Dehydrocholesterol, 7-, photochemical reaction

A steroid very closely related structurally to cholesterol is its 7 dehydro derivative 7 Dehydrocholesterol is formed by enzymatic oxidation of cholesterol and has a conju gated diene unit m its B ring 7 Dehydrocholesterol is present m the tissues of the skin where it is transformed to vitamin D3 by a sunlight induced photochemical reaction... 

Vitamin D3, also called cholecalciferol, is normally formed in the skin from 7-dehydrocholesterol in a photochemical reaction driven by the UV component of sunlight (Fig. 10-20). Vitamin D3 is not itself biologically active, but it is converted by enzymes in the liver and kidney to 1,25-dihydroxycholecalciferol, a hormone that regulates calcium uptake in the intestine and calcium levels in kidney and bone. Deficiency of vitamin D... 

Figure 5.23 Chemical structures of 7-dehydrocholesterol and vitamin D. The photochemical reaction is an electrocyclic ring opening...

The chemical structure of vitamin D3 is closely related to its precursor, 7-dehydrocholesterol, from which it is produced by a photochemical reaction. Therefore, vitamin Do is closely related structurally to the four-ring nucleus of steroids derived from the cyclopentanoperhydro-phenanthrene ring system. No vitamin D activity is noticed until the B ring of 7-dehydrocholesterol is opened between C-9 and C-10. Thus, vitamin D3 is a 9,10-seco steroid and its carbon skeleton is numbered accordingly (Scheme I). The important aspects of its chemistry center about the 5,6,7-cis-triene structure. The formula for vitamin D3 is C27H44O and its formula weight is 384.64. 

The other exception is vitamin D3, or chole-calciferol. Assuming adequate sunlight, chole-calciferol is the photochemical product from ultraviolet irradiation of 7-dehydrocholesterol found in our skin. A significant proportion of the world s population produces all of the cholecalciferol it needs from this photochemical reaction. It is true that a photochemical reaction is not a biochemical pathway, but exposure to adequate sunlight does fulfill the requirement for cholecalciferol. As noted in the discussion for this particular substance, the compounds commonly referred to as vitamins Dg and D3 are not normal constituents of most human diets. 

Chemistry. There are two forms of vitamin D, and both are considered biologically equivalent. Irradiation of the major plant sterol, ergosterol, produces ergocalciferol, also known as vitamin Dg (Fig. 8.11).Because they are photochemical reactions and in contrast to enzyme-catalyzed biochemical reactions, the formation of cholecalciferol is not clean. Exposure of human skin to sunlight of295-300 nm converts 7-dehydrocholesterol to provitamin D,. The isomerization to cholecalciferol (vitamin Dg) is heat catalyzed. Continuous exposure to ultraviolet radiation from the sun results in the reversible formation of lumisterol... 

Dehydrocholesterol is present in high concentration in human skin. It undergoes a complex series of photochemical reactions upon exposure to sunlight. 

As a first step in minimizing this unwanted reaction, we notice the crucial fact that the spectra of (1) and (2) (see Fischer, 1978) overlap almost completely, thus precluding the use of specific wavelengths to promote one reaction over the other. The only way to avoid excessive loss of 7-dehydrocholesterol by the wasteful reaction is to arrest the main reaction at a certain conversion, but this reduces the reactor throughput. Thus a second photochemical reaction was developed (Hoffmann-La Roche, 1985) in which the E-form was converted back to the desired Z-form. This so-called E/Z isomerization is carried out with a photosensitizer, as shown in reaction E26.1.2. 

A number of important biochemical reactions are promoted by the adsorption of UV-vis radiation.Vitamin D3, which regulates calcium deposition in bones, is biosynthesized in just such a photochemical reaction. This vitamin is formed when the provitamin, 7-dehydrocholesterol, is carried through fine blood capillaries just beneath the surface of the skin and exposed to sunUgJit. The amount of radiation exposure, which is critical for the regulation of the concentration of this vitamin in the blood stream, is controlled by skin pigmentation and geographic latitude. Thus, the color of human skin is an evolutionary response to control the formation of vitamin D3 via a photochemical reaction. 

When the skin is exposed to the ultraviolet radiation of sunlight, part of the store of 7-dehydrocholesterol undergoes a photochemical reaction in the epidermis and the dermis and forms previtamin Dj. Once previtamin D, is formed in the skin, it undergoes a slow temperature-dependent transformation to vitamin D, which takes at least 3 days to complete. Then, the vitamin D-binding protein transports D, from the skin into the circulation. 

In the skin of animals, 7-dehydrocholesterol is converted to vitamin D, by the reaction sequence that follows. The first step in this process, the conversion of 7-dchy-drocholesterol to pre-cholecalciferol, requires light. This is an electrocyclic reaction and must occur by a conrotatory motion to avoid the formation of a highly strained trans double bond in one of the rings. Conrotation involving three pairs of electrons must occur photochemically to be allowed. 

Figure 4 Photochemical conversion of 7-dehydrocholesterol to vitamin D3 and the side-reaction products lumisterob and tachysterob.

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