Biosynthesis steroids

Fig. 9. Abbreviated steroid biosynthesis where DHEA = dehydroepiandrosterone and DHT = dihydrotestosterone.

NAD and NADP are required as redox coen2ymes by a large number of enzymes and ia particular dehydrogenases (Fig. 6). NAD" is utilized ia the catabohe oxidations of carbohydrates, proteins, and fats, whereas NADPH2 is the coenzyme for anaboHc reactions and is used ia fats and steroid biosynthesis. NADP+ is also used ia the cataboHsm of carbohydrates (2). 

The most important oxirane, from an anthropocentric viewpoint, is probably squalene oxide (72), a precursor of lanosterol (73) and thus of the maligned but essential cholesterol (74 Scheme 87) 78MI50501). The cyclization of (72) to (73) represents nucleophilic tr-attack on oxirane carbon cf. Section 5.05.3.4.3(t)()), and the process has also been extensively investigated in vitro (68ACR1). Oxiranes are even more ubiquitous in steroid biosynthesis than had been thought, for a cholesterol epoxide has been shown to be a product of mammalian steroid biosynthesis <81JA6974). 

The mechanism by which TBT causes these effects has been extensively stiidied. The androgenic effects of TBT appear to be caused by interference with steroid biosynthesis rather than by mimicking the action of testosterone at the androgen receptor. Exposure of female molluscs to TBT leads to an elevation in testosterone in the haemolymph. " Much of the experimental evidence... 

Figure 27.12 An overview of steroid biosynthesis from farnesyl diphosphate.

From lanosterol, the pathway for steroid biosynthesis continues on to yield cholesterol. Cholesterol then becomes a branch point, serving as the common precursor from which all other steroids are derived. 

Chapter 27, Biomolecules Lipids—The chapter has been extensively revised, with increased detail on prostaglandins (Section 27.4), terpenoid biosynthesis (Section 27.5), and steroid biosynthesis, (Section 27.7). 

This direct synthesis of steroidal pyrones should make a variety of structures related to the lucibufagins (as well as to the toad-derived bufadienolides) readily available for biological investigation for the first time. How the insects themselves manage to obtain their defensive pregnanes and steroidal pyrones remains a mystery, since insects are generally considered to lack the enzymatic machinery essential for steroid biosynthesis (19). In fact, we do not yet know whether these insect defensive steroids are produced de novo or whether they are derived... 

Haynes, R.C., and Murad, F. (1985). Adrenocorticotropic hormone adrenocortical steroids and their synthetic analogs inhibitors of adrenocortical steroid biosynthesis. In Goodman and Gilman s The Pharmacological Basis of Therapeutics (Goodman, A.G., Goodman, L.S., Rell, T.W. and Murad, F., Eds.). Macmillan, New York, pp. 1459-1489. 

Electrophilic additions to carbocations in terpenoid and steroid biosynthesis... 

High-dose progestins are used as last-line endocrine therapy [223]. They inhibit the adrenal steroid biosynthesis. The decrease of estrogen levels is comparable to that caused by the administration of aromatase inhibitors. In post-menopausal women, the progestin megestrol acetate (MGA) decreases serum plasma level of DEAH, androstenedione and cortisol to less than 10% [223,224]. 

NADPH), oxygen, and a specific cytochrome P450. The rate-limiting step in steroid biosynthesis is the conversion of cholesterol to pregnenolone (Fig. 60.1). 

D. In addition to its abihty to block steroid biosynthesis, ketoconazole is frequently used as an antifungal agent. Its action is readily reversible and is used principally for interim management of Cushing s disease prior to surgery or radiotherapy. Ketoconazole preferentially blocks the C17,20 lyase reaction that is involved in the synthesis of sex steroids. 

Ghadirian AM, Engelsman F, Dhar V, et al The psychotropic effects of inhibitors of steroid biosynthesis in depressed patients refractory to treatment. Biol Psychiatry 37 369-375, 1995... 

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