BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 8. VITAMINS

8.2. Fat-soluble vitamins

8.2.3. Vitamin D group

Structure and physicochemical properties. The vitamin D group comprises A number of compounds formed upon ultraviolet irradiation of certain unsaturated sterols. The synthesis of sterols proceeds via the oxidation and cyclization of squalene.

Ergocalciferol (vitamin D₂) is formed from ergosterol, which is synthesized in Fungi, whereas cholecalciferol (vitamin D3) is produced from 7-dehydrocholesterol found in the Skin of humans and animals. Ergocalciferol crystallizes from acetone as colorless crystals with a melting point of 120-121 ^oC, and cholecalciferol forms fine needles with a melting point of 84-85 ^oC. Calciferols are thermostable, soluble in fats and organic Solvents, and sensitive to ultraviolet radiation.

Biochemical Functions. Intestinal absorption is mediated by Bile acids. Dietary vitamin is transported following intestinal absorption with the assistance of the transcalciferin protein. Biologically active forms are synthesized in The Liver and Kidneys. During hepatic hydroxylation involving endoplasmic hydroxylase and oxygen, a hydroxyl group is attached to the 25-position of calciferol. This yields the active metabolite, 25-hydroxyvitamin D, which is transported via the Blood

to the kidneys. Hydroxylation at the 1-position, mediated by a specific Ια-hydroxylase and oxygen, produces 1,25-dihydroxycholecalciferol (1,25(OH)зВз), which is the hormone calcitriol (Fig. 8.5). Other vitamin metabolites are also known, notably 24,25(OH)₂B₃. Calcitriol regulates, at the genetic level, the Biosynthesis of Proteins responsible for calcium binding and Absorption in the Small Intestine. Thus, the Functions of the vitamin are mediated through its interaction with specific receptors in the Cytoplasm and Cell Nucleus. Along with two Other Hormones (Parathyroid hormone and Calcitonin), it participates in the Regulation of Calcium and phosphate METABOLISM. The active forms of the hormone function as parathyroid hormone synergists and calcitonin antagonists, maintaining a constant level of Ca²⁺ in the blood. 1,25-dihydroxycalciferol stimulates the intestinal absorption of calcium and phosphate ions via Ca²⁺-ATPase and a calcium-binding protein.

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Fig. 8.5. Scheme of calcitriol synthesis

Requirement and natural occurrence. In cases of insufficient UV exposure of the skin or a lack of vitamin D in the diet, vitamin deficiency develops, leading to Rickets in children and Osteomalacia (bone softening) in adults.

In both instances, the mineralization process (calcium incorporation) of Bone tissue is impaired. Additionally, a condition known as vitamin D-dependent rickets is recognized, in which renal production of 1,25-dihydroxyvitamin D is impaired. Cases of hypervitaminosis have been described, occurring due to the overdose of the vitamin aimed at the rapid Treatment of rickets (manifested by general weakness, polyuria, vomiting, bone pain, and elevated blood pressure). Vitamin status is assessed by measuring the plasma concentration of its primary transport form, 25(OH)D, using a radiocompetent binding assay. Normally, the plasma concentration of 25(OH)D should range between 20-40 ng/mL.

The highest amounts of the vitamin are found in animal-derived products: butter, liver, egg yolks, fish oil, and Yeast. The daily requirement for children ranges from 10-25 mcg (1 mcg = 40 IU) depending on age and physiological state. For adults, it is significantly lower.