BIOLOGY 2B03 Lecture Notes - Lecture 15: Pyruvic Acid, Glycogen Phosphorylase, Gtpase
9 Jun 2018
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Cell Signalling: G-Protein Coupled Receptors
G-Protein Coupled Receptors
GPCRs have common structure - 7 membrane spanning domain consisting of 7 transmembrane alpha helices •
looping through membrane of cell
this creates 4 extracellular segments (E1->E4) - fold in extracellular space to form signal-binding domain •
also create 4 cytoplasmic domains (C1->C4) - fold to form internal domain ◦
Ex. rhodopsins, mammalian nose, neurotransmitter receptors, etc. •
Adrenergic Stress Response
Signal: catecholamines: epinephrine, norepinephrine •
Receptor: GPCR •
Intracellular Transduction •
Effector enzyme: adenylyl cyclase ◦
Second messenger: cAMP ◦
Cellular response: release of stored energy - fight/flight response •
fast response: enzyme activation ◦
slow response: activation of transcription ◦
Adrenergic Receptors: Alpha2 and Beta
beta adrenergic receptors are stimulatory: •
liver and adipose cells: glycolysis and lipolysis ◦
heart muscle: increase contraction and blood supply to tissues ◦
smooth muscle cells of intestine: increase relaxation, save energy for major locomotory muscles ◦
alpha 2 adrenergic receptors are inhibitory: •
blood vessels of smooth muscle of intestine, skin kidney cause arteries to constrict and blood supply is ◦
reduced to periphery
net result: increased energy for rapid motion in response to stress or exercise •
Catecholamines
products of adrenal glands •
picture shows epinephrine/adrenaline molecule •
binds 2 types of GPCR (B and alpha 2) •
breakdown of stored energy ◦
glycogen in liver: glycolysis ‣
fatty acids in adipose tissue: lipolysis ‣
Membrane-Associated Proteins
G alphas = GTPase switch protein: •
ACTIVE when bound to GTP ◦
INACTIVE when bound to GDP ◦
activation of receptors •
binding of hormone induces conformation change in ◦
receptor
activated receptor binds to G alpha subunit ◦
binding induces conformational change in G alpha, bound GDP dissociates and is replaced by GTP, G alpha ◦
dissociates from G beta-gamma
activation of effector: adenylyl cyclase •
hormone dissociates from receptor, G alpha binds to effector, activating it ◦
GTPase is fast! ‣
hydrolysis of GTP to GDP causes G alpha to dissociate from effector and reassociate with G beta-gamma ◦
G-protein becomes inactive ‣
