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Flashcards in Biochem: Hormones Deck (28):
1

Gs
- pathway
- enzyme
- second messenger
- protein kinase
- examples

- 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

Cortisol is often released in response to chronic stress (often associated with an injury). How does it stimulate a cellular response?

- 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

Sequence of events leading from receptor to activation of a protein kinase via the cAMP and PIP2 2nd messenger system

1. hormone binds receptor
2. trimeric G protein in membrane is engaged
3. enzyme (adenylate cyclase of phospholipase)
4. 2nd messenger
5. protein kinase
6. protein phosphorylation (mins) and gene expression (hrs)

4

- caffeine is metabolized into _____ by _____
- _____ can prolong the half-life of caffeine
- caffeine makes ____ more potent

- caffeine is metabolized to theophylline by liver
- alcohol can prolong the half-life of caffeine
- caffeine makes epinephrine more potent

5

Gq
- pathway
- enzyme
- second messenger
- protein kinase
- examples

- 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

ANF

- 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

Gi
- pathway
- enzyme
- second messenger
- protein kinase
- examples

- 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

NO

- 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

monomeric p21 ras
- pathway
- enzyme
- second messenger
- protein kinase
- examples

- 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

E. coli heat stable toxin (STa)

- 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

Cholera toxin produces diarrhea by

- 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

- Where do you find insulin receptors?
- what is required for activation of tyrosine kinase activity?

- 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

How does Insulin control gene expression?

1. insulin binding activates tyrosine kinase activity
2. autophosphorylation of receptor
3. insulin receptor substrate (IRS) binds receptor and is phosphorylated on tyrosine residues
4. SH2-domain proteins bind phosphotyrosine residues on IRS

14

What enzyme cascades does the activating of tyrosine kinase by insulin activate?

1. activation of IP3 kinase, which increases translocation of GLUT-4 to the membrane in adipose and muscle
2. activation of protein phosphatase, which DEPHOSPHORYLATES enzymes
- (so activation of tyrosine kinase by insulin may lead to dephosphorylating enzymes)
3. stimulation of monomeric G protein p21ras encoded by the normal ras gene
- G-protein involved in cell growth, differentiation and survival

15

What if a patient takes sildenafil and NO at the same time?

BP will drop VERY quickly

16

What does the Pertussis toxin do?

- 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

the E. coli toxin produces traveler's diarrhea by

- 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

how do lipid soluble hormones interact with the cell?

- 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

- a protein kinase
- often works opposite (opposes) a

- phosphorylates
- protein phosphatase (dephosphorylates)

20

Water soluble Hormones

- 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

how does vasodilation occur in a runner?

- 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

Adenylate Cyclase

- plasma membrane-bound enzyme
- activated by ligand binding to Gs protein coupled receptor
- converts ATP --> cAMP and PPi
- cAMP activates PKA

23

heme oxygenase

- 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

NO synthase

- 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

phospholipase C

- 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

- Examples of things activated via Gs/Gi
- aka cAMP pathway

- glucagon
- epinephrine
- vasopressin (V2, ADH)

27

- examples of things activated via Gq
- aka PIP2 pathway

- vasopressin (V1, V3)
- vascular smooth muscles
- epinephrine

28

things activated via cGMP pathway

- Atrial natriuretic factor (ANF)
- NO