Hydroxylation of steroids by microorganisms

Apparent combined P450C17 and P450C21 deficiency (see 613571) is a rare variant of congenital adrenal hyperplasia, first reported by Peterson et al. (1985). Affected girls are born with ambiguous genitalia, indicating intrauterine androgen excess. After birth, however, virilization does not progress and amounts of circulating androgens are low or normal. Affected boys are sometimes born undermasculinized. Boys and girls can also present with bone malformations. Findings of biochemical investigations of urinary steroid excretion in affected patients have shown accumulation of steroid metabolites, indicating impaired C17 and C21 hydroxylation, suggesting concurrent partial deficiencies of the 2 steroidogenic enzymes, P450C17 and P450C21. However, sequencing of the genes encoding these enzymes showed no mutations, which accorded with the idea of a defect in a cofactor that interacts with both enzymes.

These three reactions are catalyzed by very large, multi-subunit enzymes prolyl 4-hydroxylase , prolyl 3-hydroxylase and lysyl 5-hydroxylase , respectively. These reactions require iron (as well as molecular oxygen and α-ketoglutarate ) to carry out the oxidation, and use ascorbic acid (vitamin C) to return the iron to its reduced state. Deprivation of ascorbate leads to deficiencies in proline hydroxylation, which leads to less stable collagen, which can manifest itself as the disease scurvy . Since citrus fruits are rich in vitamin C, British sailors were given limes to combat scurvy on long ocean voyages; hence, they were called "limeys". [ citation needed ]

Hydroxylation of steroids by microorganisms

hydroxylation of steroids by microorganisms

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