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04-BS-12 · May 2018

Question 2 of 13: Cholic Acid → Bile Salt — Amphiphilic Lipid Transport

Nivaar worked solution (AI-drafted; not reviewed by a licensed engineer)

Notes on this paper

National Exam 04-BS-12, Organic Chemistry — May 2018. 3 hours, closed-book examination (one Casio/Sharp-approved calculator and one hand-written aid sheet permitted); NOTES on page 1 state that TEN (10) questions constitute a complete exam paper and only the first 10 as they appear in the answer book are marked, but this sitting prints 13 numbered questions — every question and sub-part below is answered in full.

Reference texts: McMurry, Organic Chemistry, 9th ed. (drug acid–base/salt pharmacokinetics, steroid/bile-acid amphiphilicity, arene-oxide metabolism, cyclopropane stereochemistry and CIP assignment, reaction-energy diagrams, ester equilibria and intramolecular effective molarity, SN2 stereochemistry at a common stereocentre, named-drug synthesis design, epoxide ring-opening stereochemistry, mass-spectral formula discrimination, opioid IR/NMR structure elucidation, keto–enol tautomerism and conjugation/acidity, and condensation-polymer monomer identification). Every molecular formula, mass-balance, exact-mass, and stereochemical (R/S) assignment below.

Question 2: Cholic Acid → Bile Salt — Amphiphilic Lipid Transport (equal value)

Question text not reproduced: the examination questions are © Engineers and Geoscientists BC. Open the official past paper (linked at the top of this page) to read the question, then follow the worked solution below.


Cholic acid (top) is conjugated with taurine (H2N–CH2CH2–SO3H) to give sodium taurocholate (bottom), a bile salt.

Cholic acid's steroid nucleus is a rigid, curved, almost entirely hydrocarbon framework carrying three –OH groups on its concave face and two angular methyl groups on its convex face. This gives the whole ring system a facial amphiphilicity: one broad face is hydrophilic (the hydroxyl-studded concave side), the opposite face is hydrophobic (the methyl-studded convex side) — unlike a classic soap, which is amphiphilic end-to-end (polar head, non-polar tail) rather than face-to-face.

Conjugating the C-24 carboxylic acid with taurine (forming an amide) does two things: (1) it caps the molecule with a strongly polar, permanently ionised sulfonate group (pKa « 7, so it is anionic at physiological pH, unlike the parent carboxylic acid which is only partly ionised), sharpening the polar/non-polar contrast; and (2) it supplies the soap-like "head group" that a classic surfactant needs. In water, bile salt molecules orient their hydrophobic (convex) faces toward each other and toward dissolved lipid droplets, while their hydrophilic (concave/sulfonate) faces stay in contact with the surrounding water — exactly the same amphiphile-at-an-interface logic that lets ordinary soap emulsify grease. The result is a micelle (here often a small, disc-like or "bile salt/lipid mixed micelle") that encapsulates otherwise water-insoluble dietary lipids (triglycerides, cholesterol, fat-soluble vitamins) and keeps them dispersed in the aqueous intestinal contents long enough for lipase enzymes to act on them and for the products to be absorbed.