Vit A

Question 1

Process of retinyl ester absorption

Answer 1

1. Hydrolysis (mediated by retinyl ester hydrolase)
2. Uptake (through the intestinal mucosa)
3. Esterification (reesterified via lecithin:retinol acyltransferase)
4. Chylo secretion (Chylomicron assembly of ester and secretion)

Question 2

Process of beta-carotene absorption

Answer 2

1. Uptake (through intestinal mucosa)
2. Esterification (first cleaved by carotenoid cleavage enzyme CMO and reduced by retinal reductase, cleaved portion of original molecule esterified by LRAT)
3. Chylo secretion (Chylomicron assembly and secretion)

Question 3

Liver in vit A metabolism

Answer 3

~75% of chylomicron retinyl taken up by liver; intermediate in vit A absorption; stores and supplies to the rest of the body

Question 4

Retinoid

Answer 4

Any naturally occurring or synthetic compund that resembles all-trans-retinol with or without vit A biological activity

Question 5

Vit A structure

Answer 5

Includes:
- Beta-ionone ring
- Isoprenoid chain (spacer)
- Polar end group

Question 6

Metabolic forms of retinoid

Answer 6

Non-active metabolites as metabolic intermediates or breakdown products for excretion - ex. retinal

Question 7

How are RAE, all-trans-retinol, B-carotene, and other provitamin A carotenoids equivalent

Answer 7

1 RAE = 1 all-trans = 12 mcg B-carotene = 24 mcg other provit A carotenoids

(1 IU = 0.3 RAE)

Question 8

Vit A makeup in out diets

Answer 8

2/3 = pre-formed vit A
1/3 = provit A carotenoids

Question 9

RDA vit A male vs female

Answer 9

Male (900 RAE) > Female (770 RAE)

Question 10

Vit A pregnancy and lactation

Answer 10

Increased during pregnancy for fetal growth and accumulation (770 RAE). Increased vit A secretion into breast milk (1300 RAE)

Question 11

Primary storage site of vit A

Answer 11

Liver retinyl esters

Question 12

Ideal assessment of vit A status

Answer 12

Liver biopsy because circulating retinol levels do not represent liver stores. Circulating vit A can be normal while liver stores are depleted.

Question 13

Tracer studies on vit A levels

Answer 13

Using a labelled retinoid tracer can estimate the body’s reserve of vit A. H:D is ratio of hydrogen to deuterium in plasma retinol used as part of the eqn to estmate total liver reserves.

Question 14

Circulating form of vit A

Answer 14

Retinol bound to retinol binding protein

Question 15

Functional metabolite of retinol for vision

Answer 15

11-cis-retinal (chromophore for vision)

Question 16

Functional metabolite of vit A for transcription

Answer 16

All-trans-retinoic acid is a transcription factor ligand

Question 17

Metabolism of all-trans-retinoic acid

Answer 17

Question 18

Phototransduction

Answer 18

11-cis-retinal undergoes photo-isomerization into all-trans-retinal when struck by light, leading to activation of G-protein, transduction. Phosphodiesterase activate, hydrolyzing cGMP. Leads to closure of Na+ channel, firing a signal to the brain.

Question 19

Nuclear receptors for retinoic acid

Answer 19

3 retinoic acid receptors RARs (alpha, beta, gamma) bind to consensus sequences in the promoter regions of target genes (retinoic acid response elements).

3 retinoid X receptors RXRs (alpha, beta, gamma).

Both function as dimers.

Question 20

Causes of vit A deficiency

Answer 20

• Malnutrition - developing world
• Fad diets - developed world
• Clinical conditions affecting lipid absorption - developed world

Question 21

Keratinization

Answer 21

Scarring of the cornea as a result of severe vit A deficiency (called xerophthalmia). Linked to retinoic acid role in maintaining epithelial integrity.

Question 22

Stages of xerophtalmia

Answer 22

1. Night blindness
2. Conjunctival xerosis
3. Bitot’s spots
4. Corneal xerosis (can be blinding)
5. Corneal ulcer (blinding)

Question 23

Vitamin A deficiency and immunity

Answer 23

Increased mortality with vit A deficiency assoc with impaired immunity.
1) decreased barrier function of epithelia (first line of defense) - susceptibility to UTI and resp infections
2) Impaired immune response - increased severity and duration of disease

Question 24

Most clinically significant diseases related to vit A deficiency

Answer 24

• Pneumonia
• Malaria
• Measles
• Diarrheal diseases

Question 25

Short and long-term interventions for VAD

Answer 25

Short-term:
- supplementation in conjunction with immunization programs

Long-term:
- Promotion of vit A rich food (limited by regional availability, seasonality, and expense)
- Fortification of staple foods (enrich with beta-carotene) like golden rice and orange maize

Question 26

3 categories of vit A toxicity and describe

Answer 26

1. Acute toxicity: consumption of single high dose of vit A (>200 000 IU) leading to increased intracranial pressure, causing headache, nausea and vomiting, loss of conciousness, coordination, possibly death…
2. Chronic toxicity: long-term consumption of high amounts of vit A (25 000 IU/day) assoc with dietary supplements, causes intracranial hypertension, hair loss, bone pain, liver damage, irritability
3. Teratogenicity: Excess vit A in pregnancy (>10 000 IU/day) resulting from supplement use or prescription drugs; increase rate of miscarriage and abnormalities