Vitamin D Flashcards
Can we produce vitamin D
Yes but not to sufficient amounts
What are the vitamin D vitamers? Are they active?
Ergocalciferol (D2)
Cholecalciferol (D3, produced in skin of animals)
Inactive forms and need to undergo metabolism to activate
Vitamin D synthesis
Requires UV light
First 2 steps don’t require enzymes
next steps are all hydrolysis
Up to calcidiol occurs in liver
Next steps occur in kidneys
Describe the photolysis step of vitamin D synthesis
Slow process
Cannot overdose this step because it is reversible
Rate of photolysis is not affected by vitamin D status
Can’t make it in winter
Describe the hydroxylation steps
Two sequential hydroxylations
First occurs in the liver to form calcidiol which is the main circulating form
The second occurs in the kidney to form calcitriol which is the active form of the hormone
Both catalyzed by P450 dependent oxidases
how is vitamin D stored in the body
Vitamin D is not stored in the body, stored as plasma calcidiol and cholecalciferol, half lives of 3 weeks
What is the main route of vitamin D excretion
Bile, undergoes additional reactions prior to bein excreted
How are Cholecalciferol, calcidiol and calcitriol transported in the blood
all bound to vitamin D binding protein (DBP)
40% of cholecalciferol transported in lipoproteins
Regulation of vitamin D metabolism
Main regulation mechanism is through control of 1a hydroxylase and 24-hydroxylase
Major determinant is the availability of calcitriol
T/F factors that increase the activity of one reduce the activity of the other; this allows for rapid activation or inactivation
true
Biochemical functions of vitamin D
Primary role: maintain blood levels of calcium
Also regulates networks of genes in target tissues
How does vitamin D maintain blood levels of calcium (3 ways)? How does vitamin D exert these effects
Enhancing uptake of dietary calcium in small intestine
Reducing excretion in urine by promoting reabsorption in kidney
Mobilizing calcium from bone which accounts for 99% of calcium in body
Acts as a steroid hormone binding to a nuclear receptor which activates gene promoters
What happens when calcitriol binds VDR
a conformational change occurs which allows it to dimerize with RXR, to form the actual transcription factor which
translocates to the nucleus
VDR also undergoes phosphorylation which can modulate its DNA-binding activity. RXR is often bound to sites prior to VDR activation, thus may “mark” genes to be activated.
Describe intestinal calcium absorption (2 phases)?
Administration of calcitriol to intestinal mucosal cells leads to enhanced calcium uptake in two distinct phases:
a rapid response due to recruitment of calcium transporters to the cell surface, and a slower prolonged response due to induced expression of calbindin, a calcium binding protein
What is calbindin
Binds 4 calcium ions and acts as a free calcium buffer and sensor
present in other cells as it may prevent free radicals
What are the non-genomic effects of vitamin D
Binds VDR on cell surface to induce a signaling mechanism which is rapid for the recruitment of Ca transporters from interior surfaces to increase Ca uptake
Fast response
Describe the renal calcium reabsorption
almost all calcium is reabsorbed by kidney and it involves the induction of calbindin expression by calcitriol
how does vitamin D affect bone metabolism
Bone is a major storage for calcium
Calcitriol promotes resorption (release) of bone calcium; decreases collagen, increases osteopontin (bone remodeling)
Induces expression of osteocalcin
how does infection affect vitamin D
decreases VDR expression
Why do infections inhibit VDR
because VDR promotes antimicrobial production
What happened to the immune cell of VDR ko mice? What does this say about the function of Vitamin D
Increased risk of autoimmune disease
VDR and vit D signaling appears to be important in preventing immune overreaction
What levels of vitamin D is classified a deficiency
below 30nM
what are the two primary disorders associated with vitamin D deficiency
Rickets and osteomalacia
What are nutritional rickets
lack of vitamin D
Bone pain, leg deformites, slowed motor development, and hypocalcemia which is the leading cause of death from rickets
Whenn our bodies lack vit D, PTH increases which mobilizes too much calcium from bones
What is osteomalacia
Rickets in adults and only seen when vit D levels fall below 10 nM
Do vitamin D supplementations work
Not really unless you live in the extreme north, are pregnant, a breast-fed child, are house-bound, or have dark skin
What are some pharmacological potential uses for vit D
Multiple sclerosis
Type 1 diabetes-may be due to effects on immune system
Vitamin D toxicity
weakness, nauseas, diarrhea, abdominal pain, hypercalcemia, kidney stones
Toxicity requires large daily amounts of vit D 500-10000 IU
Persists due to accumulation of vit D in adipose when you do get toxicity
