ABSTRACT
Introduction ........................................................................................................................ 42
History of Vitamin D .......................................................................................................... 44
Chemistry of Vitamin D Steroids........................................................................................ 46
Structure .......................................................................................................................... 46
Nomenclature .................................................................................................................. 46
Chemical Properties ......................................................................................................... 47
Vitamin D3 (C27H44O) ................................................................................................. 47
Vitamin D2 (C28H44O) ................................................................................................. 47
Isolation of Vitamin D Metabolites................................................................................. 48
Synthesis of Vitamin D.................................................................................................... 48
Photochemical Production ........................................................................................... 48
Chemical Synthesis....................................................................................................... 49
Physiology of Vitamin D..................................................................................................... 51
Introduction..................................................................................................................... 51
Absorption....................................................................................................................... 51
Photochemical Production of Vitamin D3....................................................................... 51
Transport by Vitamin D-Binding Protein........................................................................ 54
Storage of Vitamin D ...................................................................................................... 55
Metabolism of Vitamin D ............................................................................................... 55
25(OH)D3..................................................................................................................... 55
1a,25(OH)2D3 .............................................................................................................. 56 24,25(OH)2D3............................................................................................................... 56
Catabolism and Excretion ............................................................................................... 57
Biochemical Mode of Action............................................................................................... 57
Genomic .......................................................................................................................... 58
Nuclear Receptor ......................................................................................................... 59
VDR Domains ............................................................................................................. 60
X-ray Structure of the VDR ........................................................................................ 61
Comparison of X-ray Structures VDR and DBP and Their Ligands.......................... 61
Calbindin-D ................................................................................................................. 62
Nongenomic Actions of 1a,25(OH)2D3........................................................................... 63 Specific Functions of 1a(OH)2D3........................................................................................ 65
1a,25(OH)2D3 and Mineral Metabolism ......................................................................... 65 Vitamin D in Nonclassical Systems ................................................................................. 67
Immunoregulatory Roles of 1a,25(OH)2D3 .................................................................... 68 Structures of Important Analogs..................................................................................... 69
Biological Assays for Vitamin D Activity ........................................................................... 71
Rat Line Test................................................................................................................... 71
Association of Official Analytical Chemists Chick Assay ............................................... 71
Intestinal Calcium Absorption ........................................................................................ 72
In Vivo Technique ....................................................................................................... 72
In Vitro Technique....................................................................................................... 72
Bone Calcium Mobilization............................................................................................. 73
Growth Rate.................................................................................................................... 73
Radioimmunoassay for Calbindin-D28K.......................................................................... 73
Analytical Procedures for Vitamin D-Related Compounds ................................................ 73
Ultraviolet Absorption .................................................................................................... 74
Colorimetric Methods...................................................................................................... 74
Liquid Chromatography-Mass Spectrometry ................................................................. 74
High-Performance Liquid Chromatography ................................................................... 75
Competitive Binding Assays ............................................................................................ 76
Nutritional Requirements of Vitamin D ............................................................................. 76
Humans ........................................................................................................................... 76
Recommended Dietary Allowance .................................................................................. 77
Animals............................................................................................................................ 77
Food Sources of Vitamin D ................................................................................................ 78
Signs of Vitamin D Deficiency ............................................................................................ 80
Humans ........................................................................................................................... 80
Animals............................................................................................................................ 81
Hypervitaminosis D............................................................................................................. 81
Factors that Influence Vitamin D Status ............................................................................ 82
Disease............................................................................................................................. 82
Intestinal Disorders...................................................................................................... 82
Liver Disorders ............................................................................................................ 82
Renal Disorders ........................................................................................................... 84
Parathyroid Disorders.................................................................................................. 84
Genetics ........................................................................................................................... 84
Drugs ............................................................................................................................... 85
Alcohol ............................................................................................................................ 85
Age................................................................................................................................... 85
Sex Differences ................................................................................................................ 85
Efficacy of Pharmacological Doses ..................................................................................... 87
Conclusions ......................................................................................................................... 87
References ........................................................................................................................... 88
The generic term vitamin D designates a group of chemically related compounds that possess
antirachitic activity. The two most prominent members of this group are vitamin D2 (ergo-
calciferol) and vitamin D3 (cholecalciferol). Vitamin D2 is derived from a common plant
steroid, ergosterol, and is the form that was employed for nutritional vitamin D fortification
of foods from the 1940s to 1960s. Vitamin D3 is the form of vitamin D obtained when radiant
energy from the sun strikes the skin and converts the precursor 7-dehydrocholesterol. Since
the body is capable of producing vitamin D3, vitamin D does not meet the classical definition
of a vitamin. A more accurate description of vitamin D is that it is a prohormone; thus,
vitamin D is metabolized to a biologically active form that functions as a steroid hormone
[1,2]. However, since vitamin D was first recognized as an essential nutrient, it has historically
been classified among the lipid-soluble vitamins. Even today it is thought of by many as a
of Vitamins,
vitamin for public health reasons [3], although it is now known that there exists a vitamin D
endocrine system that generates the steroid hormone 1a,25-dihydroxyvitamin D3 [1a,25(OH)2D3] [4].
