Biochemistry Flashcards

(51 cards)

1
Q

How do hydrophilic hormones trigger a cellular response?

A
  • cannot penetrate cell membrane - interact w/ receptor on cell surface
  • activate a second messenger inside the cell to trigger a response
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2
Q

What 2 types of receptors do hydrophilic hormones interact with? Example for each?

A
  • GPCR (Epi)

- RTK (insulin)

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3
Q

What is the half life of hydrophilic hormones?

A

very short (seconds to minutes)

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4
Q

How do hydrophobic hormones trigger a cellular response?

A
  • passively diffuse through plasma membrane
  • bind to a receptor; hormone receptor complex = transcription factor that can bind to HRE (hormone response element) on DNA
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5
Q

What 2 types of receptors do hydrophobic hormones interact with?

A
  • cytoplasmic: bind to hormone in cytoplasm and translocate to nucleus
  • nuclear receptors: already present in nucleus and bound to DNA
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6
Q

What is the half life of hydrophobic hormones?

A

long half lives (hours to days)

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7
Q

What does an inactive GPCR look like?

A

trimeric protein with alpha, beta, and gamma subunits bound together; GDP bound to alpha

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8
Q

What must be done to activate a GPCR? What mediates this?

A
  • GDP -> GTP on alpha subunit; mediated by guanine nucleotide exchange (GEF)
  • alpha subunit breaks off
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9
Q

What must be done to inactivate a GPCR? What mediates this?

A
  • GTP -> GDP via GTPase-activating protein (GAP)

- alpha subunit binds back to beta and gamma

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10
Q

What is the mechanism of each of the following GPCRs: Gs, Gi, Gq, Gt?

A
  • Gs: stimulates adenylate cyclase; increased cAMP
  • Gi: inhibits adenylate cyclase; cAMP not made
  • Gq: stimulates cGMP phosphodiesterase; decreases cGMP
  • Gt: activates phospholipase C; increase in intracellular Ca
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11
Q

Give an example of a hormone that binds to each of the GPCRs (Gs, Gi, Gq, and Gt) and each of their receptors

A
  • Gs: Epi (beta adrenergic); Histamine (H2)
  • Gi: Epi/NE (alpha adrenergic); Dopamine (D2)
  • Gq: ACh (M3)
  • Gt: light (rhodopsin)
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12
Q

Describe the general structure of insulin. Storage form vs active form?

A
  • A and B chains linked by disulfide bridges
  • Storage form: hexamer (w/ zinc in the center)
  • Active form: monomer
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13
Q

Describe the steps of insulin synthesis (3)

A

Preproinsulin mRNA translated to preproinsulin (ribosome) -> forms proinsulin in ER lumen) -> folded and transported to Golgi -> forms insulin

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14
Q

Describe the 2 phases of insulin secretion

A
  • 1st phase: rapid and granules come from readily releasable pool (RRP)
  • 2nd phase: sustained; comes from larger reserve pool
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15
Q

What type of receptor does insulin bind to? What does this cause?

A

binds to RTK (alpha extracellular subunit); causes phosphorylation of tyrosine on beta intracellular subunit

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16
Q

Insulin signaling: what binds to phosphotyrosine in the RAS dependent pathway?

A

insulin receptor substrate 1 (IRS-1) -> becomes phosphorylated

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17
Q

Insulin signaling: what binds to phosphorylated IRS-1 in the RAS dependent pathway? What does this initiate?

A

binds to GRB-2 protein -> activates RAS and MAP kinase

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18
Q

What is the ultimate function of the RAS dependent insulin signaling pathway?

A

increases transcription of glucokinase -> phosphorylates glucose in first step of glycolysis

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19
Q

Insulin signaling: what binds to phosphorylated IRS-1 in the RAS independent pathway? What does this cause?

A

binds to phosphoinositide-3-kinase (PI3 kinase) -> acts as second messenger for protein kinase B (PKB)

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20
Q

What is the ultimate function of the RAS independent insulin signaling pathway?

A

PKB plays a role in movement of GLUT4 into cell membrane and activation of glycogen synthase

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21
Q

Explain the process by which glucose triggers release of insulin into the blood stream

A
  • glucose enters pancreatic B cells through GLUT2 (facilitated diffusion)
  • enters glycolysis -> ATP produced
  • ATP acts on K channel in cell membrane -> depolarization
  • depolarization causes opening of Ca channels -> release of insulin granules
22
Q

What is the MOA of sulfonylurea drugs?

A

treats NIDDM -> targets K channels in pancreatic B cells and causes depolarization w/o presence of glucose

23
Q

What are the 3 domains of nuclear receptors?

A
  • ligand binding domain (LBD)
  • activation function 1 domain (AF1) - aka transcription activating domain
  • DNA binding domain (DBD)
24
Q

Which domain on NRs remains the same throughout all NRs?

A

DNA binding domain -> binds to HRE

25
What are 2 types of estrogen receptors (ERs)?
- ERa: mostly in female reproductive tract | - ERb: mostly in ovaries and prostate
26
What is the MOA of ERs?
promotes histone acetyl transferase (HAT) to loosen chromatin structure and enhance transcription
27
What is the MOA of Tamoxifen? What is it used to treat?
- antagonist of ERs - recruits proteins like histone deacetylase (HDAC) which is the opposite of HAT -> stabilizes nucleosome structure and prevents transcription - used to treat breast cancer
28
What controls the short term and long term stress response by the adrenal glands?
- short term: nerve impulses -> release of catecholamines | - long term: steroid hormone signaling -> release of mineralocorticoids and glucocorticoids
29
What enzyme catalyzes conversion of cholesterol to pregnenolone?
desmolase - rate limiting step of steroid hormone synthesis
30
What is the precursor to corticosteroids and androgens?
progesterone
31
What positively regulates desmolase?
ACTH
32
How is cancer related to ACTH?
tumor cells can activate ACTH receptor w/o the presence of ACTh and turn on massive cortisol production and cell proliferation
33
What helps convert prenenolone to progesterone?
hydroxysteroid dehydrogenase (HSD)
34
What is the general function of glucocorticoids?
mediates stress response by increasing protein catabolism, gluconeogenesis, and reducing inflammation; increases BP and Na uptake by kidneys
35
What is an example of a glucocorticoid and what receptor does it bind to?
Cortisol: binds to glucocorticoid receptor (GR)
36
Explain the importance of glucocorticoids in infants
- there is a burst of glucocorticoids during delivery that stimulates production of surfactant (allows lung expansion) - premature infants may not have burst -> leads to infant respiratory distress syndrome
37
What is the general function of mineralocorticoids?
increase Na/H2O retention, K excretion, and BP
38
What is an example of a mineralocorticoid and what receptor does it bind to?
Aldosterone: binds to mineralcorticoid receptor (MR)
39
What is an example of an androgen and what receptor does it bind to?
testosterone: binds to androgen receptor (AR)
40
How do women generally present w/ congenital adrenal hyperplasia (CAH)?
- hirsutism: excessive body hair in men and women on body parts usually absent of hair - also present w/ general oligomenorrhea and infertility
41
Which enzyme is defective in 95% of cases of CAH?
21-hydroxylase (pathways to aldosterone and cortisol
42
Which enzyme is defective in 5% of cases of CAH?
11B-hydroxylase (pathways to aldosterone and cortisol)
43
What happens to ACTH and androgen levels when production of glucocorticoids and mineralocorticoid can't occur?
- Excessive androgen production (only route it can take) | - increased ACTH (can't stimulate cortisone/aldosterone production)
44
CAH: Why does 17-a-hydroxyprogesterone accumulate?
fork in the road between androgens and cortisol (can't make cortisol)
45
CAH: How does accumulation of 11-deoxycorticosterone lead to HTN?
it is an MR agonist -> leads to disregulated salt and water balance (promotes Na and water retention and lower plasma K)
46
CAH: how does 21-a-hydroxylase deficiency lead to salt wasting?
- lack of aldosterone being produced -> high rate of Na loss in urine
47
What are 2 steroid hormone blood transport proteins and where are the made?
corticosteroid-binding globulin (CBG) and sex steroid binding globulin (SHBG) - both made in the liver
48
What is 17,20-lyase? What does deficiency (ILD) lead to?
- gateway enzyme from progesterone to all sex steroids | - impaired production of androgen and estrogen sex steroids
49
How will ILD present in males and in both sexes?
- Males: psuedohermaphroditism | - Both sexes: reduced/absent puberty, child like appearance in adulthood
50
Does ILD result in adrenal hyperplasia or HTN?
No - doesn't affect glucocorticoids or mineralcorticoids
51
What is the function of aromatase in females?
FSH stimulates aromatase to produce estrone; also converts testosterone -> estradiol (requires FSH and aromatase)