CEP wk1 - CELL COMMUNICATION Flashcards
3 TYPES OF CELL SIGNALLING
AUTOCRINE (targets sites on same cell) PARACRINE (targets sites on adjacent target cell) ENDOCRINE (hormones used to reach target cells)
1st vs 2nd messengers
first messengers go directly to receptor but secondary messengers are produced when a receptor is activated
OTTO LOEWI EXPERIMENT (to prove receptors)
2 separate frog hearts (stimulation of first heart released something that stimulated second heart contraction)
AGONIST V ANTAGONIST
agonist binds to a target & activates it but antagonist binds to target & prevents other molecules binding
NICOTINIC ACETYLCHOLINE RECEPTOR (nAcHR)
- pentamer (2 of the 5 sub-units are AcH binding site)
- no AcH = gate is shut so NA+ can’t cross membrane
HOW TO MEASURE LIGAND BINDING TO RECEPTOR
add radioactive ligand to sample containing receptor & allow to bind then wash away any excess ligand & measure radioactivity (proportional to ligand conc.)
HOW GPCR’S WORK (have 7 helices to have 1 central unit)
- agonist binds to receptor which stimulates heterotrimeric G protein (A,B,Y) to bind
- GDP in G-protein replaced with GTP (activates protein)
- activated G-protein A & B/Y sub-units split off & regulate effectors (B&Y anchored to membrane)
- G-alpha protein inactivated as GDP reformed (hydrolysed) & inactivated heterotrimeric G-protein reformed
ADENYL CYCLASE (ATP -> AMP)
- converts ATP to cAMP & then phosphodiesterase (PDE) converts cAMP -> AMP
PHOSPHOLIPASE C
- agonist binds to receptor & PIP2 split into DAG (activates protein kinase C) & InsP3 (provides calcium which binds to ion channels on ER surface to release CA2+ into membrane to activate protein kinase C (leads to effector)
- receptor = protein kinase C active = calcium binds to channels to release Ca2+ to membrane to also activate protein kinase
HORMONAL REGULATION OF GLYCOGEN
- glucagon binds to G-protein = adenyl cyclase= cAMP = AMP (by phosphodiesterase) = protein kinase A
- protein kinase A phosphorylates (activates) glycogen synthase (forms glycogen) & then forms p-glycogen synthase (inactive)
- protein kinase A also phosphorylates kinase (inactive) to glycogen phosphorylase B (inactive) which is activated to glycogen phosphorylase A (active)
- OVERALL glycogen + Pi = glucose
PROTEIN PHOSPHATASES
removes phosphates (phosphorylated protein -> protein)
TSH RECEPTOR ROLE IN THYROID
TSH released from pituitary = binds to GPCR = adenyl cyclase = cAMP = pKA (rep. of thyroid cells & induces release of thyroid hormones)
AUTONOMOUS THYROID ADENOMA (ATA)
benign tumour in thyroid = hyperthyroidism (mutation in TSH receptor so active in absence of TSH (makes cAMP = hormone release))
TSH RESISTANCE
mutation where TSH receptors resistant to TSH (hypothyroidism)
LIPOPHILIC HORMONES (STEROIDS)
pass through membrane without need of channels