Ll 3-Hydroxysteroids

The saxl (hypersensitive to abscisic acid and auxin) mutant probably has a defect in the oxidation and isomerization of 3p-hydroxy-A precursors to 3-oxo-A steroids (Ephritikhine et ah, 1999). AtHSDl (At5g50600) encodes a protein with homology to animal ll- 3-hydroxysteroid dehydrogenase (Li et ah, 2007) however, no obvious sequence similarities exist with the 3P-HSD involved in cardenolide bios)mthesis (see Section 6.3.1.2). 

Cortisone exhibits good systemic anti-inflammatory activity and low-to-moderate salt-retention activity after its due in vivo conversion to hydrocortisone acetate. Importantly, this conversion is duly mediated by ll 3-hydroxysteroid dehydrogenase. It exerts a host of therapeutic usages viz., collagen diseases, Addison s disease, allergic reactions, acute shock, and several other indications. 

A deficiency of ll -hydroxylase is the second most common form of CAH, with an incidence of 1 per 100,000 births, and is associated with manifestations of virilization, elevated concentrations of plasma androstenedione and DHEA-S, and hypertension. The mineralocorticoid-induced hypertension is caused by an elevation of DOC 11-deoxycortisol concentrations are markedly raised in subjects with this enzyme defect,The major distinguishing characteristic of this disorder from 21-hydroxylase deficiency, besides the elevated plasma concentrations of 11-deoxycortisol, is hypertension elicited by the salt retention caused by increased concentrations of DOC, A deficiency of 3 -hydroxysteroid dehydrogenase-isomerase has been reported and leads to an elevation in the ratio of 17a-hydroxypregnenolone to that of 17a-hydroxyprogesterone and to an increased ratio of DHEA to androstenedione. In severe forms of this rare disorder, female infants have pseudohermaphroditism, and male infants present with incomplete masculinization. Patients with this disorder usually present in early infancy with complete adrenal insufficiency including salt wasting. A late-onset form has also been reported in patients with premature pubarche with hirsutism, acne, and menstrual irregularities. The... 

Key to reactions (enzymes) 0, via mevalonate, isopentenyl phosphate, squalene 1, hydroxylase, desmolase (20,22) S, A -3j8-hydroxysteroid dehydrogenase, 5(4)-isomerase S, 21-hydroxylase 4, 17a-hydroxylase 6, ll 3-hydroxylase 6, desmolase (17,20) 7, 17 -hydroxysteroid dehydrogenase 8, 19-hydroxylase 9, aromatization. 

Figure 2 Biosynthesis of steroid hormones. Abbreviations of names of enzymes 20, 22-Des, 20,22-desmolase 17,20-Des, 17,20-desmolase 3 3-HSD, 3 3-hydroxysteroid-dehydrogenase 17 3-HSD, 17 3-hydroxysteroid-dehydrogenase 18-HSD, 18-hydroxyste-roid-dehydrogenase 17a-OH, 17a-hydroxylase 21-OH, 21-hydroxylase ll 3-OH, 11 3-hydroxylase 18-OH, 18-hydroxylase.

A microsomal retinol dehydrogenase catalyzes the oxidation of CRBP-bound all-trans-retinol to retinaldehyde it also acts as a Sa-hydroxysteroid dehydrogenase. A similar enzyme catalyzes the oxidation of 9-cis- and 11-cis-retinol, but not eill-trans-retinol again, it has Sa-hydroxysteroid dehydrogenase activity. In the eye, the major product of this enzyme is 11-cts-retinaldehyde, whereas in other tissues it is 9-c(s-retinaldehyde, which is then oxidized to 9-cts-retinoic acid (Section 2.3.2.1 Chen et al., 2000 Duester, 2000, 2001 Gamble et al., 2000 Napoli, 2001). Although there is known to be an isomerase in the eye for the formation of ll-c(s-retinaldehyde as a... 

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