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26 Cards in this Set

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What is Vitamin D known as?

Calciferol

What is Vitamin D a generic descriptor for?

It is a genericdescriptor for steroids exhibiting qualitatively the biological activity ofcholecaliferol (Vitamin D3).

What is the structure of Vitamin D?

Structurally, Vitamin Dis a seco-steroid because one of its four rings is broken, while the other three are intact.

How can Vitamin D be obtained?

Vitamin D can beobtained exogenously (by diet) or by endogenous production.

What is important about the endogenous production of Vitamin D?

Endogenous productioncan fully supply the required amounts of Vitamin D, provided that the skin isregularly exposed to sunlight (UVB light).

How is Vitamin D a hormone?

Vitamin D is a hormonebecause it is produced in one part of the body and regulates various physiologicalprocesses in other parts of the body.

What are the two major forms of calciferol?

VitaminD2-Ergocalciferol


Vitamin D3- Cholecalciferol

Where is Vitamin D2- Ergocalciferol found?

Isin plant foods- plants have no cholesterol- so cannot make Vitamin D3.



VitaminD2-Ergocaliferol is largely human made and also added to foods.

Where is Vitamin D3- Cholecalciferol found?

Ismade in the skin of humans with exposure to UVB photons form visible sunlight.




Underthe skin you have a steroid called 7-dehydrocholesterol.


Afterexposure to UVB photons from sunlight, which breaks the ring in this steroid,forming the steco-steroid, forming provitamin D3.


Provitamin D3 will then turn into Vitamin D3.




Isalso consumed in the diet via the intake of animal-based foods.


Animalshave cholesterol so it is the precursor to it.

So which forms of Vitamin D can be obtained by the diet?

D2 and D3

Does dietary vitamin D need to be digested prior to absorption?

No

How is Dietary Vitamin D (D2 + D3) absorbed from intestinal lumen into the enterocyte?

50% of the dietaryvitamin D is absorbed and it occurs in association with fat.

Within the enterocyte, what is Dietary Vitamin D (D2 + D3) incorporated into?

Within the enterocyte, VitaminD is incorporated primarily into chylomicrons, which then enter the lymphaticsystem and then bloodstream.




40% of Vitamin D (Exogenous D2and D3) is found in chylomicrons.

Where does the Dietary Vitamin D (D2 +D3) go to once they are in the chylomicrons?

Adipose tissue andmuscle, among other tissues, take up Vitamin D from chylomicrons and theremainder is delivered to the liver by chylomicron remnants.

Once Vitamin D3 is made from the skin, what is it's fate?

From skin, it slowlydiffuses into blood and is transported by Vitamin D binding protein (DBP),which is made by the liver.




60% of Vitamin D (Endogenous D3)in plasma is bound to DBP for transport.

Where does the Endogenous Vitamin D (D3) go to once they are bound to DBP?

Just like Vitamin D inchylomicrons, the Vitamin D3 bound to DBP is delivered primarily tothe liver but may be picked up by other tissues, especially muscle and adiposetissue, before hepatic uptake.

So Vitamin D travelling in chylomicron (D2 + D3) and DBP (D3) must be activated prior to being used by cells of the body.




How does this activation occur?

D2and D3, found in their respective transporters, are inactive untilthey undergo two enzymatic hydroxylation reactions.




(1)In liver, 25-hydroxylase makes 25-hydroxyvitamin D (25-OHD).




(2)In kidney, 1-alpha-hydroylase, converts 25-OHD into (1,25-OHD) 1,25-drihydroxyvitamin D (calcitriol- the active form of Vitamin D).




Muchof the calcitriol that is made in the kidneys is ultimately released into theblood for other tissue use.

What are the effects of calcitriol?

Whenactivated, DBP transports calcitriol to tissues, and D2 and D3exhibit the same response in the body, including the potency related to theability to cure vitamin D deficiency.




Calcitriolcan then stimulate calcium absorption by the intestine and mobilization ofcalcium (resorption) from bones- latter effect occurs in combination with PTH.

What is Vitamin D sometimes called?

Sunshine vitamin

How is Vitamin D found?

Vitamin D is associated with growth and bonestrength- because it was discovered a fat-soluble factor D obtained from thediet or by body exposure to UV light could prevent rickets (a childhood disease characterized by impaired bonemineralization and development.

How much Vitamin D do we need?

Dietaryintake of vitamin D is only needed for those who do not get enough sunexposure.




Itis hard to know how much sun exposure to get.




Thisis b/c the level of endogenous synthesis influenced by a number of factorslike: season of the year, skin pigmentation, latitude, use of sunscreen,clothing, amount of skin exposure.




Ageis also a factor- since synthesis of Vitamin D declines with increasing age,due in part to a fall in 7-dehydrocholesterol levels and to alterations in skinmorphology. Peopleshould get 10-15 min everyday outside with at least arms and face exposure tosunlight.




Thatrecommendation is for people with lighter skin, but the necessary exposure timefor people with darker skin increases if you are darker.




Thisrecommendation is feasible in places where the temp does not fall belowfreezing for long period of time during the winter.




Thisis not the case in most Canadian cities, because it is so cold all the time andwe are covering up, so people must rely on a steady supply of Vitamin D.




Somescientists say RDA should increase based on relatively poor vitamin D status ofmany people of all ages and skin color, as well as lack of sun exposure due tofear of skin cancer- but RDA has not changed.




HealthCanada says you should have a supplement of Vitamin D if you are over 50 yearsold.

How does calcitriol regulate the availability of calcium in the body?

Non-genomic mechanism




Genomic mechanism

How does the Non-genomic mechanism work?

Thisis done by the activation of signal transduction pathways or intracellularsignaling linked to cell membranes.




Mediatedby binding of calcitriol to cell membrane receptors in selected tissues- mainlyintestine, parathyroid gland, liver, and pancreatic B-cells.§ Thistriggers cellular responses within minutes or seconds.




Onesuch vitamin membrane receptor that has been identified and linked with thesenongenomic actions of Vitamin D is known as membrane-associated rapid responsesteroid binding (MARRS) protein.




Itleads to a rapid increase in calcium uptake in enterocytes, osteoblasts,adipocytes and skeletal muscles."

How does the genomic mechanism work?

Calcitriolalso exerts its functions through genomic mechanisms of action and thusregulates gene expression.




Calcitrioldiffuses from the cytosol into the nucleus, where it binds to nuclear vitamin Dreceptors (VDR).




VDRusually exists as a heterodimer with another receptor (retinoid X receptor,RXR).




Theseheterodimers associate with specific DNA sequences called Vitamin D responsiveelements (VDRE) found in the promoter regions of target genes.




Then,calcitriol regulates the express of several proteins involved in calciumhomeostasis, phosphorus homeostasis, cell proliferation/differentiation andgrowth.

Symptoms of Vitamin D deficiency:

Rickets in children, osteomalcia (soft bones), and osteoperosis in adults

Symptoms of Vitamin D toxicity:

Elevated levels ofcalcium in the blood (hypercalcemia), causes weakness, loss of appetite,diarrhea, mental confusion, vomiting, formation of calcium deposits in softtissues (e.g. kidneys, liver, and heart).