Chapter 9 Flashcards
(26 cards)
What is a hormone?
alters the metabolism of the cell bearing the hormone-receptor complex
What is a autocrine hormone?
binds to receptor on the cell that produces them
What are paracine hormones?
Act on cell close to cell that secreted it
secreted into interstitial space, short half life
Ex. prostaglandins, neurotransmitters
What are telecrine hormones?
act on cell at a distant site from cell that secreted it
secreted into the bloodstream, longer half life
ex. endocrine and GI hormones
What are the two different classes of hormones?
Water soluble (hydrophilic) and lipid soluble (lipophilic, hydrophobic)
Describe water soluble hormones.
Describe lipid soluble hormones.
How do water-soluble hormones act?
affect metabolism and gene expression via second messenger systems that activate protein kinases
What are protein kinases?
enzymes that phosphorylate many other proteins to change their activity
What is the cAMP pathway?
Gs (Gi) –> adenyl cyclase –> cAMP–> protein kinase A
examples: glucagon, epinephrine (beta and alpha 2). vasopressin (V2, ADH), kidney
What is the PIP2 pathway?
Gq–>phospholipase C –> DAG, IP3, Ca2+ –> Protein Kinase C
examples: vasopressin (V1, V3), vascular smooth muscle, epinephrine (alpha 1)
What is the cGMP pathway?
No G-protein
Guanyl cyclase–>cGMP–>Protein kinase G
examples: atrial natriuretic factor (ANF), nitric oxide (NO)
What is the insulin, growht factor pathway?
monomeric p21ras–>tyrosine kinase activity of the receptor
example: insulin, insulin-like growth factor (IGF), platelet derived growth factor (PDGF), epidermal growth factor (EGF)
–recptor has intrinsic protein kinase activity
no second messenger is required for protein kinase activation
What does the activitation of protein kinases cause?
phophorylation of enzymes to rapidly increase or decrease their activity
phophorylation of gene regulatory proteins (ex. CREB) to control gene expression (many hours)
–result: add more enzymes to cell
–increase in number of enzymes means an increase in Vmax for the reaction
ex. CREB induces PEPCK gene
What reverses the action of protein kinases?
protein phosphatases
How does the G protein function?
receptors are coupled through trimetric G proteins in membrane
3 subunits: alpha, beta, gamma
inactive form: alpha subunit bound to GDP and in complex with beta and gamma subunits
when hormone binds to receptor, receptor activation and engages G protein
GDP is replaced with GTP, enabling alpha subunit to disociate from beta and gamma subunits
activated alpha alters activity of adenylate cyclase (alpha s activates enzyme, alpha i inhibits enzyme)
GTP in activate alpha subunit is dephosphorylated to GDP and alpha rebinds to beta and gamma so G protein inactive
What is the action of cAMP and PIP2?
hormone binds receptor
trimeric G protein in membrane is engaged
enzyme (adenyl cyclase or phospholipase)
second messenger
protein kinase
protein phosphorylation (minutes) and gene expression (hours)
ex. inhibition of AC via Gi is epinephrin inhibition (through binding to alpha adrenergic recpetor) of insulin release from beta cells of pancreas
What is the action of cGMP?
distension–> Atrial natriuretic facotr (ANF) produced in atrium –>ANF binds to ANF receptor in vascular SM and kidney–>receptor have guanylate cyclase activity–>relaxation of vascular SM and vasodilation and promotes sodium and water excretion in the kidney
vasodilators–>NO synthesized by vascular endothelium–>diffuse to vascular SM–>bind heme group of soluble guanylate cyclase and activates enzyme
ANF receptor and soluble guanylate cycalse are associated with same vascular smooth muscle cells
Why is cGMP unique from cAMP?
ANF receptor: instrinsic guanylate cyclase activity
no G protein required, no 7 helix membrane spanning domain
NO: no receptor of G protein required
How does E. coli heat stable toxin (STa) work?
binds to guanylate cyclase receptor in enterocytes
stimulates guanylate cyclase and increases cGMP
causes increased acitivty of CFTR and diarrhea
How does the insulin receptor work?
no trimeric G protein, enzyme or second messenger required to activate protein tyrosine kinase activity
hormone binds receptor
receptor tyrosine kinase (protein kinase) is activated (dimerizes)
protein phosphorylation (autophosphorylation and activation of other proteins)
- Insulin receptor substrate (IRS-1) binds receptor and is phosphorylated on tyrosine residues
- proteins with SH2 domains bin to phosphotyrosine residues on IRS-1 and become active
3a. activation of phosphatidylinositol-3-kinase (PI-3 kinase), increase GLUT 4 in membrane of adipose and muscle tissues
3b. activation of protein phosphatases; insulin stimulation via its Tyrosine kinase receptor may lead to dephosphorylating enzymes
3c. stimulation of monomeric G protein (p21ras) encoded by normal ras gene
Why is the p21ras G protein unique?
monomeric
What effect do bacterial toxins have on G proteins?
Vibrio cholera exotoxin ADP ribosylates Gs alpha–> increase in cAMP–>chloride secretion from intestinal mucosal cells–>diarrhea
E. coli toxin (heat labile or LT) ADP ribosylates Gs alpha–> increase in cAMP–>chloride secretion from intestinal mucosal cells–>diarrhea
Bordetella pertussis exotoxin ADP ribosylates Gi alpha–>reduce responsiveness to receptor –> increases cAMP
What is the action of lipid soluble hormones?
diffuse through cell membrane
bind to respective recpetors inside cell (usually hae DNA binding domain–Zn fingers)
interact with specific response elements in enhancer/silencer regions of genes
ex. cotisol recpetors binds to its response element in enhancer region of PEPCK gene
–increase amount of PEPCK in hepatocyte and increase capacity of gluconeogenesis
