| Cholesterol cannot be metabolized by mammalian cells
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| STEROID 21-HYDROXYLASE DEFICIENCY |
A neonate was born with ambiguous genitalia. Within 48 hours the infant was hypotensive and distressed. Biochemical investigation reveals:
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Comment. This baby had a severe form of steroid 21-hydroxylase deficiency, the commonest of a range of conditions that are characterized by defects in the activity of one of the enzymes in the steroidogenic pathway and known as congenital adrenal hyperplasia. The conditions have a genetic basis leading to a failure to produce cortisol (and also possibly aldosterone). As a result there is reduced negative feedback on the pituitary production of ACTH, which then continues to stimulate the adrenal gland to produce steroids upstream of the enzyme block. These include 17-hydroxyprogesterone, which is further metabolized to testosterone (see Fig. 16.7) resulting in androgenization of a female neonate. The renal salt wasting is the result of mineralocorticoid deficiency and requires urgent treatment with fluids and steroids. Long-term maintenance therapy with hydrocortisone and a mineralocorticoid suppresses ACTH and androgen production. |
| A less severe form of this condition or partial enzyme deficiency occurs in young women who present with menstrual irregularity and hirsutism, as a consequence of excess of adrenal androgens. |
| Cholesterol cannot be digested in the gut or broken down by mammalian cells into carbon dioxide and water. Removal from the body is thus dependent on transfer into the gut prior to excretion via the feces. As we discussed in the section on bile acids above, there is a considerable flux of cholesterol, either directly or in the form of bile acids, from the liver into bile and then into the duodenum via the common bile duct. About 1g of cholesterol is eliminated from the body each day
through the feces. Approximately 50% is excreted after conversion to bile acids. The remainder is excreted as the isomeric saturated neutral sterols coprostanol (5β-) and cholestanol (5α-) produced by bacterial reduction of the cholesterol molecule.
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