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
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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
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3
Q

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

A
  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)
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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
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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)
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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
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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)
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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
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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)
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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
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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
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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)
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13
Q

How does Insulin control gene expression?

A
  1. insulin –> tyrosine kinase activity
  2. intrinsic kinase autophosphorylation of cytoplasmic side
  3. insulin receptor substrate (IRS) binds receptor and is phosphorylated on tyrosine residues
  4. SH2-domain proteins bind phosphotyrosine residues on IRS
  5. PI3K (Glut 4 insertion) Pathway and RAS/MAPk PW
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14
Q

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

A
  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
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15
Q

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

A

BP will drop VERY quickly

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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