Biochemistry Exam 3 - UCIMED
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- Essay: Conditional Knockout
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in nervous system ^G in blood
neg feedback of HPA axis req. G
-less anxious-->role of G in learning, anxiety, memory in neurons - Essay: Knock-in
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-mutation causing failure of receptor dimerization and DNA binding.
-mice survived
-suggests G ^imp't Prot/Prot int.
-reg. of xscrip factors - Essay: Mutation in Human: disease and treatment
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-Adrenal Hyperplasia & ^ ACTH (-->^GR)
-from a pituitary tumor (Cushing's)
-Adrenal Neoplasia
-^ use of glucocorticoid - Essay: What happens in nucleus
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GR bound by cortisol (g-coritcoid):
1. binds GRE: represses or activates xscription
2. protein:protein interaction - regulates xscrip. factors (AP1&NF-kB) - Essay: Mechanism of action
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stress (physical: infection/injury or emotional)
-->hippocampus, amygdala-->hypothalamus -(CRF&AVP)-> Pituitary -(ACTH)-> Adrenal Glands --> secrete glucocorticoid (inhib. ACTH&CRF) --> cyto. G receptor --> nucleus - Essay: Syndrome, causes, symptoms
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Cushing Syndrome
causes ^glucocorticoid (hypercortisolism)
symptoms: obesity, hypertension, osteoporosis, diabetes - Physiological Jaundice
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^ unconjugated bilirubin in newborns due to low UDP-glucuronyltransferase (b/c liver not fully developed)
--mild form doesnÂ’t reqÂ’ treatment & improves
--severe form needs treatment: fluorescent light
However, if thereÂ’s ^ levels of conjugated bilirubin, means impaired removal (ie liver damage, bile duct obstruction) -
Jaundice
Reason #2 for Decreased Excretion - 1.bile duct obstruction(obstructive or posthepatic jaundice) 2. decreased bilirubin excretion (note:rate of bilirubin excretion correlates w/ rate of bile flow) 3.^conjugated bilirubin
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Jaundice
Decreased Excretion b/c of: - 1. liver damage(hepatocellular or intrahepatic jaundice) 2.decreased bilirubin uptake and conjugation 3.^levels of unconjugated bilirubin (dangerous! Unconjugated bilirubin in excess of albumincapacity„³binds lipids; impairs membrane funct. esp. in nervous system)
- bilirubin turnover
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By labeling glycine*
early-early
Heme turnover in liver (15%)
early-late \
in liver and bone marrow
(poorly incorporated or
easily released from RBC)
^ w/ diseases ie. pernicious anemia
, thalassemia
late
in RBCÂ’s (85%) - HEME DEGRADATION
- RBCÂ’s>Heme>biliverdein>bilirubin>complexedw/albumin>conjugated w/glucuronic acid>bile>unconjugated bilir.>urobilinogen>urobilin(stercobilin in feces) or urobilin in kidney.
- HEME: what makes it up and location of steps
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-4 pyrrole rings, 4methylene bridges, synthesized mostly in Liver & bone
-marrow, of the 8 steps, the 1st & last 3 steps are in the mitochondria, 2nd –
5th steps are in cytosol, only Uroporphyrin III is acceptable to body (itÂ’s
assymetrical w/AÂ’s(acetate) & PÂ’s (propionate). - HEME : Found in
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: 1.hemoglogin (binds O2) 2.myoglobin 3. cytochromes (e- carrier
(p450) 4. catalase(part of active site) - Phy Active Amines: characteristics
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1.All are neurotransmitters 2. All are excitatory except GABA,Gly, Taurine(inhibitory).
a.a.--------------------„³amines
1.Decarboxylation w/PLP cofactor (and/or)
2. Hydroxylation w/ BH4 - NITRIC OXIDE
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NO
R--------------„³Citrulline
NO synthase
NADPH NADP+ - NO char
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1.diffuses freely through membranes 2.short ½
life 3.reactive 4. cell signal molec. 5. smooth muscle relaxer 6.prevents platelet aggre. 7.nuerotransmitter 8.made in macrophages as a bacterial/cancer killer - SERATONIN: MNEM
- “Small Wimpy Trashy Person is Depressed” so he “Pax” his “Prosac”
- GABA (γ-aminobutyric acid): MNEM
- someone who “GAB”s a lot can be “inhibited” by “GluEing” their mouth shut.
- Glutamate(E) characteristics
- is excitatory and found in all neurons GABA is inhibitory and found in only inhibitory neurons. They’re opposites! Some epileptics have decreased GABA levels—treated w/ Valproic Acid = ^GABA
- Heme synthesis: overall rxn
- 8 glycine + 8 succinyl CoA + Fe 2+ ---„³ ---„³ Heme
- ALA locations
- ALA 1 in liver & ubiquitous, ALA 2 in bone marrow
- PORPHYRIAS: Enzymatic abnormalities:
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Hepatic & neuropsychiatric effects
Causes ^ALA & PBG and/or with decreased heme in cell body fluids. - CREATINE: MNEM
- you want to “Create” (Creatine) or “GROw” muscle ever since you “Met” “SAM” the trainer
- GSH: MNEM
- lowers ROSÂ’s, analogs increase tumor sensitivity to ROS from irradiation
- Bilirubin in blood =
- unconjugated / indirect bilirubin (w/ colorimetric RXN in methanol.
- Bilirubin in bile =
- conjugated/ direct bilirubin (w/ colorimetric RXN in aqueous solution)
- Heme Sources:
- 85% RBCÂ’s, 15% immature RBC turnover; liver and other extraerythroid tissue.
- JAUNDICE
- Yellowing of skin and white of eye from bilirubin depositionÂ… caused by 1.^production or 2. decreased excretion
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jaundice:
Increased Production b/c of: - 1.excess hemolysis(hemolytic/prehepatic jaundice) 2. insufficient conjugation or complexing 3. ^levels of unconjugated bilirubin (dangerous!)
- Essay: Knockout
- die shortly after birth due to low production of surfactants--> respiratory failure