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Metabolism Exam 2 > Vitamin D > Flashcards

Vitamin D Flashcards

1
Q

Vit D- General Bill

A

take census. record causes of death for people who died. consumption- tuberculosis- infant mortality high- rickets NEW CAUSE OF DEATH. first time officially recorded- killed 14

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2
Q

Vit D- Morbo puerili Angolorum

A

First scientific examination of rickets. new disease affecting english people.

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3
Q

Vit D- Whistler

A

writes first scientific description of rickets

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4
Q

Vit D- Trousseau

A

recommends cod liver oil as treatment for rickets

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5
Q

Vit D- Mellanby

A

Induces rickets in puppies by feeding a low-fat diet- could be treated with cod liver oil and butter; Vitamin A deficiency*

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6
Q

Vit D- McCollum

A

Shows that heating cod liver oil destroyed xeropthalmic (Vitamin A) activity, but retained antirachitic activity; calls heat stable factor Vitamin D. Vitamin A still cures rickets

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7
Q

Vit D Huldschinksy

A

cures rickets wit UV light lamp

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8
Q

Vit D Two forms

A

D2 and D3

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9
Q

Vit D: Chemistry

A 
Steroid Rings (A, C, D) and an 8 carbon side chain. 
Found in steroid like structures.
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10
Q

Vit D: Synthesis

A

Squalene –> 7-Dehydrocholesterol –> Cholecalciferol (D3). We can make it in our skin. Converts it from dehydrocholesterol in 2 steps with UV lights. All fat soluble vitamins are formed from isoprenoid units.

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11
Q

Vit D: Synthesis in skin

A

Vitamin D enters circulation and binds to DPB (vitamin D binding protein). A lot of other products are formed as well.

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12
Q

Vit D: Food forms: Cholecalciferol (D3) and Ergocalciferol (D2)

A

Cholecalciferol (D3) and Ergocalciferol (D2)

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13
Q

Vit D: cholecalciferol

A

only found in animals *** fish liver and fish oils.

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14
Q

Vit D: Ergocalciferol

A

Plant form, present in only small amounts, common supplement form, less biologically active than D3

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15
Q

Vit D: Food Sources

A

Fish products, cod liver oil, plants have small amount*

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16
Q

Vit D: Fortified foods

A

Milk, orange juice, cereals, yogurts, cheese and infant formula. Only a few countries in Europe fortify (Britain). Finland doesnt because they give cod oil.

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17
Q

Vit D: Absoption

A

Same as vitamin E. As a Micelle into a chylomicron.Does not enter the portal blood circulation. Lymph system: bypasses the liver and drains into general circulation at thoracic duct.

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18
Q

Vit D: Hepatic metabolism

A

Taken up into the liver as a chylomicron. -25-hydroxylase puts the OH at the 25 position Then binds to DBP to leave the hepatocyte into the kidney. Kidney– Hydroxylated again

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19
Q

Vit D: hepatic hydroxylation

A

Catalyzed by 25-hyrdoxylase enzyme in mitochondria. 25-hydroxylase is a cytochrome P450 enzyme. 25-OH D3 is a good indicator of Vitamin D status***. Enzymes use heme iron in active site (cytochrome P450)- class of enzymes in liver.

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20
Q

Renal hydroxylation of 25-OH D3

A

catalyzed by 1-hydroxylase enzyme. Puts -OH group on 1 C position. Active form of vitamin D.

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21
Q

Vit D: 1, 25 (OH)2 D3

A

Also called calcitriol. active form of the vitamin

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22
Q

Vit D: Food vs sun

A

both follow the same path once in the liver

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23
Q

Vit D: factors affecting skin synthesis

A

Sun exposure- more exposure= more vitamin D. – latitude, season, time of day, weather condition, sunscreen. SKIN pigment- dark skinned individuals may require 5-10X more sun exposure to generate same amount of D3 as light skinned individuals. Depends on how much melanin you have, dark skin does not make as much as lighter skin.

24
Q

Vit D: Age and skin synthesis

A

Elderly make less vitamin D from UV light. Elderly at greater risk of deficiency.

25
Vit D: Skin to liver transport
Not known what these compounds do (most are not absorbed and are lost as the skin sloughs off). Research they have health benefits. Different health effects from Vitamin D from sunlight compared to supplements (sunlight may be better).
26
Vit D: Kidney
Kidney has another hydroxylase (24). If it has 24 on it, degraded. 24 can be placed on 25 or 1, 25
27
Vit D: Catabolism of 1, 24, 25- (OH)2 D3
degraded. relevant to excretion soluble in water and secreted in urine.
28
Vit D: plasma transport of 1,25- (OH)2 D3
DBP loosely binds 1,25 (OH)2 D3 to facilitate its release to tissues. Most plsama vitamin D is 25- OH D3. Small amount is 1,25 (OH)2 D3 (active form). 1,25 binds less strongly to go to tissues. binds both at the same time.
29
Vit D Status
Measure 25-OH D3
30
Vit D Active form
1, 25 (OH)2 D3
31
Vit D: Renal 1-hydroxylase
A cytochrome P450 monooxygenase (CYP27PB1). Activity stimulated by: low concentration of 1,25 (OH)2 D3 (feedback inhibition). Low plasma calcium. Low phosphorus intake. Parathyroid hormone (PTH): most potent inducer. stimulates transcription of 1-hydroxylase gene.
32
Vit D: 1, 25-dihydroxyvitamin D3
maintains calcium balance in the body, produced by the kidney.
33
Vit D: 1,25-(OH)2 mechanisms of action
Two main: FUNCTIONS like a hormone-- binds to membrane receptor on target tissues and activates a signal transduction pathway. AFFECTS gene expression- binds to nuclear receptor and affects transcription. Has thousands of different functions in the body.
34
Vit D: 1, 25(OH)2 D3 and Ca2+ homeostasis
Helps to maintain blood calcium by acting on: intestine, kidney and bone. Works with PTH the major regulator of blood calcium***
35
Vit D: Intestine, kidney, bone
Intestine: increases Ca absorption. Kidney: increases Ca re-absorption. Bone: increases Ca mobilization from bone
36
Vit D: Blood Ca homeostasis
Tightly regulated* from 9-11 mg/ 100 mL. REQUIRED for: nerve and muscle cells, blood clotting (too much or too little is bad), enzymes as a cofactor. HYPO/hyper-calcemia can result in death. MAIN purpose is to provide plasma Ca for neuromuscular and nerve function.
37
Vit D: PTH & Calcitriol (1, 25- (OH)2 D3)
Low blood calcium levels are sensed by Parathryoid gland---> releases PTH which acts on the kidney and bone. KIDNEY: retain calcium/ re-absorption. PTH and calcitriol= on one. Calcium and phosphorus from the bone. Stimulates resorption (release) from the bone. Replenishes levels or from the diet
38
Vit D: Calcitriol
Stimulates Ca absorption in intestine
39
Vit D: 1,25 (OH)2 and Ca absorption
Not sure which protein absorbs it. Vitamin D helps it. Enters the Vitamin D receptors. Travel to nucleus . Bind to DNA and cause the transcription of genes involved in calcium homeostasis. Most transcriptionally active as CALBINDIN. The more you have the more you can absorb.
40
Vit D: Calbindin
Binds to Ca and direct its across enterocyte. 1, 25 (OH2) D3 increases transcription. Calbindin expression decreases in Vit D deficiency--- Can lead to rickets.
41
Vit D: Nuclear vitamin D receptor (VDR)
Found in bone, intestine, kidney and skin (aka all cells). Mainly in skin. VDR belongs to superfamily of nuclear receptors, including those for retinoic acid, thyroid and steroid hormones. VDR binds to 1,25 (OH)2 D3 and forms heterodimer with RXR. 1,25 (OH)2 D3-VDR-RXR complex binds to VDRE and stimulates transcription of genes. Hormone example-- also in Vitamin A.
42
Vit D: 1, 25- (OH)2 D3 and gene expression
VDRE changes transcription of genes. Recognizes specific sequences* Vitamin D has a specific receptor in the nucleus. Changes thousands of genes. Effects are all over the body.
43
Vit D: Reabsorption of Ca by kidney
Movement of substances out of renal tube back into the blood
44
Vit D: 1,25 (OH)2 D3 and bone resoprtion
Process by which osteoclasts break down bone and release Ca and P.1,25 (OH)2 D3 stimulates (through osteoblasts) the maturation of osetoclasts.
45
Vit D: osteoclasts
Release HCl and hydrolytic enzymes that dissolve and catabolize bone matrix, releasing Ca and P into the blood
46
Vit D: 1,25 (OH)2 D3: osteoclast maturation
1,25 (OH)2 D3 and PTH induce the expression of receptor activator of RANKL on osteoblast. RANKL interacts with receptor protein RANK on preosteoclast, causing it to mature into osteoclast. All Vitamin D does in this process is helping with maturation of osteoclasts.
47
Vit D: 1,25 (OH)2 D3 and other tissues
Pancreas- increased diabetes risk. Brain- abnormal behavioral changes. Immune cells- autoimmune disease. Skin- Abnormal cell differentiation.
48
Vit. D: 1,25 (OH)2 D3 and pancrease
VDR present. 1,25 (OH)2 D3 essentail for normal insulin secretion* Vitamin D deficient patients have impaired insulin secretion. Mouse model suggest involvement in preventing type 1 diabetes. Observational studies suggest that Vitamin D supplements in infancy and childhood may decrease risk of Type 1.
49
Vit D: 1,25 (OH)2 D3 and the brain
VDR present in the brain- unknown function. VDR knockout mouse model- one symptom is behavioral change. On-going research to understand link between Vitamin D and behavior. -- Human and animal.
50
Vit D: 1,25 (OH)2 D3 and immune
VDR present in hematopoietic cells involved in immune response. Induction of differentiation of precursor cells to monocytes and macrophages. Studies suggest role in "innate" immunity. **Used clinically to treat autoimmune disease.**
51
Vit D: 1,25 (OH)2 D3 and skin cells
Keratinocytes in skin not only are a major source for 7-dehydrocholesterol which can be converted to D3 when exposed to sunlight but also-- keratinocytes have Vit. D receptors and are a "target tissue" for 1,25 D3 -- Interaction of 1,25 D3 and VDR activates the transcription of 1,25 D3 sensitive target genes involved in cell differentiation and proliferation. -- In vitro studies with keratinoyctes incubated 1,25 D3 revealed a marked decrease in DNA synthesis and proliferation .
52
Vit D: Clinical and publish health application
Psoriasis. Osteomalacia/ osteoporosis prevention. Muscle strength- fall prevention. Bone integrity-- fracture prevention older individuals & bone density of fetus and children. Cancer***. Multiple Sclerosis
53
Vitamin D deficiency
Infants and children: rickets-- failure of bone to mineralize. growth retardation. Long bongs of legs bow or knock out. ADULTS: osteomalacia-- dimineralization of bone, resulting from inadequate amounts of Ca and P
54
Vit D: rickets in the US
Recent reports of rickets in the US. Particular problem in African-American breast fed infants. Skin pigmentation reduces UV exposure. ***Lactose intolerance may decrease consumption of Vitamin D- fortified milk. ***
55
Vit D RDA
``` 0-12= 400 19-70= 600 71+= 600 ```
56
Vit D UL
0-6= 1000, 5-12 months= 1500. 1-3= 2500 4-8=3000 9-71+/ preggos= 4000
57
Vit D Toxicity
No risk of Vit D toxicity from sun exposure. Toxicity from oral vitamin D very rare. 10,000 IU per day for several months results in hypercalcemia and calcification of soft tissues.

Metabolism Exam 2 (3 decks)

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