vitamin A and E: A

Question 1

What are the forms of vitamin A?

Answer 1

vitamin A are preformed vitamin A (retinoids)

Question 2

what is the structure of retinoids?

Answer 2

structurally similar containing a beta-ionone ring and a polyunsaturated side chain with an:
alcohol=retinol
aldehyde=retinal
carboxylic group=retinoic acid
ester=retinyl ester

Question 3

What are carotenoids?

Answer 3

provitamin A, precursor of vitamin A

Question 4

what are some facts of carotenoids?

Answer 4

of 600 carotenoids: 50 have vitamin A activity
-exist as expanded carbon chain with conjugated double bonds usually but not always with a beta-ionone ring at one/both ends of the chain

Question 5

What are some sources of vitamin A?

Answer 5

preformed vitamin A or retinoids

• foods of animal origin: liverm dairy, eggs, fish oils, tuna, sardines, herring
• main form in food is retinyl palmitate
• some foods may be fortified (e.g. skim milk/partially skimmed milk)

Question 6

What are some sources of carotenoids?

Answer 6

provitamin A

• brightly colored yellow, orange, and red vegetables
• beta-carotene: most abundant and contains greatest provitamin A activity
• other carotenoids: lycopene (tomatoes), lutein, beta-carotene, zeaxanthin

Question 7

What is RAE?

Answer 7

Retinol Activity Equivalent

Question 8

What are the conversion factors of vitamin A?

Answer 8

1 IU vitamin
= 0.3 microgram retinol (animal products)
= 3.6 microgram beta-carotene = 7.2 microgram of other provitamin A carotenoids

Question 9

What are the conversion factors of vitamin A?

Answer 9

1 RAE
= 1 microgram retinol
= 12 microgram beta-carotene
=24 microgram alpha-carotene or beta-cryptoxanthin

12x amount of beta-carotene or 24x amount of alpha-c or b-cryptoxanthin is needed to get the same effects as 1 microgram of retinol

Question 10

Vitamin A content of foods?

Answer 10

need a bit of heat and oil to release bioavilable beta-carotene to absorb and function
ex. carrots (cooked): may absorb 60% (raw 5%)

Question 11

Digestion of vitamin A?

Answer 11

vitamin A requires digestion before absorption

heating plant foods will weaken some complexes but enzymatic digestion still required

Question 12

Absorption of vitamin A?

Answer 12

70-90% vitamin A absorbed from a meal assuming it contains some fat

Carotenoid absorption <5% for uncooked veg.
60% with pure oil
(beta-carotene: ~20-50%)

-absorption in the duodenum and jejunum

Question 13

Digestion and absorption process of vitamin A

Answer 13

in the lumen of GI tract:
protein-bound carotenoids and retinyl esters–pepsin and other proteases–> release of aa and carotenoid and retinyl esters
–hydrolases, esterases, lipases–> free carotenoids and free retinol
–>incorporate into micelle–>cross brush border membrane (absorbed into enterocytes through passive diffusion)
no carrier proteins invovled

Question 14

Beta-carotene digestion and absorption

if not converted in enterocytes, can be converted in other cells

Answer 14

1. beta-carotene is converted into 2 retinal molecules
2. cellular retinol-binding protein (CRBP) II binds to both retinol and retinal in the intestinal cell
3. retinal (attached to CRBPII) reduced to retinol by retinal/retinaldehyde reductase to form CRBPII-retinol
4. Lecithin retinol acyl transferase (LRAT) esterifies fatty acid (palmitic acid) onto the CRBPII-bound retinol to from CRBPII-retinyl-palmitate
5. retinyl esters are incorporated along w/ phospholipids, TAG, cholesterol esters, carotenoids, and apoporteins to from chylomicron
6. chylomicrons leave the intestinal cell and enter the lymph system and ultimately the blood
7. retinoic acid can directly enter the blood–where it attaches to albumin for transport to the liver

Question 15

Cleavage of carotene to retinal

Answer 15

about 50% of carotene
–>vitamin A (impaired if iron-deficient)

• non-central cleavage via beta-carotene 9’10’ dioxygenase
• 15,15’-monooxygenase (iron dependent)

Question 16

Transport and metabolism of vitamin A

Answer 16

chylomicrons deliver retinyl esters, some unesterified retinol, and carotenoids to extrahepatic tissues (70-75%) –>liver

some carotenoids are taken up by scavenger receptor class B type 1 by peripheral tissues (e.g. eye) for local production of retinoids

Question 17

Vitamin A metabolism in the liver

Answer 17

1. retinyl esters are taken up into the lvier cells and the retinol and FAs are released by retinyl ester hydrolase
2. free retinol can be esterified via ARAT or it can bind to CRBP and be esterified by LRAT to form retinyl esters
3. retinyl esters are stored in stellate cells until needed
4. CRBP-retinol can be (1) converted into retinoic acid (2) attached to retinol-binding protein for release into the blood (3) can be conjugated with glucuronic acid to from retimul beta-glucuronide for excretion in the bile
5. retinoic acid binds to cellular retinoic acid-binding proteins (CRABP)
   –>function in nucleus (gene expression)
   or
   –>conjugated with glucuronic aicd and excreted in bile
   or
   –>converted into 4-OH retinoic acid –>4-oxoretinoic acid

Question 18

Vitamin A metabolism in the liver

Answer 18

6. 4-oxoretinoic acid may function in cells like retinoic acid
   or conjugated to glucuronic acid for excretion into bile
7. retinol attaches to retinol binding protein in the liver
   - ->complex holo-RBP
   - ->released into blood where it binds to transthyretin and thyroxine to form a trimolecular complex

Question 19

How will malnutrition impact vitamin A metabolism?

Answer 19

not enough protein–>body cannot form retinol binding protein
–>cannot get vitamin A out of liver to send out to other tissues

Question 20

Transport of vitamin A

Answer 20

-retinol that is esterified may be stored in the liver: stellate cells & parenchymal cells

• transported in blood via 2 proteins in a complex (involved in cellular uptake)
• retinol-binding protein (RBP, prealbumin)
• transthyretin (TTR, thyroxine binding globulin) transport out of hepatic cell–>other tissues

Question 21

Transport of carotenoids

Answer 21

transported as part of lipoproteins

• taken up by cells as part of lipoproteins and scavenger receptor class B type 1
• Carotenoids stored in liver and adipose

Question 22

Functions of vitamin A

Answer 22

1. vision: rhodopsin
   epithelial cells w/ mucous: GI tract, eyes, barrier against bacteria

2.gene expression: homodimers, heterodimers

3. cellular differentiation: keratinocytes (immature skin cells) to mature epidermal cells
   cell type-dependent: can inhibit/promote
4. growth and reproduction: mech. unclear
5. Bone metabolism: osteoblast/clast
   excessive vit A: excess osteoclast activity, reduced osteoblast acitivty
6. immune system
   roles in fighting against viral, parasitic, and bacterial infection?

Question 23

vitamin A: vision

Answer 23

Rhodopsin made up of dopsin
–>attach to optin cis-retinal to have function

light hits retina–>conformation change from cis-retinal to trans-retinal

because we only have cis-retinal and opsin to form–> change conformation–>no more rhodopsin
–>reconversion required
trans-retinal converted back to cis-retinal–>cis-retinal reattaches to opsin to reform rhodopsin

Question 24

Vitamin A: gene expression

Answer 24

2 forms of vitamin A:

all-trans retinoic acid and 9-cis retinoic acid regulate gene expression

Question 25

How is vitamin A involve in gene expression

Answer 25

1. all-trans or 9-cis retinoic acid moves into the nucleus of the cell bound to binding proteins 2. all-trans retinoic acid binds to retinoic acid receptors (RAR) and 9-cis retinoic acid binds to retinoid X receptors (RXR) 3. binding of the vitamin to receptors on the DNA enhances the transcription of selected genes

Question 26

Roles of Carotenoids

Answer 26

antioxidants: possess ability to react w/ and quench free radical rxns in lipid membranes/compartments and possibly in solution - series of 9/more conjugated double bonds-->soluble in lipids Quenching: process by which electronically excited molecules or atoms such as singlet molecular oxygen (from lipid peroxidation ex.) are inactivated -->will not become radicals itself-->dissipate as heat

Question 27

What are some fucntions of carotenoids?

Answer 27

1. cell proliferation, growth, and differentiation: carotenoids and cancer: inhibit cell proliferation, induce differentiation in vitro inhibit neoplastic transformation - 2. Carotenoids and eye health: age-related macular degeneration, cataracts -study results mixed -research does not support supplementation at this time

Question 28

Vitamin A's interaction with other nutrients

Answer 28

- excess vitamin A interferes with vitamin K absorption - High beta-carotene intake may decrease plasma vit E - Protein and zinc influence vitamin A status and transport - Iron metabolism interrelated w/ both carotenoids and vitamin A: (1) required for conversion of beta-carotene to vitamin A (e.g. 15, 15' mono-oxygenase) (2) vitamin A deficiency may be associated with iron-deficiency anemia (iron-dependent enzyme to cleave into 2 molecules of retinal)

Question 29

Metabolism and Excretion of vitamin A

Answer 29

- excreted in urine and feces (amount vary with intake) - most excreted in urine (60%): water-soluble metabolites -dose depend on intake -small amount from lungs -carotenoids metabolized to variety of compounds (water-soluble) and excreted into bile (can be reabsorbed from bile in small intestine if incorporated into micelle) -Polar vitamin A metabolites returned to liver through enterohepatic circulation and recycled partially conserving vitamin A stores

Question 30

What are some ways to assess vitamin A status?

Answer 30

eye examination (assessment of night blindness): assess level rhodopsin and rate of regeneration relative dose response (RDR) test or modified RDR test (MRDR) -someone takes dose of retinal ester, measure changes in plasma level

Question 31

What are some ways to assess vitamin A status?

Answer 31

Conjunctival impression cytology plasma retinol concentrations (depend on adequacy of energy, protein and zinc) if enough protein, zinc, just vitamin A level deficient cannot look at plasma level: will only show evidence when liver store depleted

Question 32

What are some facts and diseases associated with vitamin A deficiency?

Answer 32

associated with increased mortality and eventual blindness night blindness, Bitot's spots Xerophthalmia, keratinization Measles depresses vitamin A status (thought via absorption, requirement and increased urinary vitamin A excretion) Vit A supplements recommended by WHO for treatment of measles in populations where deficiencies are likely

Question 33

What is the upper limite of vitamin A

Answer 33

UL = 3000 ug RAE (10,000 IU)

Question 34

What is the toxicity of vitamin A?

Answer 34

Hypervitaminosis A: - teratogenic (e.g. >4500 ug RAE during pregnancy) - damages liver - increased bone fractures - hair loss beta-carotene causes hypercarotenemia but does not damage liver etc. (no UL set for carotenoids): orange discoloration of skin -supplements of either are not advised, consume in diet (e.g. 2 1/2 cups fruits and vegetables per day

Question 35

Are Canadian adults meeting the requirement for vitamin A?

Answer 35

no adults reaching UL for diet alone | supplement did not change that

Question 36

What is the prevalence of low blood levels of vitamin A and C in American Children 6-11 years old?

Answer 36

Prevalence of low blood level of vit.A in children (1%) not quite deficient but can have mild deficiency ~2% of the population 6 years of age and older at risk of excess vit.A (100 ug/day)

Question 37

What is the prevalence of low blood levels of vitamin A and E in Americans? 1999-2005

Answer 37

Prevalence of low serum vitamin A < 1% Prevalence of high vitamin A 1 - 2% (not lots of ppl have excess vit A) Prevalence of low vitamin E <2%