Vitamin D
Vitamin D is very important for overall health and well-being. A major source of vitamin D comes from exposure to sunlight. Measurement of 25-hydroxyvitamin D in the blood and not 1,25-dihydroxyvitamin D is used to determine vitamin D status. A blood level of 25-hydroxyvitamin D of at least 20 ng/mL is considered to be vitamin D sufficient. Vitamin D deficiency increases the risk of many common cancers, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and type I diabetes.
Vitamin D is recognized as the sunshine vitamin for good reason. During exposure to sunlight, the ultraviolet B portion of the solar spectrum, with energies between 290 to 315 nm, penetrates into the epidermis. This ultraviolet radiation is absorbed by 7-dehydrocholesterol in the skin, which results in its transformation into previtamin D3 (see Fig. 1). Previtamin D3 is rapidly transformed into vitamin D3 by a temperature-dependent process. Vitamin D3 enters the circulation and is metabolized sequentially first in the liver to 25-hydroxyvitamin D [25(OH)D] and then in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)2D]. Once formed, 1,25(OH)2D interacts with its specific nuclear vitamin D receptor (VDR) in the small intestine to enhance the efficiency of intestinal calcium absorption. It also maintains serum calcium within the normal range by interacting with its VDR in the osteoblast, which results in the expression of receptor activator of NF-κβ ligand (RANKL). This plasma membrane ligand is recognized by its corresponding receptor RANK on the preosteoclast. The intimate interaction between the RANKL on the osteoblast with the preosteoclast's RANK results in signal transduction inducing the preosteoclast to become a mature osteoclast (Fig. 2). The mature osteoclast releases both proteolytic and hydrolytic enzymes and hydrochloric acid to destroy the bone's protein matrix-releasing calcium and other minerals as well as hydrolytic collagen fragments, including N-terminal telopeptide (NTX) and C-terminal peptides (CTX) into the circulation.
(Enlarge Image)
Schematic representation for cutaneous production of vitamin D and its metabolism and regulation for calcium homeostasis and cellular growth. During exposure to sunlight, 7-dehydrocholesterol (7-DHC) in the skin absorbs solar ultraviolet (UVB) radiation and is converted to previtamin D3 (preD3). Once formed, D3 undergoes thermally induced transformation to vitamin D3. Further exposure to sunlight converts preD3 and vitamin D3 to biologically inert photoproducts. Vitamin D coming from the diet or from the skin enters the circulation and is metabolized in the liver by the vitamin D-25-hydroxylase (25-OHase) to 25-hydroxyvitamin D3 [25(OH)D3]. 25(OH)D3 reenters the circulation and is converted in the kidney by the 25-hydroxyvitamin D3-1a-hydroxylase (1-OHase) to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. A variety of factors, including serum phosphorus (Pi) and parathyroid hormone (PTH), regulate the renal production of 1,25(OH)2D. 1,25(OH)2D regulates calcium metabolism through its interaction with its major target tissues, bone and the intestine. 1,25(OH)2D3 also induces its own destruction by enhancing the expression of the 25-hydroxyvitamin D-24-hydroxylase (24-OHase). 25(OH)D is metabolized in other tissues for the purpose of regulation of cellular growth (copyright Michael F. Holick, 2004, used with permission).
(Enlarge Image)
Both 1,25(OH)2D and PTH stimulate the mobilization of calcium from the skeleton by interacting with their respective receptors on osteoblasts, which induces expression of receptor activator of NFkB (RANK) ligand (RANKL). RANK on the immature osteoclast binds to RANKL, which causes it to mature and coalesce with other osteoclast precursors to become mature multinuclear osteoclasts. Osteoclasts digest bone-releasing calcium (Ca) and other minerals as well as hydrolyzed collagen fragments including C-telopeptide (CTX) and N-telopeptide (NTX) (copyright Michael F. Holick, 2004, used with permission).
Vitamin D is very important for overall health and well-being. A major source of vitamin D comes from exposure to sunlight. Measurement of 25-hydroxyvitamin D in the blood and not 1,25-dihydroxyvitamin D is used to determine vitamin D status. A blood level of 25-hydroxyvitamin D of at least 20 ng/mL is considered to be vitamin D sufficient. Vitamin D deficiency increases the risk of many common cancers, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and type I diabetes.
Vitamin D is recognized as the sunshine vitamin for good reason. During exposure to sunlight, the ultraviolet B portion of the solar spectrum, with energies between 290 to 315 nm, penetrates into the epidermis. This ultraviolet radiation is absorbed by 7-dehydrocholesterol in the skin, which results in its transformation into previtamin D3 (see Fig. 1). Previtamin D3 is rapidly transformed into vitamin D3 by a temperature-dependent process. Vitamin D3 enters the circulation and is metabolized sequentially first in the liver to 25-hydroxyvitamin D [25(OH)D] and then in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)2D]. Once formed, 1,25(OH)2D interacts with its specific nuclear vitamin D receptor (VDR) in the small intestine to enhance the efficiency of intestinal calcium absorption. It also maintains serum calcium within the normal range by interacting with its VDR in the osteoblast, which results in the expression of receptor activator of NF-κβ ligand (RANKL). This plasma membrane ligand is recognized by its corresponding receptor RANK on the preosteoclast. The intimate interaction between the RANKL on the osteoblast with the preosteoclast's RANK results in signal transduction inducing the preosteoclast to become a mature osteoclast (Fig. 2). The mature osteoclast releases both proteolytic and hydrolytic enzymes and hydrochloric acid to destroy the bone's protein matrix-releasing calcium and other minerals as well as hydrolytic collagen fragments, including N-terminal telopeptide (NTX) and C-terminal peptides (CTX) into the circulation.
(Enlarge Image)
Schematic representation for cutaneous production of vitamin D and its metabolism and regulation for calcium homeostasis and cellular growth. During exposure to sunlight, 7-dehydrocholesterol (7-DHC) in the skin absorbs solar ultraviolet (UVB) radiation and is converted to previtamin D3 (preD3). Once formed, D3 undergoes thermally induced transformation to vitamin D3. Further exposure to sunlight converts preD3 and vitamin D3 to biologically inert photoproducts. Vitamin D coming from the diet or from the skin enters the circulation and is metabolized in the liver by the vitamin D-25-hydroxylase (25-OHase) to 25-hydroxyvitamin D3 [25(OH)D3]. 25(OH)D3 reenters the circulation and is converted in the kidney by the 25-hydroxyvitamin D3-1a-hydroxylase (1-OHase) to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. A variety of factors, including serum phosphorus (Pi) and parathyroid hormone (PTH), regulate the renal production of 1,25(OH)2D. 1,25(OH)2D regulates calcium metabolism through its interaction with its major target tissues, bone and the intestine. 1,25(OH)2D3 also induces its own destruction by enhancing the expression of the 25-hydroxyvitamin D-24-hydroxylase (24-OHase). 25(OH)D is metabolized in other tissues for the purpose of regulation of cellular growth (copyright Michael F. Holick, 2004, used with permission).
(Enlarge Image)
Both 1,25(OH)2D and PTH stimulate the mobilization of calcium from the skeleton by interacting with their respective receptors on osteoblasts, which induces expression of receptor activator of NFkB (RANK) ligand (RANKL). RANK on the immature osteoclast binds to RANKL, which causes it to mature and coalesce with other osteoclast precursors to become mature multinuclear osteoclasts. Osteoclasts digest bone-releasing calcium (Ca) and other minerals as well as hydrolyzed collagen fragments including C-telopeptide (CTX) and N-telopeptide (NTX) (copyright Michael F. Holick, 2004, used with permission).
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