Fbn

"OH Glycocholic acid

FIGURE 25.41 • Cholic acid, a bile salt, is synthesized from cholesterol via 7a-hydroxy-cholesterol. Conjugation with taurine or glycine produces taurocholic acid and glycocholic acid, respectively. Taurocholate and glycocholate are freely water-soluble and are highly effective detergents.

COO-

"OH Glycocholic acid

FIGURE 25.41 • Cholic acid, a bile salt, is synthesized from cholesterol via 7a-hydroxy-cholesterol. Conjugation with taurine or glycine produces taurocholic acid and glycocholic acid, respectively. Taurocholate and glycocholate are freely water-soluble and are highly effective detergents.

NADP+

Cytochrome P450 reductase (Flavin)

Cytochrome P450 reductase (Flavin)

7a-Hydroxylase (Cytochrome P450)

Fe2+

NADP+

Cytochrome P450 reductase (Flavin-H,)

Cholesterol 7a-Hydroxycholesterol

7a-Hydroxylase (Cytochrome P450) Fe

FIGURE 25.42 • The mixed-function oxidase activity of 7a-hydroxylase.

Cholesterol 7a-Hydroxycholesterol

Because they contain both nonpolar and polar domains, these bile salt conjugates are highly effective as detergents. These substances are made in the liver, stored in the gallbladder, and secreted as needed into the intestines.

The formation of bile salts represents the major pathway for cholesterol degradation. The first step involves hydroxylation at C-7 (Figure 25.4i). 7 a-Hydroxylase, which catalyzes the reaction, is a mixed-function oxidase involving cytochrome P450. Mixed-function oxidases use O2 as substrate. One oxygen atom goes to hydroxylate the substrate, while the other is reduced to water (Figure 25.42). The function of cytochrome P450 is to activate O2 for the hydroxylation reaction. Such hydroxylations are quite common in the synthetic routes for cholesterol, bile acids, and steroid hormones and also in detoxification pathways for aromatic compounds. Several of these are considered in the next section. 7a-Hydroxycholesterol is the precursor for cholic acid.

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