Vitamin D Flashcards
What % of vitamin D in blood is transported by chilomicrons
40
What is cholecalciferol
A form of vitamin D synthesized in the skin
Explain the 3 step process of cholecalciferol starting from the skin
- Cholecalciferol diffuses from skin into blood & is picked up by vitamin D-binding protein (DBP) for transport
- Hydroxylated to 25-OH D3 in liver by CYP-450 hydroxylases
- 25-OH D3 secreted into blood, transported by DBP
What is the main form of vitamin D
25-OH D3 is the main form of vitamin D in the body and reflects vitamin D status
What are normal ranges for serum vit D
25-OH D3 are between 30-40 ng/mL or 75-100 nmol/L
What happens to vitamin D in response to PTH
25-OH D3 is picked up by kidneys
What are the kidneys effect of 25-OH D3
Kidneys hydroxylate 25-OH D3 by 1- hydroxylase (CYP27B1) to form calcitriol
What is the active form of vitamin D
Calcitriol
What is the transporter for calcitriol in the blood
DBP
What are the 2 hormones that regulate calcitriol
PTH and fibroblast-like growth factor (FGF) 23
When is PTH secreted
–Secreted when calcium and phosphorus levels in blood are low
What is the effect of PTH
–Stimulates synthesis of 1-hydroxylase
Where is FGF 23 synthesized
–Secreted by osteocytes and osteoblasts
What is the effect of FGF 23
–Inhibits the synthesis of 1-hydroxylase
How else can 1-hydroxyl are be inhibited
High calcium and phosphorus
What is the main nongenomic function of calcitriol
Serum Calcium homeostasis
What is the mechanism of action of nongenomic calcitriol function
acts by generation of second messengers (MAP kinase, PKC, cAMP, Tyrosine kinase, inositol, etc)
What are the 3 functions of second messengers
–Increase calcium uptake
–Increase intracellular calcium concentration –Increase transcellular calcium flux in enterocytes, osteoblasts, adipocytes, skeletal muscle
What is the main genomic function of calcitriol
Modulation of gene transcription by going to the nucleus of cells
In what 2 ways does calcitriol modulate gene transcription
- Calcitriol diffuses into the nucleus and binds to vitamin D receptors (VDRs)
- Modulation of transcription of genes encoding for proteins related to calcium homeostasis (osteocalcin, osteopontin, 24-hydroxylase, calbindin)
How can calcitriol interact with mRNA
To change translation
Normal serum calcium levels
Normal serum calcium 8.5 to 10.5 mg/dL (2.12–2.62 mmol/L)
What collectively happens when calcium levels are low
–PTH stimulates 1-hydroxylase activity in the kidneys
–Calcitriol increases calcium absorption in the intestine by stimulating expression of calcium channel transporter TRPV6, calbindin D9k and enhances extrusion of Ca across the basolateral membrane of the intestine by stimulating expression of Ca2+ ATPases
–Calcitriol exerts a similar effect in the kidneys by increasing gene expression of TRPV5 and calbindin D28k
In what 2 ways does calcitonin decrease serum calcium
–Blocks calcium and phosphorus mobilization from bones by inhibiting osteoclast activity
–Inhibits tubular resorption of calcium increasing urinary calcium losses
