Hydroxylation of steroids at carbon 21

Because steroids are lipophilic, they diffuse easily through the cell membranes, and therefore have a very large distribution volume. In their target tissues, steroids are concentrated by an uptake mechanism which relies on their binding to intracellular proteins (or " receptors ", see below). High concentration of steroids are also found in adipose tissue, although this is not a target for hormone action. In the human male, adipose tissue contains aromatase activity, and seems to be the main source of androgen-derived estrogens found in the circulation. But most of the peripheral metabolism occurs in the liver and to some extent in the kidneys, which are the major sites of hormone inactivation and elimination, or catabolism (see below).

The low systemic absorption of topical diclofenac renders overdosage extremely unlikely. However, undesirable effects, similar to those observed following an overdose of diclofenac tablets can be expected if topical diclofenac is inadvertently ingested (1 tube of 100g contains the equivalent of 1000mg diclofenac sodium). In the event of accidental ingestion, resulting in significant systemic side-effects, general therapeutic measures normally adopted to treat poisoning with non-steroidal anti-inflammatory drugs should be used. Gastric decontamination and the use of activated charcoal should be considered, especially within a short time of ingestion.

The quantity of diclofenac absorbed through the skin is proportional to the size of the treated area, and depends on both the total dose applied and the degree of skin hydration. After topical application to approximately 400 cm 2 of skin, the extent of systemic exposure as determined by plasma concentration of Voltarol Emulgel Extra Strength 2% w/w Gel (2 applications/day) was equivalent to diclofenac % gel (4 applications/day). The relative bioavailability of diclofenac (AUC ratio) for Voltarol Emulgel Extra Strength 2% w/w Gel versus tablet was % on day 7 (for equivalent diclofenac sodium dose). Absorption was not modified by a moisture and vapour permeable bandage.

These three reactions are catalyzed by very large, multi-subunit enzymes prolyl 4-hydroxylase , prolyl 3-hydroxylase and lysyl 5-hydroxylase , respectively. These reactions require iron (as well as molecular oxygen and α-ketoglutarate ) to carry out the oxidation, and use ascorbic acid (vitamin C) to return the iron to its oxidized state. Deprivation of ascorbate leads to deficiencies in proline hydroxylation, which leads to less stable collagen, which can manifest itself as the disease scurvy . Since citrus fruits are rich in vitamin C, British sailors were given limes to combat scurvy on long ocean voyages; hence, they were called "limeys". [ citation needed ]

Hydroxylation of steroids at carbon 21

hydroxylation of steroids at carbon 21

These three reactions are catalyzed by very large, multi-subunit enzymes prolyl 4-hydroxylase , prolyl 3-hydroxylase and lysyl 5-hydroxylase , respectively. These reactions require iron (as well as molecular oxygen and α-ketoglutarate ) to carry out the oxidation, and use ascorbic acid (vitamin C) to return the iron to its oxidized state. Deprivation of ascorbate leads to deficiencies in proline hydroxylation, which leads to less stable collagen, which can manifest itself as the disease scurvy . Since citrus fruits are rich in vitamin C, British sailors were given limes to combat scurvy on long ocean voyages; hence, they were called "limeys". [ citation needed ]

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