Metabolism of steroid hormones ppt

Steroids control the differentiation and proliferation processes of cells and tissues. They participate in the regulation of apoptosis, bone remodelling and neuroregeneration. Severe diseases are caused by monogenic mutations with loss of function of steroid pathway proteins. But defects in steroid metabolism contribute as well to the pathogenesis of many different multifactorial diseases like cancer, diseases of cartilage and bone or neurological diseases. The main focus of the steroid screen is the identification of new animal models for human steroid-related diseases therewith supporting the development of their future medical treatment.

FIGURE 2. Major Pathways of Steroid Biosynthesis.
The pathways outlined here are common to the adrenals, the gonads and, to some extent, to the fetoplacental unit. The first committed step is the conversion of cholesterol to pregnenolone, catalysed by the P-450scc enzyme, which is under pituitary hormone control (ACTH or LH depending on the tissue). Cholesterol side-chain removal is blocked specifically by aminoglutethimide , a steroid biosynthesis inhibitor. From pregnenolone, steroid biosynthesis can proceed either through the so-called "delta-5" pathway (17α-hydroxypregnenolone, dehydroepiandrosterone, testosterone), or through the "delta-4" pathway (progesterone onwards). Progesterone is the starting point for mineralocorticoid synthesis, whereas glucocorticoids are derived from its metabolite, 17α-hydroxyprogesterone. Estrogens are formed from androgens (androstenedione and/or testosterone). Most reactions are irreversible (as denoted by a single arrow). Reversible reactions (double arrows) depend on cofactor availability (. the NADP/NADPH ratio). [Abbreviations used here for the various enzymes are listed in the figure].

As a mitochondrial P450 system, P450c11 is dependent on two electron transfer proteins, adrenodoxin reductase and adrenodoxin that transfer 2 electrons from NADPH to the P450 for each monooxygenase reaction catalyzed by the enzyme. In most respects this process of electron transfer appears similar to that of P450scc system that catalyzes cholesterol side chain cleavage. [9] Similar to P450scc the process of electrons transfer is leaky leading to superoxide production. The rate of electron leakage during metabolism depends on the functional groups of the steroid substrate. [10]

Steroid isolation , depending on context, is the isolation of chemical matter required for chemical structure elucidation, derivitzation or degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but often more [37] or the isolation of "analytical quantities" of the substance of interest (where the focus is on identifying and quantifying the substance (for example, in biological tissue or fluid). The amount isolated depends on the analytical method, but is generally less than one microgram. [38] [ page needed ] The methods of isolation to achieve the two scales of product are distinct, but include extraction , precipitation, adsorption , chromatography , and crystallization . In both cases, the isolated substance is purified to chemical homogeneity; combined separation and analytical methods, such as LC-MS , are chosen to be "orthogonal"—achieving their separations based on distinct modes of interaction between substance and isolating matrix—to detect a single species in the pure sample. Structure determination refers to the methods to determine the chemical structure of an isolated pure steroid, using an evolving array of chemical and physical methods which have included NMR and small-molecule crystallography . [2] :10–19 Methods of analysis overlap both of the above areas, emphasizing analytical methods to determining if a steroid is present in a mixture and determining its quantity. [38]

Metabolism of steroid hormones ppt

metabolism of steroid hormones ppt

Steroid isolation , depending on context, is the isolation of chemical matter required for chemical structure elucidation, derivitzation or degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but often more [37] or the isolation of "analytical quantities" of the substance of interest (where the focus is on identifying and quantifying the substance (for example, in biological tissue or fluid). The amount isolated depends on the analytical method, but is generally less than one microgram. [38] [ page needed ] The methods of isolation to achieve the two scales of product are distinct, but include extraction , precipitation, adsorption , chromatography , and crystallization . In both cases, the isolated substance is purified to chemical homogeneity; combined separation and analytical methods, such as LC-MS , are chosen to be "orthogonal"—achieving their separations based on distinct modes of interaction between substance and isolating matrix—to detect a single species in the pure sample. Structure determination refers to the methods to determine the chemical structure of an isolated pure steroid, using an evolving array of chemical and physical methods which have included NMR and small-molecule crystallography . [2] :10–19 Methods of analysis overlap both of the above areas, emphasizing analytical methods to determining if a steroid is present in a mixture and determining its quantity. [38]

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