Title: Vitamin D: A Review on Metabolism and Regulating Factors (Part I)

Authors: Dr Vishakha S. Patil, Dr Rohini S. Mali, Dr Alpana Moghe

 DOI:  https://dx.doi.org/10.18535/jmscr/v4i12.92

Abstract

Vitamin D although was identified in early years of 20th century as a vital component needed for the treatment of rickets, it remained unexplored for a long period. Key findings in recent years brought Vitamin D again in forefront and now it is considered to be the most important Vitamin. It acts as a hormone and is required by most of the cells of our body.  

Before we discuss its functions one must be aware about the metabolism of Vitamin D. In this Review an attempt is made to provide detailed information on the metabolism and regulating factors of Vitamin D.

Keywords-7-dehydrocholesterol, cholecalciferol , 25 hydroxyvitamin D3 , 1α,25(OH)2D3.

References

1.      McCollum EV, Davis M (1913). The necessity of certain lipids in the diet during growth. J Biol Chem 25:167-231

2.      Mellanby E (1919). An experimental investigation on rickets. Lancet 407-412.

3.      Huldshinsky K (1919). Heilung von rachitis durchkunstlichhohensonne. Deut Med Wochenschr 45:712–713.

4.      Steenbock H (1924). Black fat-soluble Vitamins XVII. The induction of growth-promoting and calcifying properties in a ration by exposure to ultraviolet light. J Biol Chem 61:405–422.

5.      Hess AF, Weinstock M (1924). Antirachitic properties imparted to lettuce and to growing wheat by ultraviolet irradiation. Proc Soc Exp Biol Med 22:5–6.

6.      Askew FA, Bourdillon RB, Bruce HM, Jenkins, Webster TA (1931) The distillation of Vitamin D. Proc R Soc Lond 8107: 76-90.

7.      Windaus A, Schenck F, Von Werder F, Uber Das (1936). Antirachitisch wirksome Bestrah lungs-Produktaus 7-dehydrocholesterin. (Concerning the antirachitic activity of the irradiation product of 7 dehydrocholesterol) Hoppe-Seyler’s Z Physiol Chem 241: 100-3(In German).

8.      Lund J, DeLuca HF (1966). Biologically active metabolite of Vitamin D3 from bone, liver and blood serum. J Lipid Res 7: 739-44.

9.      Morri H, Lund, J, Neville PF, DeLuca H.F (1967). Biological activity of a Vitamin D metabolite. Arch Biochem Biophy 120: 508-12.

10.  Blunt JW, DeLuca HF, Schnoes HK (1969). 25 Hydroxycholecalciferol: A Biologically active metabolite of Vitamin D3. Biochemistry 8: 671-5.

11.  Holick MF, Schnoes HK, DeLuca H, Suda T, Cousins RJ (1971). Isolation and Identification of 1,25 dihydroxychole-calciferol- A metabolite of Vitamin D active in Intestine. Biochemistry 10: 2799-804.

12.  Semmeler EJ, Holick MF, Schoes HK, DeLuca HF (1972). The  synthesis of 1α 25 dihydroxycholecalciferol : A metabolically active form of Vitamin D3. Tetrahedron Lett 40: 4147- 50.

13.  Lawson DE and Wilson PW (1974). Intranuclear localization and receptor proteins for 1,25dihydroxycholecalciferol in chick intestine. Biochem J 144(3): 573-583.

14.  Brumbaugh PF and Haussler MR (1975). Specific binding of  1alpha,25-dihydroxycholecalciferolto nuclear components of chick intestine. J Biol Chem 250(4): 1588-1594.

15.  Holick MF, MacLaughlin JA, Clark MB, et al (1980). Photosynthesis Of previtamin D3 in human skin and the physiologic consequences. Science 210: 203-5.

16.  Webb AR, Decosta BR, Holick MF (1989). Sunlight regulates the cutaneous production of Vitamin D3 by causing its photodegradation. J Clin Endocrinol Metab 68: 882-7.

17.  Chun RF, Adams JS, Hewison M (2008). Back to the future: A   new look at ‘old’ vitamin D. J Endocrinol 198: 261–269.

18.  Hollis BW (1997). Detection of Vitamin D and its major metabolites. In: Vitamin D, edited by D. Feldman FH, Glorieux and Pike JW, San Diego CA: Academic 587–606.

19.  Jones G (2008). Pharmacokinetics of Vitamin D toxicity. Am J  Clin Nutr 88(2): 582S -586.

20.  Cooke NE and Haddad JG (1989). Vitamin D Binding Protein (Gc-Globulin). Endoc Rev 10(3): 294-307.

21.  Haddad JG (1995). Plasma Vitamin D-binding protein (Gc-Globulin): Multiple  tasks. J Steroid Biochem Mol Biol 53(1-6): 579-582.

22.  Shinki T, Hin CH, Nishimura A, Nagai Y, Ohyama Y, Noshiro M et al (1992). Parathyroid hormone inhibits 25-Hydroxyvitamin D3-24-Hydroxylase mRNA Expression stimulated by 1α,25- Dihydroxyvitamin D3 in rat kidney but not in intestine. J. Biol.Chem 267:13757–13762. 

23.  Kogawa M, Anderson PH, Findlay DM et al (2010).The metabolism of 25(OH) Vitamin D3 by osteoclasts and their precursors regulates the differentiation of osteoclasts. J Steroid Biochem Mol Biol 121(1-2): 277-280.

24.  Holick MF and Bikle DD (2010). Extrarenal  Synthesis of 1,25-Dihydroxyvitamin D and Its Health Implications. In Vitamin D, Bendich A,  Editor. Humana Press. 277-295.

25.  Stoffels K, Overbergh L, Giulietti A, et al (2006). Immune Regulation of 25-Hydroxyvitamin-D3-1α-Hydroxylase in Human Monocytes. J Bone Miner Res 21(1): 37- 47.

26.  Hewison M, Burke F, Evans KN et al (2007). Extrarenal 25Hydroxyvitamin D3 1[alpha]- hydroxylase in human health and disease. J Steroid Biochem Mol Biol 103(3-5): 316-321.

27.  Hewison M, Freeman L, Hughes SV, et al (2003).  Differential Regulation of Vitamin D Receptor and Its Ligand in Human Monocyte-DerivedDendritic Cells. J Immunol 170(11): 5382-   5390.

28.  Fritsche J, Mondal K, Ehrnsperger A et al (2003).Regulation of 25-hydroxyvitamin D3-1{alpha}-hydroxylase and production of          1{alpha},25-dihydroxyvitamin D3 by human dendritic cells. Blood 102(9): 3314-3316.

29.  Heine G, Niesner U, Chang HD et al (2008).  1,25-dihydroxyvitamin D(3) promotes IL-10  Production in human B cells. Eur J Immunol  38(8): 2210- 2218

30.  Baeke F, Korf H, Overbergh L et al (2010).  Human T lymphocytes are direct targets of 1,25- dihydroxyvitamin D3 in the immune system. J Steroid Biochem Mol Biol 121(1-2):221-227.

31.  Lehmann B and Meurer M (2003). Extrarenal sites  of calcitriol synthesis: the particular role of the skin. Recent Results Cancer Res 164: 135-145.

32.  Bikle DD, Nemanic MK, Gee E et al  (1986). 1,25-Dihydroxyvitamin D3 production by human keratinocytes. Kinetics and regulation. J Clin  Invest  78(2):557-566.

33.  Tokar E and Webber M (2005).  Chemoprevention of prostate cancer by cholecalciferol (Vitamin D3):25-hydroxylase   (CYP27A1) in human prostate epithelial cells. Clin Exp Metastasis 22(3): p. 265-273.

34.  Flanagan JN, Young MV, Persons KS et al (2006). Vitamin D Metabolism in Human Prostate Cells: Implications for Prostate Cancer Chemoprevention by Vitamin D.Anticancer Res 26(4A): 2567-2572.

35.  Lehmann B and Meurer M (2010). Vitamin D metabolism. Dermatol Ther 23(1): 2-12.

36.  Lehmann B, Genehr T, Knuschke P et al (2001). UVB-Induced Conversion of 7- Dehydrocholesterol to 1,25-Dihydroxy-vitamin D3 in an In Vitro Human Skin Equivalent Model. J Invest Dermatol 117(5): 1179-1185.

37.  Lehmann B, Sauter W, Knuschke P et al (2003). Demonstration of UVB induced synthesis of 1α,25-dihydroxyvitamin D3 (calcitriol) in human skin by microdialysis. Arch Dermatol Res 295(1):24-28.

38.  Brenza HL, DeLuca HF (2000). Regulation of 25 hydroxyvitaminD3 1α hydroxylase gene expression by parathyroid hormone and 1,25 dihydroxyvitamin D3. Arch Biochem Biophys 381:143-52.

39.  Horiuchi N, Suda T, Takahashi H, Shazawa E, Ogata E(1977). In vivo evidence for the intermediary role of 3′, 5′cyclic AMP in parathyroid hormone-induced stimulation of 1α,25- dihydroxyvitamin D3 synthesis in rats.Endocrinology 101: 969-974.

40.  Sherwood LM, Russell J (1989). The role of 1,25-(OH)2D3 in regulating parathyroid gland function. Proc. Soc Exp Biol Med 191:233- 237.

41.  Thakker RV, Fraher LJ, Adami S, Karmali R, O'riordan JLH(1986).Circulating concentrations of 1,25-dihydroxyvitamin D3 in patients with primary hyperparathy-roidism. Bone Miner. Res 1:137-142.

42.  Prosser DE and Jones G (2004) Enzymes involved in the activation and inactivation of Vitamin D. Trends Biochem Sci 29 (12): 664-673.

43.  Chambers TJ, Magnus CJ (1982).  Calcitonin alters behaviour of isolated osteoclasts. J Pathol 136: 27-39.

44.  Shinki T, Uneno Y, DeLuca HF, Suda T (1999). Calcitonin is a major  regulator for the expression of renal 25 hydroxyvitamin D3-1α  hydroxylase gene in normocalcemic rate. Proc Natl Acad Sci 96:8253-8.

45.  Renno T, Krakowski M, Piccirillo C, Lin J, Owens T (1995). TNF- α expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis: Regulation by Th1 cytokines. J.   Immunol. 154:944–953.

46.  Schuster, I (2011). Cytochromes P450 are essential players in the Vitamin D signaling system.     Biochem Biophys Acta 1814(1): 186-199.

47.  Lou YR, Molnar F, Perakyla M et al (2010). 25- Hydroxyvitamin D3 is an agonistic Vitamin D receptor ligand. J  Steroid Biochem  Mol Biol: 118(3):162-170.

48.  Uchida M, Ozono K, and Pike WJ (1994)  Activation of the Human osteocalcin gene by 24R, 25-dihydroxyvitamin D3 occurs through the Vitamin D receptor and the Vitamin D responsive element. J Bone Miner Res: 9(12):1981-1987.

Corresponding Author

Dr Vishakha S. Patil

Dept of Periodontology, Bharati Vidyapeeth Deemed University,

Dental College and Hospital, Pune, India

Email: This email address is being protected from spambots. You need JavaScript enabled to view it.