LEC 44 Lipid Soluble Vitamins

Question 1

What are the 4 lipid soluble vitamins?

Answer 1

A, D, E, & K

Slide 1

Question 2

What are the requirements to be considered a vitamin?

Answer 2

• Organic compounds distinct from lipids, carbohydrates and proteins
• Natural components of foods (usually in minute quantities)
• Essential for normal physiological function
• Deficiency causes specific syndromes
• Not synthesized by the host in sufficient amounts to meet normal physiological needs

Slide 5

Question 3

How are lipid soluble vitamins carried in the blood to this tissues?

Answer 3

using lipoproteins

namely chylomicrons b/c they come from diet

He said this during lecture

Question 4

Retinol (vit A) is derived from what compound?

Answer 4

beta-carotene

The smaller building unit is called isoprene

Slide 7 & 9

Question 5

How is β-carotene converted to Vitamin A?

Enzymes & Intermediates

Answer 5

1. β-carotene dioxygenase converts β-carotene to Retinaldehyde (Retinal) using bile salts and an O2
2. Retinaldehyde Reductase converts retinaldehyde to Retinol using NADPH

Slides 9 & 10

Question 6

Aside from retinol, retinal can also convert to what?

What does this compound act like?

Answer 6

Retinoic Acid

acts like a steroid hormone

Slide 12

Question 7

In the visual cycle, what enzyme converts trans-Retinal to Δ11-cis-Retinal?

Answer 7

Retinal Isomerase

Slide 13

Question 8

After storage in the tissues, how is vitamin A mobilized in the blood?

Answer 8

using retinol-binding protein (RBP)

From the Brick & slide 14

Question 9

What is the major transport (circulating) & storage form of Vitamin A?

Answer 9

Retinol

Brick & Slide 12

Question 10

How does retinal contribute to the visual cycle?

Answer 10

• a component of rhodopsin, the light-sensing biological pigment in the rods of the retina
• On exposure to light, rhodopsin triggers a G-protein cascade that allows the human eye to sense the amount of light in the environment

Brick

Question 11

What is the cellular retinol binding protein involved in intestinal absorbtion?

Answer 11

CRBP II

Slide 14

Question 12

Which cellular retinoic acid binding proteins are involved in embryogenesis?

Answer 12

CRABP I & II

Slide 14

Question 13

What is promyelocytic leukemia?

Answer 13

• the majority of cases involve a translocation of chromosomes 15 and 17
• genetic fusion of the retinoic acid receptor (RAR) gene to the promyelocytic leukemia (PML) gene
• PML protein is responsible for promoting immature myeloid cells differentiation into more mature cells
• Fusion defeats normal regulation
• Responds to RA treatment

Slide 17

Question 14

How does vitamin A deficiency present?

Answer 14

• Night blindness
• Xerosis (dry conjunctivae)
• Keratomalacia (softening and ulcerations of the cornea)
• Rough scaly skin
• Periosteal overgrowth
• Nephritis
• Fetal death and reabsorption
• Ataxia and increased CSF pressure
• Microcytic, hypochromic anemia

Slide 19

Question 15

How does vitamin A toxicity present?

Answer 15

• Birth defects (neural crest dysfunction)
• Muscle and joint pain
• Alopecia and skin erythemia
• Liver dysfunction
• Stunted growth
• Bone fractures

Slide 21

Question 16

What are 3 things that can happen with the eyes due to vitamin A deficiency?

Answer 16

• Bitot’s Spots
• Xeropthalmia
• Keratomalacia

Slide 22

Question 17

What form of vitamin A is associated with teratogenesis in excess amounts?

Accutane

Answer 17

13-cis-retinoic acid

Slide 23

Question 18

What is the role of Vitamin D?

Answer 18

• Maintains plasma calcium & phosphorous concentrations
• Supports cellular processes, neuromuscular and immune function, & bone ossification
• Enhances calcium & phosphorous absorption from small intestine & mobilization from bone
• Acts like a hormone with receptors and target tissues

Slide 24

Question 19

Where is vitamin D stored?

Answer 19

Liver

Slide 26

Question 20

Vitamin D must undergo what type of reaction to leave the liver?

Answer 20

Hydroxylation

Slide 26

Question 21

What is the circulating form of vitamin D?

Answer 21

25(OH)D3

25-hydroxy Vit D

Slide 26

Question 22

How does Rickett’s occur?

Answer 22

• Inborn error with the 1-alpha-hydroxylase in the kidney
• No production of 1,25(OH)2D3

Slide 27

Question 23

What happens when serum calcium is low?

with regards to vitamin D

Answer 23

• 1,25-(OH)2 D & PTH stimulate calcium release from bone and 1,25-(OH)2 D promotes absorption of calcium in the gut
• PTH tells kidney to make more 1,25-(OH)2 D and to inhibit calcium excretion and to excrete phosphate

Slide 28

Question 24

What happens when serum calcium is high?

Low PTH(Parathyroid) and High CT(calcitonin)

Answer 24

• CT inhibits calcium release from the bone
• decreased calcium absorption in gut
• CT tells kidney to excrete calcium
• decreased PTH tells kidney to make more 24,25(OH)2 D instead of 1,25

Slide 29

Question 25

How does vitamin D regulate genes?

Answer 25

interacts with VDR nuclear receptor in target tisues ## Footnote Slide 30

Question 26

Vitamin D deficiency causes what 3 diseases?

Answer 26

* Rickets * Osteomalacia * Osteoporosis ## Footnote Slide 33

Question 27

What happens with vitamin D toxicity?

Answer 27

* Hypercalcemia * Calcinosis (soft tissue calcification) * Polyuria, headaches, vomiting ## Footnote Slide 37

Question 28

What is the current adult recommendation for vitamin D?

Answer 28

400-600 IU/d ## Footnote Slide 39

Question 29

Why is Vitamin E so important and required for all mamalian cells?

Answer 29

* PROTECTS AGAINST REACTIVE OXYGEN SPECIES * PROTECTS AGAINST CHAIN REACTIONS IN LIPID OXIDATIONS * PROTECTS AGAINST FREE RADICALS FORMED BY IONIZING RADIATIONS ## Footnote Slide 40

Question 30

What other vitamins does vitamin E need to do its job?

Answer 30

Vitamin C & Vitamin B3 | Glutathione is also required ## Footnote Slide 42

Question 31

How does vitamin E deficiency present?

Answer 31

* In infants interventricular hemorrhage * Red cell hemolysis * Myopathies * White muscle disease in lower mammals ## Footnote Slide 43

Question 32

Describe vitamin E toxicity.

Answer 32

* Humans and other animal can tolerate high dosages of Vitamin E with little adverse effect * High doses of vitamin E can interfere with the action of the other lipid soluble vitamins. Increasing the dose of the other vitamins overcomes the interference. ## Footnote Slide 44

Question 33

Where does **vitamin K** come from?

Answer 33

* Synthesized by green plants (phylloquinones) * Synthesized by bacteria including those in the human gut (menaquinones) ## Footnote Slide 45

Question 34

How does Warfarin work?

Answer 34

it inhibits Vitamin K epoxide reductase and Vitamin K Reductase which disrupts formation of Gla residues and in turn the clotting process ## Footnote Slide 47 & 51

Question 35

What does Vitamin K-dependent Carboxylase do?

Answer 35

uses a glutamate residue & vitamin KH2 to produce vitamin K epoxide and a carboxylated prozymogen (γ-carboxyglutamate) ## Footnote Slide 47

Question 36

How do calcium and γ-Carboxyglutamate (Gla) interact to promote clotting?

Answer 36

* Gla is a high affinity calcium chelator * the complex interacts with acidic membrane lipids that fold it into correct structures that are recognized by factors in the clotting pathways | Citrate prevents calcium chelation and is therefore an anticoagulant ## Footnote Slide 49

Question 37

How does vitamin K deficiency present?

Answer 37

* Hemorrhage (trauma-induced; intramuscular, skin ecchymoses, spontaneous GI bleeding) * Especially neonatal hemorrhagic disease ## Footnote Slide 53

Question 38

What are the effects of vitamin K toxicity?

Answer 38

* Liver damage at high doses but not much else * High levels of Vit K make it very difficult to achieve adequate anticoagulation with warfarin ## Footnote Slide 54