RQ5 - Name: Key Due: Review Questions — Distribution and...

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Unformatted text preview: Name: Key Due: Review Questions — Distribution and Elimination ‘1. From relation (a) below torthe protonated and unprotonated forms of a given weak acid or base (acid 2 base + H+), derive the Henderson-Hasselbaich relation (b). (a) K61 = [5+[lbase1 we log Ka = iog [H+] + log |basei [acid] [acid] -log [H+} + log Ka = log lbasei [acid] But pH = -log [H+] and {Ma 2 ~tog Ka Thus the above expression is equivalent to (b) (b) pi—l - pKa = log lbasel [acid] 2. Upon absorption into the bloodstream. aspirin (acetylsalicylic acid) is hydrolyzed to saiicylic acid (pKa = 3), shown below. Suppose a person taking an overdose of aspirin is given a iarge dose of sodium bicarbonate, raising the pH of the urine in the distai tubuie of the nephron from 5.5 to 7.5. Will this enhance elimination of salicyiic acid in the kidney? Explain. Q coon w G COOH ——> Carboxyl group ionization OH OCOCHa salicylic acid Ware 3 A B Since A is freely ditiusible, assume it is equaliy concentrated in plasma and urine at equiiibrium. When the urine is pH 5.5, [B] is 100 times higher in plasma than in urine and is therefore eliminated slowly. However, when the urine is pH 7.5, [B] is the same in plasma and urine and thus is eliminated much faster. Piasma pH = 7.5 i Urine pH = 5.5 Urine pH m 7.5 1 log ital = 4.5 i log E = 2.5 log _LBj_ = 4.5 [A] | [A] [A] l —-> 1131 a 30,000 i —> _[i_3l as 300 6 fl 2 30,000 [A] 1 I [A] t [A] 1 3. Dibutylnitrosamine (a) is partially converted in the liver to butylcarboxypropyl- nitrosamine (b), which concentrates in the urine. The latter compound causes bladder tumors in the rat, presumably upon activation by a-hydroxylation. Trace the metabolic pathway leading from (a) to (b) using enzymatic reactions discussed in class. include enzymes and cotactors. N=O | (a) CHg-CH3~CH2-CH2—N-CH2~CH2—CHg-CH3 (Let this compound be ROI-13) J, (urhydroxyiation by cytochrome P450) RCHEOH t (alcohol dehydrogenase, NAD+) RCHO l (aldehyde dehydrogenase, NAD+) N==O l (b) CHg-C Hg—C HZWCHZ- N~CH2—C Hz-C Hz-COOH 4. Trace a plausible pathway by which 4naminobiphenyl gives rise to macromolecular adducts in the bladder. R—NHZ Let R : biphenyl i R—NHOH Hydroxylation in hepatocytes l R—NHO-glucuronic acid Conjugation in hepatocytes l R-NHOH Deconjugated by acidic conditions in urine. 3 also by giucuronidase in urine R-NHOSOg“ Conjugation in bladder cells. J, sultation (shown) or acetylation [R—NH+] Unstable conjugate decomposes l R-NH~DNA DNA adduct forms ...
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This note was uploaded on 03/27/2011 for the course ETX 103A taught by Professor Etx during the Winter '06 term at UC Davis.

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RQ5 - Name: Key Due: Review Questions — Distribution and...

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