Vitamin D

Question 1

Difference between D2 and D3

Answer 1

D2 has an extra methyl group and double bond. Also their binding is different.

Question 2

Summary of DRI of VD`

Answer 2

• From endogenous production of D3 in epidermis
• Regulated – can shunt previtamin D3 into other metabolites
• From exogenous intake of either;
• D2 or D3
• Not regulated
• Both absorbed and available for hydroxylation / activation
• D2 and D3 have differences in their structure
• Dietary D absorbed bound to chylomicrons / endogenous exported from skin bound to DBP

Question 3

Key Cytochrome P450 Enzymes (CYP)

Answer 3

Vitamin D2 /D3 converts to 25(OH)D: CYP2R1 and CYP27A1

25(OH)D converts to 1,25(OH)2D: CYP27B1

25(OH)D converts to 24,25(OH)2D: CYP24A1

DNA methylation of CYP24A1 in placenta thought to occur during pregnancy to maintain high calcitriol

Question 4

DBP

Answer 4

• Vitamin D is lipophilic – need carrier protein
• DBP-25(OH)D3 is reabsorbed in the proximal tubules of the kidney by the endocytic receptor megalin(***); preventing the urinary loss of this compound and preserving it for hydroxylation
• megalin - on luminal surface of the PCT

Question 5

KO of megalin and DBP

Answer 5

DBP- low 25D and 1,25 D

Megalin- deficiency and bone disease

• urinary loss of lipophilic vitamins
• Very fatal

Question 6

Rickets

Answer 6

is a disorder of dysfunctional bone mineralization.

• VD deficiency
• Ca deficiency
• P deficiency
• Genetic disorders

Question 7

VDR Mutation

Answer 7

Type 1 - defect in 1 alpha HOase
- treat with active hormone
Type 2 - defect in hormone interaction
- treat with ca and p

Question 8

VDRR (Hereditary vitamin D-resistant rickets)

Answer 8

check summary