Steroids production

Steroids are synthetic products of cholesterol [57-88-5]. The chemical stmcture of a steroid hormone is determined by sequential enzymatic processing of the cholesterol molecule. Steroid products differ among steroid-secreting glands because of differences in enzyme processing, eg, the production of estrogen by the ovary requires enzymatic steps that do not occur in the adrenal cortex. 

There are three general processes that ate used, as of ca 1996, woddwide for steroid production (/) direct isolation from natural sources, (2) partial synthesis from steroid raw materials that have been isolated from plants and animals, and (J) total synthesis from nonsteroidal starting materials (120). 

There are two principal biotechnological appHcations dealing with steroids. Microbial agents are used for processing raw materials into useful intermediates for general steroid production and for specific transformations of steroids to advanced intermediates or finished products (120,145). 

Sobering investigators uncovered a second significant breakthrough in microbial biotechnology of steroid production. They discovered that Corynebacterium simplex converted hydrocortisone (cortisol) (29) to prednisolone via a 1,2-dehydrogenation reaction. This A -3-ketosteroid is a highly active antiinflammatory commercial product (162). 

A third advancement in microbial biotechnology of steroid production was the abiUty to introduce a 16a-hydroxyl group microbiologicaHy (163). Modifications of the liP-hydroxylation, 16a-hydroxylation 1,2-dehydrogenation microbial processes are used for the synthesis of hydrocortisone, prednisolone, triamcinolone, and other steroid pharmaceuticals. A few microbial transformations that have been used to manufacture steroids are Hsted in Table 1 (164). 

Metyrapone is a competitive inhibitor of 11 beta hydroxylation in the adrenal cortex, and effectively inhibits cortisol production. It is used in low doses, titrated to achieve plasma cortisol levels as close as possible to normal day-time values. Occasionally it is used in higher doses combined with replacement corticosteroid treatment. Its main side effects relate to overdosage and resulting hypoadrenalism, but it can also cause hirsutism and hypertension, due to accumulation of precursor steroids. Ketoconazole is also sometimes used to suppress adrenal steroid production, but its potential for hepatotoxicity limits its... 

Adrenal histopathology May indicate alterations in steroid production (corticosteroids, sex steroid precursors)... 

Steroids are important lipids whose structures are based on a tetracyclic system. Most steroids function as hormone chemical messengers, and thus these molecules have been discussed in detail in chapter 5. Structurally, steroids are heavily modified triterpenes that are biosynthesized starting from the acyclic hydrocarbon squalene and progressing through cholesterol to the final steroid product Bloch and Cornforth, who were awarded Nobel Prizes in medicine (1964), contributed greatly to the elucidation of this remarkable biosynthetic transformation. 

The synthesis of adrenal steroids and major excreted metabolites is illustrated in Fig. 5.3.1. Little secreted steroid product is excreted unchanged and most of the catabolism takes place in the liver, although cortisol metabolism by the kidney is clinically important and microbial metabolism in the gut can be quantitatively significant. The major metabolic transformations of hormonal steroids and precursors are detailed by Makin [54] and summarized in Fig. 5.3.2. GC-MS steroid profiling is the technique of choice for measurement of important urinary constituents. 

Optimization of conditions was effected following a two-step process. In the first step, a full-scan spectrum was obtained for each of the steroids. Product-ion spectra at five different collision energies (0.5,1,1.5,2, and 2.5 V) were then obtained for the main precursor ions of the full-scan spectra. Through these studies, candidates were chosen for both precursor and product ions in the MS/MS mode. Once all transitions had been chosen for the MS/MS mode, the final tuning process was carried out... 

Conditions which can affect the immune system and cause it to malfunction are Cushing s disease (caused by excess steroid production or treatment - T and B cell lysis), Hodgkin s disease (cancer of the lymph nodes - whole body T cell deficiency), Bruton s disease (B cell deficiency -susceptibility to infection), and, of course, AIDS (Acquired Immune Deficiency Syndrome). 

FIGURE 21-47 Side-chain cleavage in the synthesis of steroid hormones. Cytochrome P-450 acts as electron carrier in this mixed-function oxidase system that oxidizes adjacent carbons. The process also requires the electron-transferring proteins adrenodoxin and adrenodoxin reductase. This system for cleaving side chains is found in mitochondria of the adrenal cortex, where active steroid production occurs. Pregnenolone is the precursor of all other steroid hormones (see Fig. 21-46). 

A few years later, in 1993, Akermark et al. reported the preparation of imprinted polymers capable of reducing selectively a 3-17-steroidal diketone (21) to the corresponding alcohol with high control of the stereochemistry [13]. The polymers were prepared attaching a polymerisable unit via an ester linkage to the desired steroidal product in position 17 (Fig. 3). The resulting compound was then used as a... 

TG are derived directly from the diet and secreted from the intestines (primarily by way of the lymph) as CM and TRL or synthesized into VLDL in the liver. The net transport of TG is therefore from the intestines and the liver to skeletal and cardiac muscle or to adipose tissue for storage. Cholesterol is used for membrane synthesis and steroid production and is primarily synthesized in extrahepatic tissues. It is continuously transported between the liver, intestines, and extrahepatic tissues, but the net transport of cholesterol is from the extrahepatic tissues to the liver and intestines from where it is eliminated. 

M. J. Walters, R. J. Ayers, and D. J. Brown, Analysis of illegally distributed anabolic steroid productivity by LC with identity com-firmation by mass spectrometry or infrared spectrophotometry, JAOAC, 73 904(1990). 

Endoperoxides derived from cyclohexa-1,3-dienes are the most abundant in this category due to the greater stability compared to their analogues and to the substrate availability [5c,8d]. This subunit is present in a great number of terpene and steroid products. Most of steroid endoperoxides are 5,8-derivatives in which the oxygen bridge has the a-configuration [l,5c,8d]. The steric demand of the methyl at C-10 appears... 

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