lecture 18: vitamin D Flashcards
vitamin D
D3 can be synthesized by humans through sunlight on exposed skin
fat-soluble
7-DHC
immediate precursor of cholesterol synthesis, synthesized by skin cells
vitamin D binding protein (VDBP)
major plasma carrier of all vitamin D metabolites
synthesis of vitamin D process
7-DHC in skin absorbs UVB photons
transformation of 7-DHC to previtamin D3
thermal isomerization to vitamin D3
translocation of D3 from skin cells to bloodstream
metabolism of vitamin D in the liver
circulating vitamin D in chylomicron remnants and VDBP-bound are taken up by liver
hydroxylated in liver by 25-OH-ase > 25OHD > circulates in plasma with VDBP, no feedback regulation, best measure of vitamin D status
metabolism of vitamin D in the kidney
25OHD from liver converted to 1,25(OH)2D in the kidneys
megalin
membrane protein that mediates endocytic uptake of 25OHD-VDBP from kidney
1a-hydroxylase
25OHD to 1,25(OH)2D
1,25(OH)2D inhibits 1a-hydroxylase, which inhibits PTH. Therefore, PTH is not inhibited and plasma calcium increases
catabolism of vitamin D
catabolism to more polar and readily excretable inactive metabolites
24-hydroxylation of 25OHD or 1,25(OH)2D via 24-hydroxylase
1,25(OH)2D
biologically active hormonal form of vitamin D
increases efficiency of intestinal phosphorous absorption, maintains calcium levels by activating osteoclasts
acts on intestines, bones, and kidneys to elevate plasma calcium
vitamin D in gene expression
vitamin D binds to VDR> recruited by RXR > heterodimer
heterodimer binds to promoter region of specific genes at VDREs (binding sites)
1,25(OH)2D promotes genes for osteoblasts in bone and CaT1 in small intestine