receptor (RAR) or orphan retinoid X receptors (RXR)
