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Metabolism Exam 2 > Vitamin A > Flashcards

Vitamin A Flashcards

1
Q

Vit A: Wackenroder

A

isolates the orange-yellow pigments from carrots and names it carotene

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2
Q

Vit A: Snell

A

cures blindness by using cod liver oil

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3
Q

Vit A: McColllum

A

studies rats fed purified diets; finds that a “fat soluble A” factor is required for growth; factor is in cod liver oil and butter.

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4
Q

Vit A: Paul Karrer

A

isolates retinol from liver oil

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5
Q

Vit A Chemistry

A

B-ionone ring, isoprenoid unit and a conjugated double bond system. All-trans-retinol

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6
Q

Vit A: 4 more common retinoids

A

All-trans-retinol, Retinal, Retinoic acid, Retinyl ester

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7
Q

Vit A: Interconversion of Retinoids– Retinol

A

Can be oxidized reversibly to retinal– same biological properties

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8
Q

Vit A: Interconversion of retinoids: retinal

A

Can be irreversibly oxidized to retinoic acid– active in growth but not vision or reproduction.

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9
Q

Vit A: Creation of B-carotene

A

B-carotene is a pro-vitamin A. Take 2 vitamin A compounds and combine them to get B-carotene.

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10
Q

Vit A: Carotenoids

A

at least 600 different ones. Responsible for colors in food and leaves changing. Main- alpha, beta and gamma. (difference in the double bond location).

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11
Q

Vit A Definition

A

the generic descriptor for compounds exhibiting the biological activity of retinol (retinoids) and some provitamin A carotenoids.

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12
Q

Vit A Foods

A

Animal foods are the only ones that contain retinol* Non-B carotenoids are in plants only* Both plants and animals contain B-carotene

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13
Q

Vit A Food forms

A

Retinyl-Palmitate– retinol (as all-trans) is typicall bound to fatty acid esters. Retinyl palmitate often bound to protein**
B-carotene are often bound to protein.

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14
Q

Vit A: Absorption (in the lumen)

A

Proteases remove the proteins… Then remove the fatty acids to get free retinol –> Micelles. Retinold binds to CRBPII then puts a fatty acid back on it. Then incorporated into a chylomicron. *** Proteins bound carotenoids –> micelles. B carotene is oxideized to make two retinals then oxidized again to form retinol. Then esterified?

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15
Q

Vit A: absorption

A
  1. cellular retinol-binding protein (CRBP) II binds to both retinol and retinal in the intestinal cell. 2. Retinal, while attached to CRBPII is converted to retinol to form CRBPII retinol. 3. Lecithin retinol acyl transferase (LRAT) esterifies a fatty acid (palmitic acid) onto the CRBPII bound retinol to form CRBPII-retinylpalmitate. 4. Retinyl esters are incorporated along with phospholipids, triacylglycerol, cholesterol esters, carotenoids, and apoproteins to form a chylomicron. 5. Chylomicrons leave the intestinal cell and enter the lymph system and ultimately the blood. 6. Retinoic acid can directly enter the blood where it attaches the albumin for transport to the liver.
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16
Q

Vit A: CRBPII

A

Cellular retinol-binding protein II. abundant in the small intestine. Binds to retinol and retinal making them SOLUBLE.– controls free retinol concentrations and protects it from oxidation. Directs reduction of retinal to retinol– Escorts retinol to LRAT

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17
Q

Vit A: Why does it need to become bound to a protein?

A

Because retinol is fat soluble, can’t float around in water. The protein makes them soluble.

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18
Q

Vit A: LRAT

A

Lecithin retinol acyl transferase. Adds fatty acids (mainly palmitate) to retinol to form retinyl esters. Retinol must be esterified to exit intestinal cell.

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19
Q

Vit A: Why add the fatty acid back on?

A

** From notes: adds fatty acids to retinol In the lumen there are a bunch of enzymes and acid so they just automatically break the retinol esters apart. To be incorporated into a chylomicron, it must have fat.

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20
Q

Vit A: Carotenoid metabolism

A

Carotenoids are absorbed intact. Cleaved within the mucosal cell or can be transported unmetabolized into portal blood circulation. Can also be cleaved in the liver. Cleaved by 15,15’-dioxygenase.

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21
Q

Vit A: Hepatic uptake and storage

A
  1. Retinyl esters are taken up by parenchymal cells of liver. 2. Esters are hydrolized in parenchymal cells and then stored in stellate cells as retinyl esters. 3. LRAT involved in forming ester. 4. Within cell, retinold binds CRBPI (different from protein in intestine).
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22
Q

Vit A: Stellate Cells

A

Vitamin A is stored here. RARE* for something to be stored here.

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23
Q

Vit A: Hepatic release

A

Retinol attaches to retinol-binding protein (RBP) in the liver, forming Holo-RBP. Holo-RBP is released into blood where it binds to transthyretin and thyroxin to form a trimolecular complex.

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24
Q

Vit A: Plasma transport

A

Apo-RBP binds to Holo-RBP. This binds to TTR to form a trimolecular complex.

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25
Q

Vit A: Trimolecular complex

A

reduces glomerular filtration, and thus renal catabolism

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26
Q

Vit A: Cellular retinol uptake

A

-TTR dissociates from complex holo-RBP binds to RBP receptor. – Complex is endocytosed— cytosolic release of retinol and apo-RBP

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27
Q

Vit A: Functions

A

Vision, Cellular differentiation & gene expression, growth, immune system, bone development and reproduction.

28
Q

Vit A: Vision

A

Vitamin A, as 11-cis-retinal, serves at the photosensitive chromophoric group of rhodopsin found in rod cells of the retina. Bound to the protein through the lysine residue.

29
Q

Vit A: Light and Rhodopsin

A

Rhodopsin detects small amount of light important for night vision.

30
Q

Vit A: Transformation of rhodopsin by light

A

Converts it from cis –> trans aka the visual cycle

31
Q

Vit A: Visual cycle

A

Purpose is to regenerate 11-cis-retinal. Steps 5 & 6*** CRALBP-11-Cis-retinal –> IRB-11-cis retinal –> 11-cris retinal

32
Q

Vit A: Vision continued.

A

All-trans-retinal must be converted ack to 11-cis-retinal to regenerate rhodopsin. Storage retinyl esters can be hydrolyzed, isomerized, oxidized to 11-cis-reitnal and shuttled to rod cell. – If storage is deficient, cannot regenerate sufficient 11-cis-retinal. Failure to regenerate 11-cis-retinal results in night blindless* Retinyl esters are stored as back up.

33
Q

Vit A: Cellular differentiation

A

Process whereby an immature cell is transformed into a specific type of mature cell.– Vitamin A is required for differentiation of specific cells.

34
Q

Vit A: Cellular differentiation examples.

A

Keratinocytes –> epidermal cells w/ retinoic acid…

Bone marrow can differentiate into lymphocytes, macrophages etc.

35
Q

Vit A: Cellular differentiation without retinoic acid

A

Squamos epithelial keratinizing cells –> replace mucous-secreting cells in many body tissues, results in keratinization of skin (dry, rough, and scaly)

36
Q

Vit A: Cell differentiation and infection

A

Important for bronchial passages which have a barrier function– mucous secreting cells & ciliated cells… In vitamin A deficiency, barrier is compromised and increases the risk of infection.

37
Q

Vit A: Gene expression

A

In cytosol, retinol is oxidized to all-trans-retinoic acid and 9-cis-retinoic acid which binds to CRABP (cellular retinoic acid binding protein)

38
Q

Vit A: CRABP

A

Cellular retinoic acid binding protein. Serves as a chaperone. Takes it to a specific place (nucleus). Then it binds to retinoic receptors RAR or RXR then form a dimer.

39
Q

Vit A: CRBP

A

serves in storage and transport. Not in the nucleus.

40
Q

Vit A: Gene expression main points

A

CRABP-bound all-trans-retinoic acid and 9-cis-retinoic acid translocate into nuclus and bind to specific receptors— RAR (all-trans-retinoic acid) & RXR (9-cis-retinoic acid). Vitamin-bound RAR and RXR bind to DNA at specific sites called retinoic acid response elements (RARE), located in promoter regions of specific genes. Binding results in increased transcription of specific genes**

41
Q

Vit A: Gene expression continued

A

Retinoids act as nuclear hormones involved in “signaling” pathways (bound to RAR/RXR) – Retinoids act as transcription factors regulating either the activation or repression of mRNA formation in nucleu

42
Q

Vit A: Vitamin A-DNA complexes

A

Proposed to affect large variety of cellular processes. –Cell differentiation and apoptosis (cell death) —-normal part of tissue growth and development.

43
Q

Vit A: Gene expression proposed mechanisms

A

effects of vitamin A on cellular differentiation, cell death, etc needed for normal growth and development.

44
Q

Vit A: Gene expression regulation

A

regulates genes that code for: proteins including enzymes & transcription factors required for cell differentiation and growth.

45
Q

Vit A: Growth

A

Deficiency impairs growth, which can be stimulated with retinol or retinoic acid. Retinoic acid stimulates growth by increasing expression of growth receptors on cell surface. Supplementation increases growth receptors on cell surface.

46
Q

Vit A: Maintenance of normal eye tissue

A

Retinoic acid maintains normal differentiation of cells– conjuctival membranes…. Prevents xerophthalmia. - drying of protective eye membrane. upregulated expression of mMRNA by retinoic acid for mucin proteins of the conjuctiva. ***Most important role of Vitamin A.

47
Q

Vit A: Stages of eye degredation

A

Xerosis –> keratomalacia (softening of cornea, ultimate involvement of iris/lens, secondary infections)…. dry eyes –> bitot’s spots –> corneal ulcerations –> keratomalacia

48
Q

Vit A: Blindness

A

250k/ yr, mainly in the developing world.

49
Q

Vit A: Immunity

A

Through cell differentiation & hematopoiesis and blood and lymphoid organ cell populations.

50
Q

Vit A: Immunity continued

A

Ability to respond to pathogens, antigens.. .Increases and decreases in number and function of: B cells, T cells, natural killer cells, antigen-presenting cells and macrophages.

51
Q

Vit A: Antibody

A

Involved in antibody responses to T cell-dependent antigens.

52
Q

Vit A: Lymphocyte/ Mucosal surfaces

A

Increasing lymphocytre proliferation responses to antigens…. Maintaining the integrity/ function of mucosal surfaces– upregulated expression of mRNA by retinoic acid for mucin proteins of respiratory tract.

53
Q

Vit A: Dermatology

A

Epithelial tissues sensitive to deficiency as well as excess vitamin A.

54
Q

Vit A: Synthetic Retinoids

A

Isotretinoin (accutane). Treatment of acne– Normalizes epidermis cell differentiation & reduces synthesis of sebum. 13-cis-retinoic acid. Hormonal form of vitamin A. Need a prescription

55
Q

Vit A: Accutane: Teratogenicity

A

Excessive intake in 1st trimester of pregnancy increases congenital defects. Malformation: craniofacial with low set, small or absent ears. Malformed facial bones. Defects in cardiac, thymus, CNS

56
Q

Vit A: World wide deficiency

A

20-40 million vit A def. children worldwide. – low fat/plant based diets. protein-calorie malnutrition. Need fat to absorb fat soluble vitamins

57
Q

Vit A: Deficiency

A

Blindness & Infection

58
Q

Vit A: Morbidity and mortality

A

Mortality in developing countries reduced by preventing vitamin A deficiency. Administered every 6 months reduced mortality in pre-school children, infants and pregnant women.

59
Q

Vit A: Subclinical deficiency

A

increased risk of respiratory and diarrheal infections. Decreased growth rates. Slow bone development. Decreased survival from serious illness.

60
Q

Vit A: Recommendations

A

WHO/ UNICEF recommends- children diagnosed with measles be given Vit A– incorporation of vitamin A supplements with immunization program…. American academy of pediatrics– treat “high risk” children with measles with Vitamin A.

61
Q

Vit A: Status indicator

A

Liver biopsy. Plasma retinol: poor indicator of low status unless severe* deficiency. Relative dose response (RDR) test: magnitude of increase in RBP following supplementation. Conjuctival impression cytology– field test (cheap, common, coffee filter with hole, stick on conjuctiva, cells attach and look at a microscope).

62
Q

Vit A: Cytology

A

cheap, common, coffee filter with hole, stick on conjuctiva, cells attach and look at a microscope

63
Q

Vit A: Units in food and supplements

A

Retinol Activity Equivalents (RAE). 1 RAE= 1 microgram retinol, 12 micrograms B-carotene, 24 micrograms alpha carotene or other provitamin A carotenoids.

64
Q

Vit A: RDA

A

700 females. 900 males.

65
Q

Vit A: Toxicity

A

Nausea and vomiting, headache, dizziness, blurred vision, lack of muscular coordination, abnormal liver function, pain in bone and joins… usually due to inappropriate use of retinoid supplements. Has occurred form excess conumption of liver.

66
Q

Vit A: B-carotene toxicity

A

Considered to be non-toxic. May cause skin discoloration. Controlled intervention studies provide evidence of increased risk for cancer in high-risk individuals (smokers)– 20-30mg/d for 4-6 years. May be due to pro-oxidant effects of B carotene.

Metabolism Exam 2 (3 decks)

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