3. Physiology
        3.12. Renal
            3.12.10. Renal regulation of calcium and phosphate balance
3.12.10.3. Vitamin D

Vitamin D3

[Ref: AV6:chp10; WG21:chp21]

Aka cholecalciferol

Production

Step 1 - Skin

Derived from cholesterol

7-dehydrocholesterol in skin

--> Formation of Vitamine D3 (cholecalciferol) by UV radiation

--> Transport in plasma bound to vitamin D-binding protein (DBP)

Step 2 - Liver

Hydroxylation of vitamine D3

--> 25-hydroxycholecalciferol (aka calcidiol)

Enzyme: 25-hydroxylase

Step 3 - Kidney

Proximal tubular cells hydroxylate 25-hydroxycholecalciferol

--> 1,25-dihydroxycholecalciferol AND 24,25-dihydroxycholecalciferol

Enzyme: 1alpha-hydroxylase and 24-hydroxylase

NB:

1,25-dihydroxycholecalciferol
= Active

24,25-dihydroxycholecalciferol
= Less active

1,25-dihydroxycholecalciferol

aka calcitriol or 1,25-(OH)2D3

Active metabolite

Also produced in the placenta, keratinocytes, macrophages

NB:

Actions

Mechanism of action

Binding of receptor

--> Increased transcription of some mRNA

--> Increase formation of calbindin-D proteins

Calbindin-D proteins

Two types

Increased calbindin-D levels

--> Increased Ca2+ transport

[WG21:p392] Exact mechanism still uncertain

Ca-H ATPase pump

Some evidence that calcitriol increases the number of Ca2+-H+ ATPase pump in intestinal cells

--> Increased transport

Actions

Other actions

Increase synthetic activity of osteoblasts

Necessary for normal calcification of matrix

Probably also stimulates differentiation of immune cells and keratinocytes in skin

 

Regulation

Factors affecting 1,25-dihydroxycholecacliferol formation

Factors increasing formation

Also

NB:

Factors reducing formation



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