Vitamin A

Question 1

Vitamin A is a generic descriptor for…

Answer 1

• retinoid and carotenoid compounds that exhibit biological activity of retinol

Question 2

Essential structure features of naturally occuring vitamin A (retinol, retinal, retinoic acid) (6)

Answer 2

• Substituted þ-ionone nucleus
  
  • CANNOT monkey around with this
• Polar functional group at C-15
• Esterification usually at C-15
  
  • Storage form (retinyl palmitate), ingested from animal sources
• Side chain at C-6 composed of isoprenoid units
• Conjugated DB from C-5.
  
  • Rentinol: lambda max=325nm
  • Retinoic acid: lambda max=350nm
• Cis isomers sterically hindered (exceptions)
  
  • 11-cis retinal undergo cis-trans isomeration in visual cycle
  • 9-cis and 13-cis RA treatments for acne/cancer

Question 3

Carotenoids

Answer 3

• Carotenoids
  
  • Carotenes
    
    • Beta (2), alpha (1), lycopene (0)
  • Xanthophylls
    
    • Cryptoxanthin (1), lutein (0)
• Polyisoprenoid plant pigments; pro-vitamin A
• Beta carotene most active b/c two retinal after cleace 15-15 C bond with BCMO (monooxygenase)
  
  • inefficient when vitamin A stores high

Question 4

Vitamin A Metabolism

Answer 4

• Retinyl esters→Retinol with REH (retinyl ester hydrolase)
• Retinol→Retinal (aldehyde) with NAD Alcohol dehydrogenase (ADH)
  
  • Retinal→Retinol with Aldo-Keto Reductase (AKR)
  • Involve hydride transfer
• Retinal→Retinoic Acid with Aldehyde Dehydrogenases
  
  • Need cysteine and NADPH
• Retinoc Acid→Other shit
  
  • CYP26A1 and B1
  • 4 hydroxylation on beta-ionone ring

Question 5

Vitamin A dietary sources (3)

Answer 5

• Plants (carrots, sweet potatoe, red pepper) provide carrotenoids
• Animal (liver) retinol esters
• Fish oils, effs, fortified dairy products also important vitmain A source

Question 6

Vitmain A Transport and Storage

Answer 6

• Specific transport proteins
  
  • CRBP, CRABP, RBP for retinoic acid, retinal and retinol
  • Stored in liver as ester

Question 7

Vitamin A Functions: General categories

Answer 7

• Vision
• Growth and Development
• Immunity

Question 8

Vitamin A in Vision

Answer 8

• In rhodopsin cycle
• Two isomerizations:
  
  • Light: 11-cis retinal to all trans retinal
  • Retinoid isomerhydrolase: all trans retinyl palmitate to 11-cis retinol
• Oxidize 11-cis retinol to 11-cis retinal
• 11-cis retinal bind to opsin via Schiff base (imine formation)

Question 9

Vitamin A in Growth and Development

Answer 9

• Regulates synthesis of macromolecules
  
  • via RAR and RXR activated transcription
• Keratinization of cornea→xerophthalmia
• Production of transferrin→anemia
• Bone: low/high intake→weak bones
• Skin→fissures allow infection

Question 10

Vitamin A in Immunity

Answer 10

• Alter mucosal surface
• Impaired antibody responses
• Changes in lymphocyte subpopulations
• Altered T and B cell function
• Measles killer

Question 11

Vitamin A Deficiency

Answer 11

• plama retinol <0.7 microM
• Night blind, dry skin
• Associated with infectious disease, which also lower vitA

Question 12

Vitamin A: Daily Requirement

Answer 12

• DV=5000 IU
• UL=10,000 IU (~3000 µg)
• 1µg=3.3 IU
• Lowest TI; only two fold
• RAE (retinol activity equivalent)
  
  • 1 µg all trans retinol
  • 2 µg all trans B carotene in oil
  • 12 µg food all trans B carotene
  • 24 µg all other mixed diet carotenoids
• Supplements; acetate ester
• RDA: male=900 µg RAE (2900 IU); females=700µg (2300 IU); breat feeding=1300µg (4000 IU)

Question 13

Vitamin A: Uses (General)

Answer 13

• Antioxidant
• Cancer
• Skin

Question 14

Vitamin A Use: Antioxidant

Answer 14

• Lycopene, prevent prostate cancer
• Luteine, prevent macular degeneration
• Need mg doses (~6-30mg)
  
  • Multivitamins not provide enough

Question 15

Vitamin A Use: Cancer

Answer 15

• Retinoic Acid promote cell differentiation and inhibits cell proliferation
• low carotene intakes increase lung cancer
  
  • Supplement beta carotene increased cancer risk
• Tretinoin (all trans retinoic acid) for promyelocytic luekemia
  
  • myeloid cells not differentiate

Question 16

Vitamin A Uses: Skin

Answer 16

• Topical acne: retinoic acid
• Isotretinoin (13 cis retinoic acid) Accutane
• Psoriasis: etretinate (Tegison)⇔acitretine (Soriatane)
• Orall=strong teratogens

Question 17

First Generation Vitamin A Drugs

Answer 17

• All trans retinoic acid
  
  • tretinoin
  • PML
• 13-cis retinoic acid
  
  • Isotretinoin
  • Accutane
• 9-cis retinoic acid
  
  • Alitretinoin
  • Trates Kaposi scarcoma (AIDS)

Question 18

Second Generation Vitamin A Drugs

Answer 18

• Etretinate (Tegison)
  
  • 4 mo half life
• Acitretin (Soriatane)
• Acitretin→Etretinate with alcohol
• Pregnant in 2 years, stay away

Question 19

Third Generation Vitamin A Drugs

Answer 19

• Bexarotene
• Taxarotene
  
  • T-cell lymphoma
  • Category X: jury out if okay cream in pregnancy
• RXR ligand/agonists
• Skin conditions

Question 20

Vitamin A Toxicity

Answer 20

• Increased birth defects if above 10,000 IU…others say 30,000 IU
  
  • Liver consumption in pregnancy
• Hypervitaminosis A: vomit, hypercalcemia, brittle bone, fatigue….
  
  • Chronic ingestion: 25,000-50,000
  • Polar bear liver: 20,000-30,000 IU/g
• Hypercarotenosis: too many carrots, yellow, okay
• Increased bone fracture over 10,000 IU

Question 21

Vitamin A Counseling/Consumer Advice (4)

Answer 21

• Avoid doses over 5000 IU/d of retinol
• Avoid eating liver frequently, or cod liver oil
• Avoid B-carotene as single dietmary supplement (smoker)
• Veggies are best! BCMO has feedback regulation for carotenoid to retinal conversion