Vitamin D

Question 1

Can we produce vitamin D

Answer 1

Yes but not to sufficient amounts

Question 2

What are the vitamin D vitamers? Are they active?

Answer 2

Ergocalciferol (D2)
Cholecalciferol (D3, produced in skin of animals)

Inactive forms and need to undergo metabolism to activate

Question 3

Vitamin D synthesis

Answer 3

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

Question 4

Describe the photolysis step of vitamin D synthesis

Answer 4

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

Question 5

Describe the hydroxylation steps

Answer 5

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

Question 6

how is vitamin D stored in the body

Answer 6

Vitamin D is not stored in the body, stored as plasma calcidiol and cholecalciferol, half lives of 3 weeks

Question 7

What is the main route of vitamin D excretion

Answer 7

Bile, undergoes additional reactions prior to bein excreted

Question 8

How are Cholecalciferol, calcidiol and calcitriol transported in the blood

Answer 8

all bound to vitamin D binding protein (DBP)

40% of cholecalciferol transported in lipoproteins

Question 9

Regulation of vitamin D metabolism

Answer 9

Main regulation mechanism is through control of 1a hydroxylase and 24-hydroxylase

Major determinant is the availability of calcitriol

Question 10

T/F factors that increase the activity of one reduce the activity of the other; this allows for rapid activation or inactivation

Answer 10

true

Question 11

Biochemical functions of vitamin D

Answer 11

Primary role: maintain blood levels of calcium

Also regulates networks of genes in target tissues

Question 12

How does vitamin D maintain blood levels of calcium (3 ways)? How does vitamin D exert these effects

Answer 12

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

Question 13

What happens when calcitriol binds VDR

Answer 13

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.

Question 14

Describe intestinal calcium absorption (2 phases)?

Answer 14

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

Question 15

What is calbindin

Answer 15

Binds 4 calcium ions and acts as a free calcium buffer and sensor
present in other cells as it may prevent free radicals

Question 16

What are the non-genomic effects of vitamin D

Answer 16

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

Question 17

Describe the renal calcium reabsorption

Answer 17

almost all calcium is reabsorbed by kidney and it involves the induction of calbindin expression by calcitriol

Question 18

how does vitamin D affect bone metabolism

Answer 18

Bone is a major storage for calcium
Calcitriol promotes resorption (release) of bone calcium; decreases collagen, increases osteopontin (bone remodeling)
Induces expression of osteocalcin

Question 19

how does infection affect vitamin D

Answer 19

decreases VDR expression

Question 20

Why do infections inhibit VDR

Answer 20

because VDR promotes antimicrobial production

Question 21

What happened to the immune cell of VDR ko mice? What does this say about the function of Vitamin D

Answer 21

Increased risk of autoimmune disease
VDR and vit D signaling appears to be important in preventing immune overreaction

Question 22

What levels of vitamin D is classified a deficiency

Answer 22

below 30nM

Question 23

what are the two primary disorders associated with vitamin D deficiency

Answer 23

Rickets and osteomalacia

Question 24

What are nutritional rickets

Answer 24

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

Question 25

What is osteomalacia

Answer 25

Rickets in adults and only seen when vit D levels fall below 10 nM

Question 26

Do vitamin D supplementations work

Answer 26

Not really unless you live in the extreme north, are pregnant, a breast-fed child, are house-bound, or have dark skin

Question 27

What are some pharmacological potential uses for vit D

Answer 27

Multiple sclerosis
Type 1 diabetes-may be due to effects on immune system

Question 28

Vitamin D toxicity

Answer 28

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