BC Test 2 Flashcards
(61 cards)
1
Q
Testosterone ->estradiol
A
Aroma taste
2
Q
DHT development
A
External genitalia
3
Q
Estradiol development
A
Bone, libido
4
Q
Testosterone development
A
Wolffish, internal gonads, skeletal muscle
5
Q
Deficiency of androgen commonly due to (2)
A
- Deficiency of Cyp17 hydroxylase
- would result in entirely female external genitalia, lack of internal & external organ development - Deficiency of 5alpha reductase
- failure of external genitalia but internal development unaffected, can’t complete puberty
6
Q
ER-alpha
- Affects
- Inhibit or activate?
A
- Endometrium, ovary, mammary gland, hypothalamus, endothelial cells, vascular smooth muscle
- Activate
7
Q
ER-beta
- Affect
- Inhibit or activate?
A
- Kinsey, intestinal mucosa, lung, bone, brain, prosit state, vasculature
- inhibit
8
Q
Estradiol and receptor binding
A
Equally binds alpha or beta, nonspecific
9
Q
Estrone and ER binding
A
Alpha favored, present continually
10
Q
Estriol and ER binding
A
Beta favored, but both very low affinity
-present during pregnancy
11
Q
Estradiol binding to ligand binding domain steps
A
- A large hydrophobic pocket is formed by alpha helix scaffold
- Estradiol is sealed within LBD by helix 12
- Allows activators to bind in AF2 site
When antagonist present:
Helix 12 is stuck in the spot where coactivators need to bind, therefore no activation
12
Q
Estrogen synthesis in premenopause
A
Gonadotropins increase cholesterol side-chain cleavage and Aromatase
Ovaries produce estrogen and progesterone
13
Q
Estrogen synthesis in Postmenopause
A
Synthesized in adipose
Adrenal gland secretes DHEA, an androgen precursor
14
Q
Estrogen synthesis in males
A
Produced by testes
Circulating estrogens formed from androstenedione and DHEA
15
Q
5 key points of signal transducing systems
A
- Specificity
- Amplification
- Modularity
- Desensitization/adaptation
- Integration
16
Q
Alpha 1 receptors
A
Bind agonists, affect smooth muscle contraction and vasoconstriction of skin
17
Q
Alpha 2 receptors
A
Bind agonists, inhibit release of NE and contraction of anal sphincter
18
Q
Beta 1 receptors
A
activation results in increased HR and force of contraction
19
Q
Beta 2 receptors
A
Activation results in vasodilation and bronchodilation, smooth muscle relaxation
20
Q
Isoproterenol
A
Mimic Epi, agonist
Treatment for bradycardia or branch block
21
Q
Propranolol
A
Non-selective B blocker
Antagonist
22
Q
GPCR Pathway
A
- Epi binds receptor
- GDP bound GSa replaced by GTp, activating GSa
- GSa separates from Gby, moves to adenylyl cyclase and activates it
- Adenylyl cyclas catalyzes ATP ->cAMP
- cAMP activates PKA
- PKA phosphorylates inducing cellular response
- cAMP degraded by phosphodiesterase (cAMP -> 5AMP)
23
Q
Gsa has
A
intrinsic ATPase activity, meaning it can hydrolyze the GTP to GDP, making inactive
24
Q
Termination of B-adrenergic receptor response
A
- [Epi] drops, hormone dissociates from receptor, Gsa inactive
- Gsa hydrolyzes GTP, reconnects with Gby
- Phosphodiesterase hydrolyzes cAMP
- Phosphorprotein phosphatase degrades PKA
25
Desensitization of B-adrenergic receptor
Termination even when conc is high
1. Gby recruits BARK
2. BARK phosphorylates receptor, no Barr can bind
3. Barr causes endocytosis of receptor
26
in low-energy state, PKA activates
CREB
27
PGE1
Binds to adipose cells to slow mobilization of FA and counteract Epi
28
IP3 pathway
1. Hormone binds GPCR
2. GTP binds Gq
3. GTP-Gq binds and activates PLC
4. PLC cleaves PIP2 to IP3+DAG
5. IP3 diffuses to ER and binds IP3-gated Ca++ channels, Ca rushes in to cytosol
6. DAG interacts with Ca to activate PKC
29
Insulin receptor tyrosine kinase
1. Insulin binds 2 extra cellular alpha subunits (homodimer)
2. Homodimer interacts with 2 beta subunits -> active insulin protein receptor
3. Autophosphorylation of receptor
4. INSR phosphorylates IRS-1
5. IRS-1 goes to Grab 2
6. Grab 2 binds SOS
7. SOS binds Ras, causing exchange of GDP for GTP
8. RAS-GTP activates RAF1
9. RAF1 phosphorylates MEK
10. MEK phosphorylates ERK
11. ERK moves into nucleus
30
IRS-1 interaction with PI3K
1. IRS-1 activates PI3K
2. PI3k converts PIP2 to PIP3
3. PIP3 phosphorylates PKB
4. PKB phosphorylates glycogen synthase 3 kinase GS3K causing INACTIVATION, therefore activating GS
5. PKB also stimulates Glut4 movement to membrane to increase glucose uptake
31
JAK-STAT pathway
1. Epo binds Epo receptor
2. JAK is recruited and phosphorylates receptor
3. STAT5 attracted to receptor and comes in close proximity to JAK, and becomes phosphorylated
4. 2 phosphorylated STAT5s form a dimer
5. Dimer can enter nucleus as transcription factor to regulate expression of genes for RBC synthesis
32
conversion of GTP->cGMP
Guanylyl cyclase
33
cGMP activates
PKG
34
Membrane bound guanylyl cyclase
Homodimer
| Responds to atrial naturetic factor
35
Soluble guanylyl cyclase
Heme containing enzyme
Response to intracellular NO concentration
Present in smooth muscle of heart and blood vessels and leads to smooth muscle contraction
36
Pathway when atrial naturetic factor released
1. When blood volume too high, atrium released ANF
2. ANF binds to ANF receptors in collecting ducts of kidneys and vascular smooth muscle
3. [cGMP] increases in collecting ducts
4. Triggers release of Na and renal excretion of H20 -> blood volume decreases
37
Nitric oxide production
Arginine -> citrulline by nitric oxide synthase
| -needs Ca++, NADPH and O2
38
Viagara
Inhibits phosphodiesterase, therefor keeps cGMP high
39
Acetylcholine presence?
- All preganglionic autonomic
- Most postganglionic parasympathetic
- Some postganglionic sympathetic
40
ACh synthesis, storage, breakdown
1. Choline taken up in diet
2. transported to nerve terminal via choline transporter
3. Choline + acetyl Coa acted on by choline acetyltransferase
4. ACh stored in vesicles by VATs
5. VAT fuses SNAP with SNARE and releases ACh to cleft
6. Acetylcholinesterase degrades in synaptic cleft
41
Butylcholinesterase
Degrades ACh and opiates
| Not as fast as acetylcholinesterase (pseudocholinesterase)
42
Botulinum toxin
Blocks ACh release by preventing SNARE from binding
43
Catecholamine synthesis pathway
1. Phe to L-tyrosine by Phe hydroxylase, tetrahydrobiopterin
2. L-tyrosine to L-DOPA by L-tyrosine tyrosine hydroxylase, tetrahydrobiopterin
3. L-DOPA to Dopamine by DOPA decarboxylase
4. Dopamine to NE by dopamine B-hydroxylase
5. NE to Epi by PNMT, SAM in chromaffin granules of adrenal gland
44
Glucocorticoid affect on Catecholamine synthesis
Upregulate PNMT, therefor favor Epi production
| Also induce TH and DBH
45
Catecholamine transporters (3)
1. NET - takes NE from cleft to nerve terminal
2. VMAT2 - takes from cytoplasm to storage vesicle
3. ENT - uptake into extra neuronal cells
46
Dopamine degradation
1. Dopamine to DOPAL by MAO
2. DOPAL to DOPAC by aldehyde DH
3. Into blood
4. DOPAC to HVA by COMT
47
NE degradation
1. NE to DOPEGAL by MAO
2. DOPEGAL to DHPG by aldehyde reductase
3. Into blood
4. DHPG to VMA by COMT
48
Epi degradation
1. (In blood) Epi to metanephrine by COMT
2. Metanephrine to MHPG by MAO
3. MHPG to VMA by aldehyde DH
49
Monocarboxylic acids
Commonly cause inhibition
| Include GABA, glycine, taurine and B-alanine
50
Dicarboxylic acids
Commonly cause activation
| Glutamine and Aspartate
51
GABA shunt pathway
1. aKG transaminase from Krebs to L-glutamate by aKG, PLP
2. L-Glu to GABA by GAD
3. GAD to succinic semialdehyde by aKG transaminase, PLP
4. Succinic semialdehyde to succinic acid by succinic semialdehyde DH
52
Serotonin synthesis and degradation
1. Typ to 5-hydroxytrptophan by tryptophan hydroxylase, tetrahydropterine
2. 5-hydroxytrptophan to 5-hydroxytrptamine by AADC, vitB6
3. 5-HT to 50HIAA by MAO
53
Ionotropic receptors have ______ effect and metabotropic have ______ effect
Ionic - immediate
| Metabotropic - long-acting
54
Nucleobases attach pentose at ________ with ______ bond
Purines attach at
Pyrimidines attach at
Anomeric C
B-N-glycosidic
Purines attach at N9
Pyrimidines attach at N1
55
Purines include
Adenine (amino group in top left)
| Guanine (carbonyl top left, amino bottom left)
56
Pyrimidines include
Cytosine (carbonyl bottom left, amino at top)
Uracil (2 carbonyls)
Thymine (2 carbonyls and a methyl)
57
Mycophenolate mofetil
Inhibits inosine monophosphate dehydrogenase, therefor stopping B-cells from making inosine
58
DNA - 1 turn is how many residues and Angstroms
10 residues
| 36 Angstroms
59
Hogsteen base pairing
H bonds b/t 3 or 4 nucleotides
| Common near prontooncogenes
60
IMP construction (half - only what we need to know for this test)
1. PRPP to 5-phospho-B-D-robosylamine by glutamine-PRPP amino transferase and Gln
2. 5-PBDRA to GAR by GAR synthetase and gly, ATP
3. GAR to FGAM, FGAM to AIR by AIR synthetase and ATP (cyclyzes)
4. AIR to CAIR by AIR carboxylate (direct methylation w/out biotin)
61
Testosterone -> DHT
5alpha reductase
