Vitamins D, biosynthesis

Squalene takes part in metabolism as precursor for synthesis of steroids and structurally quite similar to (3-carotene, coenzyme qlO, vitamins Ki, E, and D. The squalene in skin and fat tissue comes from endogenous cholesterol synthesis as well as dietary resources in people who consume high amounts of olive and fish oil especially shark liver (Gershbein and Singh, 1969). Squalene is synthesized by squalene synthase which converts two units of farnesyl pyrophosphate, direct precursor for terpenes and steroids, into squalene. As a secosteroid, vitamin D biosynthesis is also regulated by squalene. Moreover, being precursor for each steroid family makes squalene a crucial component of the body. 

By contrast, the retro electrocyclization by photochemical irradiation is well known. For example, the photochemical transformation (6e conrotato ring opening) of provitamin D (5) to previtamin D (3) and then thermal isomerization (1,7-H shift) of the latter is a well-established sequence leading to vitamin D (4). It is a sequence involved in vitamin D biosynthesis and in the laboratory synthesis of vitamin D. Moreover, the process is used commercially. 

W. L. Miller and A. A. Portale Genetic disorders of vitamin D biosynthesis. Pediatric Endocrinology 28, 825 (1999). 

Loomis, W. F. Skin pigment regulation of vitamin D biosynthesis in man. Science 156, 501-506 (1967)... 

Adult males, evaluated in winter and summer Bone Pb levels versus decreased vitamin D biosynthesis PbB levels higher in winter, attributed to higher bone Pb resorption due to lower vitamin D formation Oliveira et al. (2002)... 

Valonia, cellulose, 326, 329-330 Vitamin B6, biosynthesis, 1-deoxy-D-threo-pentulose in, 287 Vitamin C... 

DellaPenna, D., Last, R. L. (2006). Progress in the dissection and manipulation of plant vitamin E biosynthesis. 

Cholesterol is a soft waxy substance that is a steroidal alcohol or sterol. It is the most abundant steroid in the human body and is a component of every cell. Cholesterol is essential to life and most animals and many plants contain this compound. Cholesterol biosynthesis occurs primarily in the liver, but it may be produced in other organs. A number of other substances are synthesized from cholesterol including vitamin D, steroid hormones (including the sex hormones), and bile salts. Cholesterol resides mainly in cell membranes. 

Vitamin D is obtained in the diet or by photolysis of 7-dehydrocholesterol in skin exposed to sunlight. Calcitriol works in concert with parathyroid hormone in Ca2+ homeostasis, regulating [Ca2+] in the blood and the balance between Ca2+ deposition and Ca2+ mobilization from bone. Acting through nuclear receptors, calcitriol activates the synthesis of an intestinal Ca2+-binding protein essential for uptake of dietary Ca2+. Inadequate dietary vitamin D or defects in the biosynthesis of calcitriol result in serious diseases such as rickets, in which bones are weak and malformed (see Fig. 10-20b). 

UVB, between 290 and 330 nm, is the deeper region of biotic , that is biologically beneficial, UV radiation. Light of this wavelength region is used for the biosynthesis of vitamin D, and it produces pigmentation of the skin. 

The industrial synthesis of vitamin D is a perfect replica of the biosynthesis which relies on a key photochemical step of electrocyclic ring closure/ring opening (section 5.6). In this case the photochemical process is essential, since the dark reaction is forbidden by reasons of orbital symmetry considerations. 

In the biosynthesis of vitamin D substances, precursors include cholesterol (skin + ultraviolet radiation) in animals ergosterol (algae, yeast + ultraviolet radiation), Intermediates in the biosynthesis include preergocaldferol, tachysterol, and 7-dehydrocholesterol. Provitamins in very small quantities are generated in the leaves, seeds, and shoots of plants. In animals, the production site is the skin. Target tissues in animals are bone, intestine, kidney, and liver. Storage sites in animals are liver and skin. 

Certain human populations depend on dietary sources of vitamin D because of insufficient biosynthesis of the vitamin due to inadequate skin exposure to sunlight. The classic symptoms of vitamin D deficiency are rickets in children and osteomalacia in adults. 25-Hydroxyvitamin D3 is the major circulating metabolite in the blood, but the hormonally active form of the vitamin is 1,25-dihydroxyvitamin D3. The latter metabolite stimulates the intestine to absorb calcium and phosphate by two independent mechanisms and acts with parathyroid hormone to mobilize calcium, accompanied by phosphate, from the bone fluid compartment into the bloodstream. 1,25-dihydroxyvitamin D 3 is also involved in the formation of osteoclasts—giant cells that are solely responsible for the resorption of bone matrix (33). Resorption is an essential process for the development, growth, maintenance, and repair of bone. 

Vitamin D-active substances are required in the diets of growing children and pregnant women, but normal adults receiving sufficient doses of sunshine can manufacture sufficient amounts of these compounds to meet their needs. Active vitamin D compounds can by synthesized in such individuals from 7-dehydro-cholesterol (see Table 6.2), an intermediate in cholesterol biosynthesis. Dietary sources also include cholecalciferol, which is produced from 7-dehydrocholesterol and ergosterol (Table 6.2). 7-Dehydrocholesterol and ergosterol are often referred to as provitamins. 

Figure 6.8 Biosynthesis of biologically active vitamin D compounds from their provitamin precursors.

A hetero Diels-Alder reaction of a precursor 1-9 may be involved in the biosynthesis of the lignane carpanone 1-8 (Fig. 1-3), however, there is no proof for such an assumption [32]. On the other hand, it is well known that pericyclic reactions such as electrocyclic reactions and sigmatropic rearrangements occur in nature e.g. in the biosynthesis of vitamine D, vitamine B12 [33-35] and ecto-carpene [36]. 

A [ 1,7]H shift occurs in the final stages of the human body s synthesis of vitamin D from cholesterol. Here is the last step of the biosynthesis. 

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