Not essential since body can synthesize it

Steroid hormone and Fat soluable Vitamin

-liver, beef, eggs

-some salt water fish

-fortified oj/milk

100 IU/ cup

Destroyed by external factors?

forms of vitamin D from exogenous sources

Not destroyed by cooking, processing, storage

plant vitamin: Vitamin d2 ergocalciferol

animal: vitamin D3 cholecalciferol

Synthesized in sebaceous glands

present in epidermal and dermal layer

1. in glands, cholesterol converts to 7 dehydrocholesterol by 7 dehydrocholestrol reductase

2. When sun hits skin, it converts 7 dehydrocholesterol to precholecaliferol

3. The unstable precholecalciferol rearranges to cholecalciferol

In enters to blood from the skin and is transported by Vitamin D binding protein (DBP) (transthyretin- which is synthesized in the liver)

-absorbed from a micelle, in association with fat and aid of bile salts

-passive diffusion into intestinal cell

-50% dietary vitamin d3 absorbed

-rate is fastest in duodenum, but largest amount of vit d is absorbed in distal small intestine

Vit d is incorporated primarily into chlymicrons, which then enter lymphatic system with subsequent entry into blood

Transport in blood

from digestive tract vs. from sunlight

Digestive tract

In blood, 40% is transported by chylomicrons

-some vit d may be transferred from chylomicron to DBP for delivery to extrahepatic tissues.

-Chylomicron reminants deliver vit d to liver

SUNLIGHT

Cholecalciferol (from skin to blood) in picked up by DBP.

-60% of plasma cholecalciferol is bound to DBP for transport (it then travels primarily to the liver but may go to other tissues like muscle and adipose before hepatic uptake)

Cholecaliciferol (Vitamin D3) gets hydroxylated by 25 hydroxylase (NADPH dep/more active when have low vit D)  to form 25-OH cholecalciferol/D3 (Calcidiol)

Calidiol releases into blood (main form in blood)

Calcidiol transported by DBP is then taken up by kidney(the DBP/calcidiol complex binds to megalin on PM of kindey and is transported into renal cells) and it is hydroxylated by 1-hydroxylase (NADPH dep) to form calcitriol (1,25-(OH)2 cholecalciferol

calitriol is then released from kidney into blood for transport by DBP (loose bind)

On reaching target tissues, calcitriol releases from DBP and binds to Vitamin D receptor (VDR)

target tissues: intestine, bone, kidney, cardiac muscle, beta cells, brain skin, etc.

Calcitriol functions

1. Calcium Homeostasis

a. increases [ ] of calbindin, the more Calbindin with Ca = more Ca bound and absorbed

b. increases expression of TRP (transient receptor potential) - special channelt hat faciliates entry of Ca into enterocyte

c. On BL membrance, Vit D increases activity of Ca-Mg ATPase Pump

calcitriol-VDR complex is phosphorylated and then binds with reinoid X or retinoic acid receptors (RXR/RAR) to form a heterodimeric complex.

the VDR portion of the complex interacts with Vitamin D response elements (VDRE), found in the promotor region regions of specific target genes coding for proteins...

this turns on transcription!

Calcitriol synthesis is stimulated in response changes to changes in blood ca levels and release of pth

HYPOCALCEMIA - low blood calcium inities PTH secretion which then stimulates 1-hydroxylase to convert calcidiol to calcitriol in kidney.

Calcitriol alone or with PTH can then cause serum Ca [] to rise by targeting tissues such as intestine, kidney and bone.

1. Calcitriol enters and binds to VDR

2. This complex moves into nucleus and turns on transcription of Calbindin (makes Calbindin mRNA)

3. Calbindin mRNA enters cytosol and travels to ER for translation into protein calbindin.

4. Calbindin then goes to brush border to faciliate Ca absorption

5. Ca enters enterocyte thru TRP channel and calbindin transportation

6. Ca effluxes from cell into blood via active transport (CA-Mg Atpase pump)

PTH alone or with Calcitriol can direct mobilization of calcium and phosphorus from bone to help acheive normal blood calcium [].

PTH or calcitriol interacts with receptors on mature osteoblasts which induces expression of receptor activator of NFkb ligand (RANKL)

RANKL from osteoblasts interects with receptor protein RANK (on cell surface of immature monocytic osteoclast precursors, called preosteoclasts) and stimulates production and maturation of osteoclasts.

Osteoclasts mobilize Ca and phosphorus from bone by releasing substances that degrade bone matrix.

6 mo- 50 years : 5 ug or 200 IU

more older than 50 years of age

why?

decrease fxn of 1 hydroxylase, not as much sun

Infants that are exclusively or partially bfed should recieve 400 IU per day

from birth until weened off, they should consume 1000 ml vit d formula (whole milk)

Deficiency: rickets symptoms

children

-affects mainly children worldwide

Symptoms:

inadequate calcification of bones

growth retardation

misshapen bones and bowing of legs

enlargement of ends of long bones

deformities of ribs, rachitic rosary of rickets (beading at juncture of ribs and cartilages)

deficiency in adults

osteomalacia

-decreased vitamin d results in descreased calcium absorption

-PTH levels are elevated

-promotes bone resorption

-bone matrix is maintained but bone mineralization is reduced

bone pian and osteomalacia (soft bone)

not by sun exposure

-exogenous dietary intake leads to toxicity

- elevates levels of calcidiol

- calcification of soft tissues such as kidney, heart, and blood vessels - calcinosis

UL = 2,000 IU/day

1. intensity of UV rays

2. Time - 10am-3pm is best for conversion

3. Season

4. Duration (10-15 min) but more for dark skin or less for light skin

5. circulating cholesterol levels

6. smog

7. AGE

8. Sunscreen

Plasma Calcidiol!!!

half life of 10 days to 3 weeks