vitamin A Flashcards
what is the definition of vit A
Fat soluble
Includes all naturally occurring compounds with the biological activity of retinol and pro-vitamin A carotenoids:
what are the Preformed vitamin A retinoids (3 vitamers)
Retinol
Retinaldehyde
Retinoic acid
what are Pro-vitamin A carotenoids
Of >500 known natural carotenoids, only ~50 converted to vit A.
Cleaved to yield retinaldehyde, and hence retinol & retinoic acid.
Not all carotenoids can be converted to vitamin A
Carotenoids natural are associated with plant material and algae
name some Chemical structures that have genuine vit A biological activity:
retinol
retinaldehyde
all-trans-retinoic acid
11-cis-retinol
9-cis-retinoic acid
explain carotenoids
Photosynthetic Pigments widely found in nature – photosynthetic tissue.
Yellow, orange or red.
Yeast, bacteria, fungi, vegetables, fruit.
Animals cannot synthesise carotenoids but can deposit them in body tissues with or without alteration of the basic structure.
They participate in photosynthesis
Pink colour in flamingos is due to feeding on plankton in water with carotenoids which is a pink colour , Same situation for salmon
Most carotenoids in our diet are from plant material
name some Major pro-vitamin A carotenes structures
alpha carotene
beta carotene
gamma carotene
beta-cryptoxanthine (3hydroxy-beta-carotene)
what are the Major pro-vitamin A carotenes able to metabolise
Able to be metabolised into retinol or retinoic acid
what does it mean by - carotenoids without vit A activity
ones don’t confer vit A activity
what are some Carotenoids without vit A activity and explain them
Lycopene – is associated with tomatoes
Not essential nutrient, but
prominent phytochemical
Cooking tomatoes increases bioavailability of lycopene
Lutein
Luteus – yellow colour
Functions in the eye (reduce risk of macular degeneration and cataracts in eye)
Used as Food additive (E161b) – extracted from marigold petals
Zeathanthin
Xanthos – yellow colour
Found in Maize corn and leaves of green plants
what are some vit A retinol sources
Foods of animal origin and a small number of bacteria, mainly in the form of retinyl palmitate in animal tissues.
Liver
Fatty fish
Egg yolk – egg yolks yellow so indicates this
Milk
Butter
Enriched margarine
what are some carotenoids food sources
associated with (red, orange, yellow) plant material in diet
Carrots, peppers, tomatoes
Brocolli, kale, spinach, brussels sprouts, green beans
Peaches, apricots, mangoes, pink grapefruit, melon
explain absorption of retinol and of carotenoids
Retinol: ~70-90% is normally absorbed.
Carotenoids: ~5-60%, depending on carotenoid and cooking.
Absorption of carotenoids and retinol impaired if diet provides <10% E from fat. So bioavailability reduced
explain the bioavailability of beta carotene
The most biologically active carotenoid.
Pure β-carotene yields 50% the vitamin A activity of retinol:
conversion factor 2:1 pure β-carotene : retinol
Lower bioavailability from plant sources:
conversion factor 6:1 β-carotene : retinol
describe the bioavailability in terms of the conversion factor of other carotenoids excluding beta carotene
Conversion factor is 12:1
total vit A in foods is expressed as what
as μg retinol equivalents (REQ)
1 μg REQ = 1 μg preformed retinol
6 μg β-carotene
12 μg other carotenes with vit A activity
REQ = ∑preformed vit A + (β-carotene/ 6)+ (other pro-vit A carotenoids/ 12)
Vit A content of foods used is to be expressed in what units
in standardised international units: 1 IU = 0.3 μg retinol or 0.6 μg β-carotene
explain the formation of retinol from carotenes
Beta carotene absorbed and oxygen added and enzyme carotene dioxygenase, which forms 2 retinal aldehydes
That’s then converted to retinol by enzyme retinol dehydrogenase or retinoic acid by aldehyde oxidase
explain absorption transport and storage of vit A
Bile will act as emulsifier breaking liquid up inro smaller units allowing enzymes to digest the fat
Bile forms a micelle which the fats are incorporated into and is where the digestion happens
Everything lipid soluble is digested into micelle structure to absorb it.
Cant absorb anything lipid soluble without bile secretion, which you need enough fat in the diet to get this bile secretion so is why we need aft in diet for vit A absorption.
We form lipoproteins which he protein emulsifies the fat in this structure which salifies it.
Chylomicron enters lymphatic circulation
When in blood circulation it travels through tissues which remove some of the trigylcerol for their own purposes
whys liver good vit A source
There are significant stores of vit A in liver so is why it’s a good source of vit A
explain the stages involved in absorption transport and storage of vit A
Absorbed from small intestine dissolved in lipid
Retinyl esters formed in the intestinal mucosa enter lymphatic circulation in chylomicrons with dietary lipid & carotenoids
then either:
Tissues can take up retinol esters from chylomicrons
or
Most remains in chylomicron remnants that are
taken up by liver where the esters are hydrolysed
after Most remains in chylomicron remnants that are taken up by liver where the esters are hydrolysed
theyre either:
Retinol Stored as esters in stellate cells in liver
or
Vitamin secreted from liver bound to retinol-binding protein (RBP)
RBP delivers the vitamin to target tissues
functions of vit A
Vision - forms light sensitive complex rhodopsin(as this is produces from retinol) in retina – night vision
Gene expression & cell differentiation – such as of blood cells, and during embryonic development
Morphogenesis – (making our morphology) & embryogenesis- (making embryo)
Growth
Integrity of the immune system
beta-carotene is an antioxidant. (Retinol isn’t a antioxidant though)
- High intakes associated with low incidence of Cardio Vascular Disease & some cancers, but not as supplements!
explain vit A and vision
Vit A - essential to vision at low light intensity.
In the retinal pigment epithelium of the eye, all-trans-retinol is isomerised to 11-cis-retinol and oxidised to 11-cis-retinal.
11-cis-retinal binds to the amino group of lysine on the light sensitive protein opsin to produce rhodopsin.
Rhodopsin is a light absorbing complex in the rods.
Rhodopsin is used in low light intensities
Exposure to light activates 11-cis-retinal/rhodopsin complex.
This generates Electrical signals which are transmitted to the optic nerve, enabling the eye to adapt to low light intensity and darkness.
explain vit A importance in gene expression and cell differentiation
Control of cell differentiation & turnover.
All-trans-retinoic acid & 9-cis-retinoic acid are involved in regulation of growth, development & tissue differentiation, with different actions in different tissues.
Retinoic acid binds to nuclear receptors that bind to control regions of DNA, thereby regulating gene transcription.
There are two families of nuclear retinoid receptors:
RAR (retinoic acid receptors)
RXR (retinoid X receptors)
explain vit A in terms of Morphogenesis + embryogenesis
Biological effects of retinoic acid are mediated by changes in gene expression caused by the RARs & RXRs.
Change in expression of RARs influences neural tube closure.
Switch in expression from RAR-γ (gamma) (open neural tube) to RAR-β (closed neural tube) is essential for proper posterior neural tube closure. – its though that folate is important in signalling molecule in change between beta and gamma receptor
Exposure to excess retinoic acid may result in congenital neural tube defects. Due to it affecting the ‘switching’ process
Retinoic acid has been implicated in expression of many genes which determine sequential development of various parts of an organism.
So is why recommended pregnant females don’t eat liver or too much vit A
what country is largely deficient in vit A
majority of Africa
what are the WHO Stages of xerophthalmia
Night blindness -> Bitot’s spots -> keratomalacia
Xerophthalmia = full vit A deficiency
Keratomalacia interferes with all vision so become completely blind
what is night blindness
Impaired colour vision: loss of sensitivity to green light.
Impaired ability to adapt to dim light.
Inability to see at all in dim light (night blindness).
what are bitots spots
White marks on the eye
Its areas of the eye that are becoming keratinized
There are other pathological reasons why bitots spots may form
They have a foamy and cheesy state
what is keratomalacia
Where cornea is affected so all vision is lost
Enzyme dissolves the cornea
This process sis irreversible
how does vit A deficiency impair immune response
Mild deficiency → ↑ susceptibility to infectious diseases.
↓ RBP synthesis in liver in response to infection → ↓ circulating vit A conc and further impairment of immune responses.
how does vitamin A deficiency occur secondary to protein - energy malnutrition (PEM)
Theres Impaired RBP synthesis (delivers vitamin to target tissues) – so inadequate vit A delivery to tissues.
who is at risk of vit A deficiency
Those with diets low in animal fats & vegetables
Low protein diets
Fat malabsorption + low dietary fat
Children in developing countries from birth to 5y (peak 2-3y)
name and explain methods for prevention and treatment of vit A deficiency
- Supplementation
Deficiency rare in UK.
India – large doses of vit A in oil given every 4-6 months effective in children. Incidence of toxicity low.
Vit a supliments Often done at same time as immunization activities or deworming of children. Every twice a year - Nutrition education
30g fresh green leaves or some fruit could prevent deficiency.
Often fails due to insufficient emphasis on maintaining altering behaviour. - Fortification
Margarine + oil
Dried skimmed milk (vits A + D)
Sugar (Guatemala, mid 1970’s) - Golden rice
GM to contain β-carotene.
GR2 – super golden rice, more
beta carotene
Places where staple food was rice, vit A deficiency was common so GM rice so it has beta carotene this gave it a yellow colour
where do excessive high intake of vit A accumulate
liver
vit A toxicity occurs from more than how many mg/d of vit D in adults
> 7mg/d
what are some symptoms of vit A toxicity
Central nervous system: headache, nausea, ataxia & anorexia
Liver: hepatomegaly with histological changes in liver (liver enlarges), increased collagen formation (scarring)& hyperlipidaemia.
Bones: joint pains, thickening of long bones, hypercalcaemia &
calcification of soft tissues.
Skin: excessive dryness, scaling & cracking of skin (so vulrneable to infection) & alopecia
explain vit As Toxic effects in pregnancy
Retinol is teratogenic in first trimester, causing:
- Spontaneous abortion
- Birth defects
- Permanent learning disabilities
Advised against retinoid therapy, liver or supplements
explain carotene - animal sources of vit A, and its toxic affects
Not known to have any adverse effects except giving orange-yellow colour to skin (hypercarotenosis) – unusual but not unheard of
However intervention trials in 1990s found ↑ lung cancer mortality in supplemented group.
how can we use liver stores to asses vit A status
Most accurate – direct assessment of status.
Can’t be readily determined in living subjects.
how can we asses vit A status by Looking at Plasma (or serum) retinol – via blood sample
Insensitive indicator of status (levels maintained constant over wide range of intakes). Its not precise
< 10 μg/100ml (0.3 μmol/l) – clinical deficiency state
< 20 μg/100ml (0.7 μmol/l) - marginal deficiency
how can we asses vit A status by looking at breast milk conc
May be used to indicate status in lactating women.
vit A requirements are Based on intakes needed to maintain what and why
liver conc of 70μmol/kg
This is adequate to maintain normal plasma concs.
Individuals with this level of liver reserves can exist on vit A-free diet for months before developing signs of deficiency.
what are the RNIs for vit A during different stages of life
11-14y 600 (M) 600 (F)
15-50+y 700 (M) 600 (F)
Pregnancy - +100 (F)
Lactation - +350 (F)
