Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Metabolism of Carbohydrates and Lipids
Synthesis, Transport, and Excretion of Cholesterol
Elimination of Cholesterol and Formation of Bile Salts - Biosynthesis of Bile Acids

Primary Bile acids are synthesized in the Liver from Cholesterol via a series of intermediates. Cholic acid is quantitatively the predominant bile acid. Cholic and chenodeoxycholic acids share a common precursor derived from cholesterol (Fig. 27.7).

The first step in The Biosynthesis of bile acids is the 7α-hydroxylation of cholesterol, which is the rate-limiting reaction in the biosynthetic pathway. It is catalyzed by the microsomal enzyme 7α-hydroxylase and requires oxygen, NADPH, and cytochrome P-450. Like the Enzymes involved in subsequent hydroxylation stages, 7α-hydroxylase is a typical monooxygenase. Vitamin C Deficiency inhibits bile acid formation at the 7α-hydroxylation step, leading to cholesterol accumulation; guinea pigs with scurvy develop atherosclerosis.

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Fig. 27.7. BIOSYNTHESIS AND DEGRADATION of bile acids. Asterisks indicate Reactions Catalyzed by microbial enzymes.

The biosynthetic pathway of bile acids branches at an early stage: one branch leads to The formation of cholic acid, which contains an additional α-OH group at position 12, whereas the other leads to chenodeoxycholic acid. Otherwise, both branches are similar and involve hydroxylation and side-chain shortening reactions (Fig. 27.7), resulting in structures characteristic of bile acids that feature α-OH groups at positions 3 and 7 and a fully saturated steroid Nucleus.

Normally, bile acids are secreted into the bile as conjugates with Glycine and taurine. Newly synthesized bile acids are believed to reside in hepatocytes as CoA esters, namely cholyl-CoA or chenodeoxycholyl-CoA (Fig. 27.7). These bile acid-CoA derivatives are formed by an activating enzyme localized in liver Cell microsomes. Another enzyme catalyzes the conjugation of these CoA derivatives with glycine or taurine to yield glycocholic or taurochenodeoxycholic acids, which are the primary bile acids. In humans, the normal ratio of glycine to taurine conjugates of bile acids is 3:1.

Since bile contains substantial amounts of sodium and potassium ions and is alkaline in reaction, it is customary to consider bile acids and their conjugates in the form of salts, hence the term "bile salts".

In the intestine, some of the primary bile acids undergo deconjugation and 7α-dehydroxylation by intestinal Bacteria, yielding secondary bile acids: deoxycholic acid from cholic acid, and lithocholic acid from chenodeoxycholic acid (Fig. 27.7).