Biochem: Hormones Flashcards
1
Q
Gs
- pathway
- enzyme
- second messenger
- protein kinase
- examples
A
- pathway: cAMP
- enzyme: Adenyl cyclase
- second messenger: cAmp
- protein kinase: Protein Kinase A
- PKA phosphorylates CREB (cAMP response element binding protein)
- CREB-P diffuses into nucleus and binds to CRE,
- which up regulates gene expression (takes hours)
- examples: glucagon, epinephrine (beta, alpha 2), vasopressin (V2, ADH), kidney
2
Q
Cortisol is often released in response to chronic stress (often associated with an injury). How does it stimulate a cellular response?
A
- cortisol is a lipid-soluble hormone and can diffuse through the cell membrane where it binds to its receptor inside the cell
- cortisol receptor binds to its response element in the enhancer region of the PEPCK gene
- by increasing the amount of PEPCK in the hepatocyte, cortisol can increase the capacity for gluconeogenesis
3
Q
Sequence of events leading from receptor to activation of a protein kinase via the cAMP and PIP2 2nd messenger system
A
- hormone binds receptor
- trimeric G protein in membrane is engaged
- enzyme (adenylate cyclase of phospholipase)
- 2nd messenger
- protein kinase
- protein phosphorylation (mins) and gene expression (hrs)
4
Q
- caffeine is metabolized into _____ by _____
- _____ can prolong the half-life of caffeine
- caffeine makes ____ more potent
A
- caffeine is metabolized to theophylline by liver
- alcohol can prolong the half-life of caffeine
- caffeine makes epinephrine more potent
5
Q
Gq
- pathway
- enzyme
- second messenger
- protein kinase
- examples
A
- pathway: PIP2
- enzyme: phospholipase C
- second messenger: DAG, IP3, Ca2+
- protein kinase: Protein Kinase C
- PKC can affect gene expression or
- PKC can activate protein kinases and phosphorylate enzymes (i.e. glycogenolysis in minutes)
- examples: vasopressin (V1, V3), vascular smooth muscle, epinephrine (alpha 1)
6
Q
ANF
A
- produced by cells in atrium of the heart in response to dissension
- binds to ANF receptor in vascular smooth muscle and in the kidney
- causes relaxation of vascular SM, resulting in vasodilation
- in the kidney it promotes Na and H20 excretion
- ANF receptor spans membrane and has intrinsic guanylate cyclase activity assoc with the cytoplasmic domain
- bc no G protein is required in the membrane, lacks the 7-helix membrane domain
- 2nd messenger = cGMP
7
Q
Gi
- pathway
- enzyme
- second messenger
- protein kinase
- examples
A
- pathway: cAMP
- enzyme: Adenyl cyclase
- second messenger: cAmp
- protein kinase: Protein Kinase A
- PKA phosphorylates CREB (cAMP response element binding protein)
- CREB-P diffuses into nucleus and binds to CRE,
- which up regulates gene expression (takes hours)
8
Q
NO
A
- synthesized by vascular endothelium in response to vasodilators
- diffuses into surrounding vascular SM, where it
- directly binds the heme group of soluble cytoplasmic guanylate cyclase, activating the enzyme
- no G protein required
- 2nd messenger = cGMP
9
Q
monomeric p21 ras
- pathway
- enzyme
- second messenger
- protein kinase
- examples
A
- pathway: insulin, growth factors
- protein kinase: tyrosine kinase activity of receptor
- examples: insulin, insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF)
10
Q
E. coli heat stable toxin (STa)
A
- target: similar guanylate cyclase receptor in enterocytes
- toxin binds to and stimulates guanylate cyclase, increasing cGMP
- causes increased activity of CFTR and diarrhea
- (heat) Labile like the Air (cAMP),
- (heat) Stable like the Ground (cGMP
11
Q
Cholera toxin produces diarrhea by
A
- vibrio cholerae exotoxin ADP-ribosylates Gs alpha, leading to an increase in cAMP and
- subsequently chloride secretion from intestinal mucosal cells
- causing the diarrhea of cholera
12
Q
- Where do you find insulin receptors?
- what is required for activation of tyrosine kinase activity?
A
- muscle, adipose and liver cells all have insulin receptors
- insulin binding activates the tyrosine kinase activity assoc with the cytoplasmic domain of its receptor
- No trimeric G protein, enzyme or 2nd messenger required to activate this protein Tyrosine Kinase activity:
1. hormone binds receptor
2. receptor tyrosine kinase (protein kinase) is activated
3. protein phosphorylation (autophosphorylation and activation of other proteins)
13
Q
How does Insulin control gene expression?
A
- insulin binding activates tyrosine kinase activity
- autophosphorylation of receptor
- insulin receptor substrate (IRS) binds receptor and is phosphorylated on tyrosine residues
- SH2-domain proteins bind phosphotyrosine residues on IRS
14
Q
What enzyme cascades does the activating of tyrosine kinase by insulin activate?
A
- activation of IP3 kinase, which increases translocation of GLUT-4 to the membrane in adipose and muscle
- activation of protein phosphatase, which DEPHOSPHORYLATES enzymes
- (so activation of tyrosine kinase by insulin may lead to dephosphorylating enzymes) - stimulation of monomeric G protein p21ras encoded by the normal ras gene
- G-protein involved in cell growth, differentiation and survival
15
Q
What if a patient takes sildenafil and NO at the same time?
A
BP will drop VERY quickly
16
Q
What does the Pertussis toxin do?
A
- bordetella pertussis exotoxin ADP-ribosylates Gi-alpha
- dramatically reducing its responsiveness to the receptor
- thus increasing cAMP
- causes persistent paroxysmal coughing symptomatic of pertussis (whooping cough)
17
Q
the E. coli toxin produces traveler’s diarrhea by
A
- caused by heat Labile toxin
- ADP-ribosylation of Gs alpha by the E. Coli toxin
- leads to an increase in cAMP and
- subsequently chloride secretion from intestinal mucosal cells results in traveler’s diarrhea
- (heat) Labile like the Air (cAMP),
- (heat) Stable like the Ground (cGMP
18
Q
how do lipid soluble hormones interact with the cell?
A
- diffuse through the cell membrane, where they bind to their respective receptors inside the cell
- receptors have a DNA-binding domain (usually Zn fingers)
- interact w specific response elements in enhancer (or possibly silencer) regions associated w certain genes
- control of gene expression requires hours
- Ex) steroids, calcitriol, thyroxines, retinoic acid
19
Q
- a protein kinase
- often works opposite (opposes) a
A
- phosphorylates
- protein phosphatase (dephosphorylates)
20
Q
Water soluble Hormones
A
- receptor in cell membrane
- 2nd messengers often involved, activate protein kinases
- protein phosphorylation to modify activity of enzymes (requires minutes)
- control of gene expression through proteins such as cAMP response element (CREB) binding protein requires hours
- ex) insulin, glucagon, catecholamines
21
Q
how does vasodilation occur in a runner?
A
- endothelial cells release NO –> diffuses to nearby smooth m cells –> activates gunnel cyclase –> increases cGMP –> activates protein kinase G –> dephosylation of myosin light chains (so they don’t interact with actin) –> relaxation –> vasodilation
- same MOA by which NO causes vasodilation of corpus cavernosum of penis –> erection
- other sources of NO: nitroprusside, nitroglycerine, isosorbide dinitrate; Arginine –> NO (via NO synthase)
22
Q
Adenylate Cyclase
A
- plasma membrane-bound enzyme
- activated by ligand binding to Gs protein coupled receptor
- converts ATP –> cAMP and PPi
- cAMP activates PKA
23
Q
heme oxygenase
A
- enzyme that initiates conversion of heme to bilirubin
- cleaves cyclic heme to linear biliverdin –> releasing free Fe and carbon monoxide (CO)
- biliverdin reductase converts biliverdin to bilirubin
24
Q
NO synthase
A
- synthesizes NO from arginine
- rxn requires NADPH and O2 as substrates and produces NO and citrulline
- 3 isoforms of NOS:
1. endothelial (eNOS) and 2. neuronal (nNOS) - these are constitutively expressed and respond to a rise in calcium
3. inducible (iNOS) - independent of calcium levels - iNOS is induced in response to bacterial infection.
- NO is also a neurotransmitterq
25
Q
phospholipase C
A
- cleaves PIP2 into DAG and IP3
- IP3 –> release of Ca2+ from ER
- DAG –> activates PKC
- this cascade of events is initiated by binding of ligand to Gq protein coupled receptor
26
Q
- Examples of things activated via Gs/Gi
- aka cAMP pathway
A
- glucagon
- epinephrine
- vasopressin (V2, ADH)
27
Q
- examples of things activated via Gq
- aka PIP2 pathway
A
- vasopressin (V1, V3)
- vascular smooth muscles
- epinephrine
28
Q
things activated via cGMP pathway
A
- Atrial natriuretic factor (ANF)
- NO
