Vitamin A & K Flashcards
Vitamin A
Types
Animals contain colorless Vit A βΎ retinol (active)
Plants contain colored carotenes βΎ ex. π½-carotene (inactive)
Animals can convert carotenes into active Vit A.
Vitamin A
Structure
βVit Aβ refers to any chemical form of retinol (tech. only alcohol form).
π½-carotene and other carotenoids are provitamins.
Cleaved in the middle by dioxygenase βΎ 2x retinal (aldehyde form)
Carotenoid Pigment
Sources
Dark green and yellow fruits and vegetables:
- spinach
- carrots
- sweet potato
- squash
- cantaloupe
Compared to raw carrots, cooking carrots breaks down the cell wall and improves bioavailability of carotenoids.
Retinol Sources
Liver, kidney, fortified milk, and eggs.
- Most dietary retinol in the form of retinyl ester with LCFAs
- Esters hydrolyzed in intestinal mucosa releasing retinol
- Re-esterified in intestine and secreted as part of chylomicrons
- Taken up by liver and retinol released as needed
- Transported in plasma complexed to retinol binding protein (RBP)
- Complex taken up by cells.
Vitamin A
Dietary Quantification
Retinol content show in mcg.
Carotene does not yield 1 πg of retinol per πg of carotene.
Represented using two terms:
-
RE (retinol equivalents) - older term
- based on prior notion that 6 πg of π½-carotene β 1 πg of retinol
-
RAE (retinol activity equivalents)
- now know that 12 πg of π½-carotene β 1 πg of retinol
- 24 πg of other carotenoids β 1 πg of retinol
- RAE values calculated from known πg of carotene in a product
Vitamin A
Visual Cycle
Visual cycle involves 4 forms if Vit A and 4 different opsins.
- 11-cis-retinal bound to protein via Schiffβs base link βΎ 11-cis-retinilidene in rod outer segment.
- Light strikes β isomerization βΎ all-trans-retinal
- All-trans-retinal released from opsin
- Reduction βΎ all-trans-retinol
- Travels to retinal pigment epithelium
- All-trans-retinol isomerized to 11-cis-retinol
- Oxidized to 11-cis-retinal
- Can again form Schiffβs base with opsin in rod outer segment.
Vision and Opsins
Retinal-opsin complexes with different absorption spectra.
Forms basis for color vision.
-
Cones
- 3 different opsins
- responds to blue, green, and red
-
Rods
- only contain rhodopsin
- absorption spectrum in the middle of the 3 cone spectra
- very sensitive to light βΎ night vision
- more severely affected by Vit A deficiency βΎ night blindness
Vitamin A
Metabolic Roles
Hormone-like role in differentiation of epithelial cells βΎ mucus-secreting cells, esp. in eyes.
Mediated by retinoic acid receptor (RAR) β binding of retinoic acid-RAR complex to regulatory elements β β gene expression.
Suppresses keratin formation.
- Vit A deficiency causes
-
protein deposit forms instead of moist mucus membrane
- cornea destroyed β corneal ulceration
- vision loss becomes irreversible
-
atrophic β to mucosal surface
- Loss of globlet cells
- Replacement of nl epithelium w/ inappropriately keratinized stratified squamous
-
protein deposit forms instead of moist mucus membrane
Role in maintaining immune competence β barrier to infection.
Unclear role in hematopoiesis, bone growth, and reproduction.
Vitamin A
Clinical Uses
Retinoic acid uses:
- Acne treatment
- Some cancers β promyelocytic leukemia
Vit A
Deficiency
Uncommon in US but major cause of blindness and death in developing countries.
- Signs of deficiency:
-
Follicular hyperkeratosis
- βgoose bumpsβ not due to cold
- due to excess keratin
-
Xerophtalmia
- spectrum of ocular diseases
- changes include:
- conjunctival and corneal drying (xerosis)
- corneal ulceration and melting (keratomalacia)
- night blindness (nyctalopia)
- retinopathy
- Bitotβs spots (build-up of superficial keratin debris in conjunctiva)
- Can affect any age group
- most common in 1-6 y/o
- most severe blinding complications in 6 m/o to 3 y/o
-
Follicular hyperkeratosis
-
Increased risk of death from infection
- measles in children from under-developed countries
Combating Vit A Deficiency
- Supplementation
- Food fortification
- Education on good sources
- Genetically-modified foods
- βgolden-riceβ β transgenic rice that produces lots of π½-carotene
Vit A
Toxicity
Lipid-soluble β can be stored in very large amounts.
RI 700-900 RAE.
-
Acute-toxicity
- rarely seen
- excess free retinol (not bound to RBP) lyses membranes
- acute illness ~ 300 mg in adults
- death at very high doses
-
Chronic overdose
- more serious problem
- caused by excessive dietary supplementation with preformed Vit A
- π½-carotene not toxic
- 7.5 - 7.9 mg/day TUL
- see liver and bone effects
- symptoms:
- hair and skin changes
- joint pain
- headaches
- fatigue
- Retinoic acid / synthetic retinoids highly teratogenic
- 1st month of pregnancy most sensitive
Vitamin K
Structure
Two classes (vitamers):
-
Phylloquinone (K1)
- only compound in plants
- also found in animals
-
Menaquinone (K2, also called MK)
- found only in animals
- variable chain contains repeating isoprenoid groups
- activity varies with repeats
- named for # of groups
- MK-7 contains 7 groups
- MK-7 and MK-9 predominant ones in gut
-
Menadione
- can be metabolized to MK-4
- once used as supplement but caused hemolytic anemia d/t G-6-P dehydrogenase inhibition
- low doses still used in cattle and pet foods
Vit K
Sources
Major dietary source is vegetables esp. dark green ones.
β collards, spinach, and kale
Animal products provide lower amounts.
β meats and diary fats (butter, cheese) but not milk
Intestinal flora synthesizes small amounts of K2 and converts K1 β K2.
Vit K
Absorption
Phylloquinone is the predominant dietary form.
- Absorbed in intestines via lymphatic system.
- Decreased with biliary insufficiency.
- In the plasma, Vit K1 and K2 incorporated into chylomicrons.
- Taken up by liver as CM remnants.
- Distributed to tissues as VLDL/LDL.
Vit K
Biological Functions
Coenzyme in πΎ-carboxylation of proteins by πΎ-glutamyl carboxylase.
Some proteins must be πΎ-carboxylated to be active:
β blood coagulation factors II, VII, IX, and X
β protein C and protein S (regulates blood coag)
β osteocalcin (bone protein binding hydroxyapatite)
β matrix Gla protein (MGP) (found in organic matrix of bone)
After πΎ-carboxylation, Vit K in epoxide form.
Must be regenerated back to quinone form by vitamin K epoxide reductase (VKOR).
Inhibitors of VKOR reduces blood clotting.
Ex. Coumadin
