Vit A Flashcards
Process of retinyl ester absorption
- Hydrolysis (mediated by retinyl ester hydrolase)
- Uptake (through the intestinal mucosa)
- Esterification (reesterified via lecithin:retinol acyltransferase)
- Chylo secretion (Chylomicron assembly of ester and secretion)
Process of beta-carotene absorption
- Uptake (through intestinal mucosa)
- Esterification (first cleaved by carotenoid cleavage enzyme CMO and reduced by retinal reductase, cleaved portion of original molecule esterified by LRAT)
- Chylo secretion (Chylomicron assembly and secretion)
Liver in vit A metabolism
~75% of chylomicron retinyl taken up by liver; intermediate in vit A absorption; stores and supplies to the rest of the body
Retinoid
Any naturally occurring or synthetic compund that resembles all-trans-retinol with or without vit A biological activity
Vit A structure
Includes:
- Beta-ionone ring
- Isoprenoid chain (spacer)
- Polar end group
Metabolic forms of retinoid
Non-active metabolites as metabolic intermediates or breakdown products for excretion - ex. retinal
How are RAE, all-trans-retinol, B-carotene, and other provitamin A carotenoids equivalent
1 RAE = 1 all-trans = 12 mcg B-carotene = 24 mcg other provit A carotenoids
(1 IU = 0.3 RAE)
Vit A makeup in out diets
2/3 = pre-formed vit A
1/3 = provit A carotenoids
RDA vit A male vs female
Male (900 RAE) > Female (770 RAE)
Vit A pregnancy and lactation
Increased during pregnancy for fetal growth and accumulation (770 RAE). Increased vit A secretion into breast milk (1300 RAE)
Primary storage site of vit A
Liver retinyl esters
Ideal assessment of vit A status
Liver biopsy because circulating retinol levels do not represent liver stores. Circulating vit A can be normal while liver stores are depleted.
Tracer studies on vit A levels
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.
Circulating form of vit A
Retinol bound to retinol binding protein
Functional metabolite of retinol for vision
11-cis-retinal (chromophore for vision)
Functional metabolite of vit A for transcription
All-trans-retinoic acid is a transcription factor ligand
Metabolism of all-trans-retinoic acid
Phototransduction
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.
Nuclear receptors for retinoic acid
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.
Causes of vit A deficiency
- Malnutrition - developing world
- Fad diets - developed world
- Clinical conditions affecting lipid absorption - developed world
Keratinization
Scarring of the cornea as a result of severe vit A deficiency (called xerophthalmia). Linked to retinoic acid role in maintaining epithelial integrity.
Stages of xerophtalmia
- Night blindness
- Conjunctival xerosis
- Bitot’s spots
- Corneal xerosis (can be blinding)
- Corneal ulcer (blinding)
Vitamin A deficiency and immunity
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
Most clinically significant diseases related to vit A deficiency
- Pneumonia
- Malaria
- Measles
- Diarrheal diseases
Short and long-term interventions for VAD
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
3 categories of vit A toxicity and describe
- 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…
- 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
- Teratogenicity: Excess vit A in pregnancy (>10 000 IU/day) resulting from supplement use or prescription drugs; increase rate of miscarriage and abnormalities
