Vitamin D
Genomic Mechanism of 1,25 (OH)2 D
travels to nucleus and binds to VRD receptor
1,25 (OH)2D genomic mechanisms
travels to nucleus and binds to receptors (VDR)
Half life of Vit D
up to 3 weeks
T/F. 1, 25 (OH)2 and VDR (VD receptor) is made only in the intestine, kidney, and bone
F
T/F. Vitamin D toxicity can occur with excessive sun exposure
F- body can regulate
T/F. Vitamin D is readily stored in the liver.
F; very little vitamin D is stored in the liver
What you get with a vitamin D deficiency
rickets osteomalacia osteoporosis back hump
When blood calcium is low, in the kidney the presence of PTH does what?
stimulates calcitriol activation
Another source of VD
sunlight
What are the 2 routes that Vitamin D can be transported to the liver?
Dietary vitamin D Cutaneous vitamin D
How does cutaneous vitamin D3 get into the tissues?
Diffuses thru skin, passes thru subcutaneous fat stores, binds to DBP, directly released to tissues
Where is most of the VitD absorbed?
Distal small intestine
Look at figure 10.14
Do it
See figure 10.13
Genomic mechanisms of vitamin D
What happens to 1, 25 (OH)2 Vit D after it is released from the kidney?
Goes to other tissues (esp intestine, bone, muscle)
Where is the majority of Vitamin D found?
In the blood, some found in adipose and muscle tissue
How does Vit D get out of the enterocyte?
Incorporated into a chylomicron
How is VD absorbed?
Incorporated into a micelle with help from fat and bile salts by passive diffusion
What do the increased synthesis of Calbindin D9k and TRPV6 increase?
Increases Ca++ absorption
What does increased alkaline phosphatase activity do?
Increases PO4 (phosphorus) absorption
What does 1,25 (OH)2D do in the intestine?
Increases absorption of Ca++ and PO4 Calbindin D9k synthesis increases TRPV6 synthesis increases Alkaline phosphatase activity increases
What does 1,25 (OH)2D do in the kidney?
Increases re-absorption of Ca++ in kidney tubule Calbindin D28K synthesis increases Increases blood Ca++ concentrations Increases exctretion of PO4
What does P450 Hydroxylase use to convert Vitamin D2/3 to 25-OH Vitamin D?
Iron
______ is needed for Vit D activation aka 1-hydroxylase
Iron
What do the genomic mechanisms of vitamin D affect?
Transcription of vitamin D-regulated genes Activates or represses gene transcription Calcium homeostasis Increases blood concentrations Acts on bone, intestine, and kidney
T/F VD status is lower in areas where sunlight is indirect or weak
True
T/F Vitamin D isn't really a vitamin since it can be made in the body
True
T/F Vitamin D can be fortified in foods
True
In the Dietary Vitamin D route, where is some of the Vitamin D transferred to other than the chylomicron after entering the lymphatic system?
Vitamin D binding protein (DBP)
In the Dietary Vitamin D route, what forms of vitamin D can be incorporated into chylomicrons?
Vitamin D2 or D3
Vulnerable groups for Vit D deficiency
elderly diseases- celiac, cystic fibrosis, bariatric pts, renal disease, obesity
Is most vitamin D excreted through the feces or urine?
feces
What happens after Vitamin D2/3 is made into 25-OH Vitamin D?
gets released into blood
Symptoms of Vitamin D toxicity
hypercalcemia (kidney stones), calcification of soft tissues, anorexia, nausea, vomiting
When blood calcium levels are low, PTH ______ 1-hydroxylase enzyme activity of calcitriol
increases
When blood calcium is low, in the intestine the presence of PTH does what?
increases 1, 25 (OH)2 VD
In the kidney, calcitriol does what?
increases reabsorption of calcium increases calbindin D28K synthesis increases blood Ca++ concentrations
Some potential roles of vitamin D just discovered
insulin action/secretion cancer prevention infection protection reduce blood pressure helps w/ Chrons, diabetes, and MS
Where is most 24-hydroxylase found in the body?
kidney
Plant sources of Vitamin D
mushrooms, yeast, OJ
What does calcitriol in the kidney enhance the excretion of?
phosphorus, so lowers PO4 concentrations
What is the best measure of vitamin D status?
plasma concentrations
What is the active form of Vitamin D?
1, 25 (OH)2 Vitamin D
When 25-OH VitD is taken up by tissues, what form is it converted to?
1, 25 (OH)2 Vitamin D
Calcitriol activates what?
1,25 (OH)2D
Form: 1,25 (OH)2 vitamin D2 or D3 Short Form: Name: Sources:
1,25(OH)2D2 or 1,25(OH)2D3 calcitriol made in kidney
What is the half life of Vitamin D?
1-3 weeks
What is the enzyme that converts 25-OH VitD to the active form?
1-hydroxylase
What is 25-OH Vit D converted to if concentrations are high?
24, 25 (OH)2 Vit D
What is the enzyme that converts 25 (OH)2 Vit D to 24, 25 (OH)2 Vit D?
24-hydroxylase
Form: 25-OH Vitamin D2 or D3 Short Form: Name: Sources:
25(OH)D2 or 25(OH)D3 calcidiol made in liver
Once in the liver, what form does Vitamin D2 or D3 get converted to?
25-OH Vitamin D2 or 25-OH Vitamin D3
What is the half life of 1, 25 (OH)2 Vit D?
4-5 hours
How does 1, 25 (OH)2 D enhance bone Ca++ and PO4 resorption?
Activates cytokine RANK-L which stimulates osteoclasts to eat away at bone
What are the genomic mechanisms of Vitamin D?
Affects transcription of Vitamin D-regulated genes
The activity of P450 Hydroxylase is related to what? More _____ = less activity of enzyme
Amount of substrate, more substrate = less activity of enzyme
Form: Vitamin D2 Short Form: Name: Sources:
D2 ergocalciferol from plants
What form is Vitamin D in of plant origin
D2- ergocalciferol
Form: Vitamin D3 Short Form: Name: Sources:
D3 cholecalciferol isomerization
How does 1, 25 (OH)2 increase the absorption of phosphorus in the intestine?
Because it increases alkaline phosphatase activity
How/why does 1, 25 (OH)2 increase the absorption of calcium in the intestine?
Because it increases the synthesis of TRPV2 and Calbindin D9K
Non-genomic mechanisms (less well known)
Binds to cell surface receptors Activates signal transduction pathways (inc. calcium influx into cell)
What are the non genomic-mechanisms of Vitamin D?
Binds to cell surface receptors Activates signal transduction pathways (like calcium influx into the cell)
Activated 1, 25 (OH)2 in the intestine increases the absorption of what?
Ca++ and PO4
What is another name for the active form of Vitamin D?
Calcitriol
Vitamin D's reactions with other nutrients
Calcium homeostasis Vitamin K in activation of bone forming proteins
What is form of Vitamin D is formed from sunlight
Cholecalciferol, or VD3
What form is Vitamin D in of animal origin
D3- cholecalciferol
What is 25-OH Vitamin D bound to in the blood?
DBP
What has a high affinity to take up VitD from the blood?
Kidney
Where is 1-hydroxylase found in high concentration?
Kidneys
Is 24, 25 (OH)2 Vit D a more or less active form than 25 (OH)2 Vit D?
Less
What does increased kidney excretion of PO4 do?
Lowers blood PO4 concentrations
Is 1, 25 (OH)2 Vit D a good measure of vitamin D status?
Naw
Does dietary VD require digestion?
No
Does dietary Vitamin D require digestion?
No
What is the enzyme converts Vitamin D to 25-OH Vitamin D?
P450 Hydroxylase
Increased calcitrol in the kidney increases what?
PTH, so increased 1,25 (OH)2D activation
What represents the major storage form of Vitamin D?
Plasma 25-OH Vitamin2 or 25-OH Vitamin D3
Why does it bind to DBP?
So it can get to the other tissues
Genes involved in calcium homeostasis
^TRPV6, ^calbindin
What does the 1, 25 (OH)2 complex do?
activates or represses gene transcription helps regulate calcium concentrations
Where is vit D stored?
blood
What tissues does the 1, 25 (OH)2 complex act on?
bone, intestine, and kidney
What is the precursor for VD from sunlight?
cholesterol
Animal sources of Vitamin D
cod liver oil (best), beef, dairy, saltwater fish
1,25 (OH)2 D-VDR genomic mechanisms
complex binds to vitamin D responsive element
1, 25 (OH)2 D-VDR
complex that binds to vitamin D responsive element
Enzyme activity of 1-hydroxylase is ______ by dietary phosphorus
decreased
1, 25 (OH)2 Vit D (end product) _________ 1-hydroxylase enzyme activity
decreases
When is Calcitrol synthesis activated in the kidney?
when blood calcium is low
When is calcitriol activated in the intestine?
when blood calcium is low
