Enzymatic Mechanisms in Steroid Biochemistry

Abstract

This selective review of the present status of steroid biochemistry is con fined largely to consideration of the enzymatic basis of the transformations of steroids. This subject was comprehensively reviewed in 1957 (1). The in tervening years have witnessed considerable progress toward a better under standing of the manner of formation of the truly formidable number and variety of steroids from animal, plant, and microbial sources.Although this review is oriented toward discussion of the effects of en zymes on steroids, there is intense interest in the effects of steroids on enzyme systems and the possible relation of these phenomena to the molecular basis of steroid hormone action. Progress in the understanding of the details of the biosynthesis of both proteins and nucleic acids has made it possible to show that the regulatory influences of a number of hormones may find a common . basis in the control of the synthesis of various specific prot�ins. This control appears to be exerted at least in part on the process of the transcription of genetic information which directs protein synthesis. Many new studies have appeared in this area since the review by Tomkins & Maxwell (2), and excellent comprehensive discussions of this subject have been provided by Williams-Ashman (3, 4, 5), and by the book Actions of Hormones on Molecular Processes, edited by Litwack & Kritchevsky (6). These studies have not yet revealed the precise manner in which steroids modulate protein synthesis.However, it is now abundantly clear that steroid hormones may affect directly the activities of a number of relatively well-defined enzymatic pro cesses in two quite distinct ways: (a) certain steroids can participate in a catalytic manner in hydrogen transport reactions-the chemistry and pos sible physiological significance of these reactions has been reviewed in detail (7,8,9) ; (b) steroids may affect the activities of a number of enzymes in an "allosteric" way (2,5,7,9) , in accordance with the very imaginative pro posal of Monod, Changeux & Jacob (10).It has not been possible to cover all aspects of the enzymology of steroid transformations. Especially to be regretted are omissions of the discussion of contributions to sterol biosynthesis and the discovery of inhibitors which ap pear specifically to interrupt certain stages in the formation of cholesterol 1 The survey of literature pertaining to this review was completed in Decembe r 1964. 2 Studies from the author's laboratory were supported in part by grants from the National Institutes of Health of the United States Public Health Service. 347 Annu. Rev. Biochem. 1965.34:347-380. Downloaded from www.annualreviews.org Access provided by McMaster University on 02/05/15. For personal use only. Quick links to online content Further ANNUAL REVIEWS

On the Properties of the 12alpha-Hydroxylase in Cholic Acid Biosynthesis. Bile Acids and Steroids 198

“…The microsomal fraction of liver, fortified with NADPH, has been shown to catalyze the hydroxylation of steroids, notably steroid hormones, in a number of positions of the steroid nucleus [21]. The present investigation has shown that the same subcellular fraction in the presence of NADPH catalyzes the 12a-hydroxylation of intermediates in the biosynthesis of bile acids.…”

“…The present investigation has shown that the same subcellular fraction in the presence of NADPH catalyzes the 12a-hydroxylation of intermediates in the biosynthesis of bile acids. When examined, the oxygen in the reaction has always been found to be derived from molecular oxygen [21]. In several cases, the mechanism of the reaction has been studied and has been found to be a direct displacement of the hydrogen in the position that is hydroxylated [21].…”

Enzymic Oxidation and Reduction of Cortisol With Bacillus Cereus

“…The achievement of this important microbial transformation has been actively pursued for several years (2,3). Some insight has recently been obtained into the mechanism of the enzymic dehydrogenation of steroids (4,5).…”

Steroids and Steroidases: I. Long-Range Effects and the Preparation of a-Homosteroids

“…However, studies during the past 10 years by several groups have provided evidence regarding sonle of the steps involved in oxygenation (1,2), isoinerization of A5-3-ltetones (2,3), and dehydrogenation (2).…”

“…Studies on the stereocl~einical pathway for A'-dehydrogenation were carried out independently by several nrorlters (2) ; after an elegant series of experiments, Ringold et al (4) \rere able to describe the stereoche~nical pathway for the A'-dehydrogenase of Bacill~ls splzaericzls in terms of the mechanism suinn~arized in Fig. 1, in which A represents an acidic or electropl~ilic binding site a t the active center, and B a basic ainino acid side cl~ain.…”