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HUN 4221 Exam 2 > Vitamin D > Flashcards

Vitamin D Flashcards

1
Q

Daniel Whistler

A

Writes the first scientific description of rickets.

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2
Q

Trousseau

A

Recommended cod liver oil as a treatment for rickets

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3
Q

McCollum

A

(discovered vitamin A) heated Vitamin A to destroy activity and discovered vitamin D is treating rickets

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4
Q

Huldschinsky

A

cures rickets with UV light

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5
Q

Adolf Windaus

A

won nobel prize for research of the sterols and their connection with vitamins (cholesterol and vitamin d) discovered three different forms of vitamin but then later realized there is only two

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6
Q

Vitamin D3 chemistry

A

Three steroid rings and an 8-carbon side chain.

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7
Q

What is another name for D3?

A

Cholecalciferol

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8
Q

How does our skin produce cholecalciferol from UV light?

A

From 7-dehydrocholesterol

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9
Q

How is 7-dehydrocholesterol synthesized?

A

From squalene

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10
Q

What is the difference from 7-dehydrocholesterol and cholesterol different?

A

There is a double bond.

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11
Q

How does Vitamin D3 enter blood stream from UV light?

A

7-dehydrocholesterol is converted to cholecalciferol after the skin is exposed to UV light and then D3 is binded to DBP to travel in blood.

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12
Q

What are the food forms of Vitamin D?

A

Cholecalciferol (D3) and Ergocalciferol (D2)

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13
Q

Where is Cholecalciferol (D3) found?

A

Only found in animals (fish liver and fish oils)

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14
Q

Where is Ergocalciferol found (D2)?

A

Found in Plants, present in small amounts,
common supplement form
less biologically active than d3 (but are the same for this exam)

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15
Q

In the U.S. and Canada, what foods are fortified with Vit. D?

A

Milk, yogurts, orange juice, cereals, cheeses, infant formula.

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16
Q

RDA of Vitamin D?

A

600 IU

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17
Q

Why do people in Finland not fortify their food?

A

They make their kids eat cod liver oil.

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18
Q

How can Vitamin D abosorption be reduced in clinical conditions?

A

If the condition reduces fat absorption

cystic fibrosis, celiac, chrons, bypass, medication that reduce cholesterol absorption

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19
Q

How does D3 enter the liver?

A

Transported from the lymph system to hepatocyte through chylomicron.

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20
Q

Where is 25-hydroxlase located and what does it do to D3?

A

In mitochondrial hepatocytes and it adds a hydroxy Whagroup to D3 at the 25 carbon position and converts it to 25-OH D3

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21
Q

What binds to DBP and where and what does it do?

A

25-OH D3 in the hepatocytes and 1, 25- (OH)2 D3 (kidney?) DBO transports these molecules to their designated spots.

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22
Q

How is D3 secreted out of the hepatocyte?

A

Converts to 25-OH (Calcidiol) D3 by 25-Hydroxylase and then binds to DBP and secreted out into the plasma

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23
Q

After 25-OH D3 (Calcidiol) DBP is secreted out of hepatocyte, where does it go?

A

To kidneys for further hydroxlyations

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24
Q

What is 25-Hydroxylase?

A

A cytochrome P450 enzyme

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25
Q

What is the indicator of Vitamin D status?

A

25-OH D3 (Calcidiol)

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26
Q

What are cytochrome P450s?

A

A large family of protein involved in drug metabolism or in vitamin metabolism.

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27
Q

What is 1-hydroxylase and where is it located?

A

It adds a hydroxy group to the first carbon of 25-OH D3 and produces 1, 25- (OH)2 D3 in the renal cells.

28
Q

What is the active form/hormonal form of Vitamin D?

A

Calcitriol or 1, 25- (OH)2 D3

29
Q

What does Calcitriol do?

A

Maintains calcium balance in the body

30
Q

What are factors that affect skin synthesis of D3?

A 
Latitude, season, time of the day, weather conditions, sunscreen, 
skin pigment (need 5-10 x more sun exposure to generate same amount of D3 as light skin individuals
31
Q

At what lattitude are people in danger of Vitamin D def?

A

37 degrees North of the equator and 37 degrees south of the equator
37th parallel

32
Q

When is 24-hydroxylase used and where is it located?

A

It is used when the body has a high amount of Calcitriol so it catabolizes calcitriol to 24,25-(OH)2 Cholecalciferol.

33
Q

The catabolism of 1, 24, 25- (OH)3 D3 produces what?

A

Calcitroic Acid-

34
Q

What is Calcitroic Acid?

A

It is soluble in water and secreted in urine.

35
Q

Why does DBP bind to Calcitriol loosely?

A

Because calcitriol is the active form and needs to be released into the tissues so it facilitates the release into designated tissues

36
Q

What is the transport/ storage form of Vitamin D?

A

25-OH D3 Calcidiol

37
Q

What stimulates the renal 1-hydroxylase activity?

A
  • Low concentration of 1, 25 (OH)2 D3 Calcidiol (feedback inhibition) If there is too much Calcidiol then it stops
  • Low plasma calcium
  • Low phosphorus intake
  • pth
38
Q

What stimulates the transcription of 1-hydroxylase gene?

A

PTH Parathyroid hormone

-the mose potent inducer of 1-hydroxylase

39
Q

PTH responds to what?

A

Low blood calcium

40
Q

What are the two main functions of Calcitriol (1, 25 (OH)2 D3)?

A
  • Functions like a hormone binding to membrane receptors on target tissues and activates a signal transduction pathway
  • Affects gene expression by binding to nuclear receptor and affects transcription
41
Q

What is Calcitriol main job in the body?

A

Maintain blood (Ca2+) levels by acting on the tissues of the intestine (to increase absorption of Ca 2+), kidney (to increase reabsorb of Ca2+), and bone (to increase Ca2+ mobilization from bone)

42
Q

What is the major regulator of blood Ca2+

A

PTH

43
Q

What are the main tissues that participate in Ca2+ homeostasis?

A

Kidney, intestine, bone

44
Q

What is Ca2+ needed for?

A

Nerve and muscle cells, blood clotting, enzymes as a cofactor

45
Q

What is the main purpose of Calcitriol 1, 25-(OH)2 D3 and PTH?

A

To provide plasma Ca2+ for neuromuscular function

46
Q

How is Ca2+ absorbed into the intestine?

A

1, 25- (OH)2 D3 calcitriol enters intestinal cell and binds to VDR and travels to the nucleus

  • In the nucleus it binds to DNA and produces the calbindin mrna
  • mRNA of calbindin enters cytocol and travels to ER to translate in to Calbindin and then travel to the brush border of intestine to bind to calcium and facilitate the absorption of Ca2+
47
Q

What does Calbindin do?

A

It binds to Ca2+ and directs its transports across the enterocyte (intestinal cell)

48
Q

What increases the transcription of Calbindin?

A

1, 25- (OH)2 D3

49
Q

What happens to Calbindin in Vitamin D deficiency?

A

Expression decreases

50
Q

Where is VDR most abundant in?

A

Bone, kidney, intestine, skin

51
Q

What superfamily does VDR belong to?

A

Family of nuclear receptors including those for retinoic acid, thyroid, and steroid hormones such as estrogen or testosterone

52
Q

How does 1, 25- (OH)2 D3 affect gene expression?

A

VDR binds to 1, 25- (OH)2 D3 and forms the heterodimer with RXR (Retionic X receptor)
The 1,25-(OH)2 D3-VDR-RXR complex binds to VDRE (Vitamin D Response Element) and stimulates transcription of genes SUCH AS CALBINDIN (intestine)–> increasing Ca2+ absorption

53
Q

What does VDR bind to?

A

Only to the active form of Vitamin D (1,25-(OH)2 D3

54
Q

Where does reabsorption of Ca2+ take place?

A

In the renal tubule, specifically the glomerulus, where Ca2+ is filtered out of blood into the pro-urine but if needed it will be absorbed right back into the blood so it is not secreted

55
Q

What activates the transcription of TRPV5?

A

PTH and Vitamin D

56
Q

What is TRPV5 and where is it located?

A

A calcium channel that enhances the reabsorption of Ca2+ from the pro-urine and back into the blood and its located in glomerulus

57
Q

What is bone resorption?

A

Process by which osteoclasts break down bone and release Ca2+ and P

58
Q

How is Ca2+ released from bone?

A

1,25-(OH)2 D3 stimulates through the osteoblasts the maturation of osteoclasts
The osteoclasts will release HCL and hydrolytic enzymes that will dissolve and catabolize the bone matrix, releasing Ca2+ and P into the blood.

59
Q

How do Osteoclasts mature due to 1,25(OH)2 D3?

A

1,25-(OH)D3 and PTH induce the expression of RANKL on Osteoblasts
RANKL then interacts with RANK on preosteoclast and matures them in Osteoclasts where Calcification occurs and releases Ca2+ into the blood

60
Q

How is RANKL created?

A

Similar to Calbindin
Calcitriol binds to VDR and then binds to RXR.
-This complex binds to VDRE which then eventually leads to the translation of RANKL

61
Q

What are other tissues that response to 1,25-(OH)2 D3 and could be affected by Vitamin D def?

A

Pancreas- increased diabetes risk
Brain-abnormal behavioral changes
Immune cells- autoimmune disease(used to treat MS, Lupis, rheumatoid arthritis)
Skin- abnormal cell differentiation

62
Q

What is the effect of 1,25(OH)2 D3 in Pancreas?

A

VDRs are present in pancreas and 1,25(OH)2 D3 is essential for normal insulin secretion therefore if Vitamin D deficient, then 1,25 cannot be produced and therefore insulin secretion will be impaired

63
Q

Why are breast fed infants at risk for Type I diabetes?

A

Because breast milk does not have much Vitamin D and may impair insulin secretion later on causing Type I

64
Q

Vitamin D3 Supplements are used for?

A

Psoriasis
Osteomalacia (softening of the bone) /osteoporosis prevention
Muscle strength-fall prevention
Bone integrity- fracture prevention of older individuals, done density of fetus and children
Cancer
MS

65
Q

Vitamin D deficiency can lead to what?

A

Rickets or Osteomalacia (adult form of rickets)

66
Q

Vitamin D toxicity

A

Cannot occur from sun exposure

Very rare in oral Vitamin D but it can cause hypercalcemia and calcification of soft tissues

HUN 4221 Exam 2 (7 decks)

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