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13 Cards in this Set
- Front
- Back
Liver functions (10)
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1. blood glucose
2. make and eliminate cholesterol 3. make and export VLDL (TG) 4. make bile 5. make and export ketone bodies 6. urea cycle eliminate ammonia 7. make and elimante blood proteins 8. make heme and eliminate bilirubin 9. make and salvage pruine/pruimidine 10. make special moleucels - creatine, sulfate, traurine, niacine |
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Liver detox
process endogenous/xenobiotic (3) phase I (4) and II (5) reactions |
(A) process endogenous: to active form
(B) process xenobiotics 1. active 2. inactivate/eliminate 3. turn into toxins/carcinogens (C) Phase I: 1. reduction 2. oxidatin 3. hydroxylation 4. hydrolysis (D) phase II 1. conjugation 2. sulfation 3. acetylation 4. methylation 5. glucuronidation |
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cytochrome P450
what is it, type of rx, location roles (5) |
1. heme proteins
2. catalyze oxidation of molecules 3. in prokaryotes, all mammalina except RBC and SK MM Roles 1. steoid hormone production 2. metabolism of FA, PG, LT, retinoids 3. active/inativate therpauetic 4. convert chemical to reactive molecules -> cell death 5. induction/inhibiton of drug-drug interactions |
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general CP450 action
steps in priming cyt p450 for action |
(A) NADPH + H + O2 + A-H -> NADP + H2O + A-OH
(B) NADPH pass e- to FAD/FMN DH and reduce iron ion of cyt p450 then oxygen bind to modify substrate (C) monooxygenation, one atom of O2 goes into substrate A. |
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P450 locations in cell and components
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1. SER
(a) flavoprotein-NADPH-cyt-450-reductage (FAD, FMN) (b) e- from NADPH, FAD, FMn, cytp450 2. Inner mito membrane) (a)NADPH-adrenodoxin reductase (FAD) (b) NADPH -> FAD -> adrenodoxin (2 iron clusters) -> cytop450 |
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CytoP450 activate endogenous biomolecules I
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1. Synthesis of cortisol, aldosterone
(a) CE -> pregnenlone - CYP11A1, 3 NADPH + O2 steps - commitment step - adrneal mito (b) pregnenolone -> progesterone - oxidation - cytosol (c) progesteron -> DOC - ER - Cpt P21 (d) DOC -> ALDOSTERONE - hydroxylation CYP11B2 - mitochondrial (e) pregnenoloen/progesterone -> CORTISOL - CYP17 ER - CYP11B1 Mit - zona fasciculata 2. synthesis of sex hormones (a) 17 a-hydroxypregnenolone/hydroxyprogesterone -> DHEA/androstenedione - CYP17 - lose acetyl group (b) DHEA -> testosterone (androgen) - sex organs (c) androgen -> estrogen - CYP19 (many hydrozylation) - aromatase (aromatization) |
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deficiency in CYP 21A2
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(a) congential adrenal hyperplasia (CAHs)
(b) insufficient cortisol production (c) deficieny CYP21A2 to convet 17-a-OH-progesterone to 11-deoxycortisol to cortisol (d) increase pituitary ACTh -> adrenal hyperplasia, DHEA, androstenedione (e) virilization in females |
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CytoP450 activate endogenous biomolecules II
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Oxygenation of PG and vitamin D activation
(1) D3-> 1,25-dihydroxy D3 - CYP27 - activate (2) LTB4 -> 20 hydroxyLTB4 - CYP4 - less chemotactic |
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CytoP450 oxidize xenobiotics
general (6) |
(a) Make lipophilic substance more soluble.
(b) in liver (some in intestine) (c) phase I: oxidation, functioan group added to cytochrome p450 (d) phase II: biosynthetic reactions, small polar endo molecule added to funcation group. (e) smooth ER, competitionof many substrate adb inducible by best substrate (f) 3A4: 50% drugs, 2D6: 20%, 2C9,19: 15% , 1A2&2A6&2B6: 15% |
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CytoP450 oxidize xenobiotics activate, inactive/eliminate
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Terfenadine -> fexofenadine
(a) activated (hydroxylated) by CYP3A4 (b) eyrthromycin/ketoconaole: inhibit of CYP3A4 -> toxic build-up. acetaminophne - sulfation & glucuronidation - inactivate and eliminate (1) acetomenophen -> NAPQ1 - CYP2E1 (2) NAPQ1 -> nontoxic - conjugation wtih glutathione (3) CYP2E1 induced by alcohol Statins (1) CYP3A4 liminate (2) grapefruit juice inhibit CYP3A4 -> statin build up. |
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CytoP450 oxidize xenobiotics
form toxins |
benzopyrene-> benzopyrene dihydrodiolepozide
- carcinogen by CYP1A |
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cytochrome p450 inhibitor and regulators
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inhibitor: CO
CYP2E1: ethanol induces CYP3A4: induce by 21 carbon steroid, carbamazepine, rifampin, SJW CYP2B2: induced by phenobarbital CYP3A1: phenobarbital |
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Polymorphism, poor metabolizers
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decifiency
CYP2D6: debrisoquine, sparteine, amytruptyline, dextromethorphan, codeine CYP2C19: methytoxin, CYP2C9 warfarin |