UNIT 9: MICRONUTRIENTS I: Iodide, Vitamin A Flashcards
What is a SHR and what is it’s function?
Steroid hormone receptor
- binds hormone ligands –> transcription factors (bound complex) regulate gene expression
What is the difference between the 2 types of SHR?
Type 1: cytosol
- bind steroids only
Types 2: nucleus
- bind steroids and non steroids
All ligands that bind to SHR are steroid hormones.
True/False
False
Type II bind both
(only vitD is steroid hormone from cholesterol)
Iodide, Vitamin A, Vitamin D bind ____
SHR Type II
I2 is ___
I- is ___
Iodine (elemental) I2
IodiDe = anion I-
Which form is found in diet iodine/iodide.
IodiDe (I-)
absorbed well in GIT
What is a good source of iodide?
Seafood - higher iodide intakes in costal populations
- fortification of iodide in salt
What is the main role of iodide in the body?
Synthesis of thyroid hormones
Iodide is converted to T3 and T4
What is the bioactive form of thyroid? What does the other form act as?
T3 is bioactive form
made from T4 (thyroxin)
T4:T3 ratio is 20:1 since T4 is a reserve pool
The thyroid bioactive form binds to the SHRII domain called ___
Thyroid Hormone Receptor (THR)
T3 binds THR
Which enzyme converts T4 –> T3
5’deiodinase enzyme
What mineral is required in order for T4 –> T3?
Selenium required for 5’deiodinase enzyme
Deficiency and dysregulate metabolic rate
What happens if metabolism rate is dysregulated?
Dysregulation by selenium deficiency
- Hypothalamus senses this change in metabolic rate
- Thyroid stimulating hormone (TSH) secreted to blood stream –> increase metabolic rate
- TSH arrives to thyroid cell and up regulates iodide transport and increase in T3 and T4 production
- Increase T3 and T4 synthesis
Iodide deficiency leads to:
- chronic secretion of TSH fro hypothalamus
- enlargement of thyroid
- increase T3 and T4 production (but depends on deficiency)
A radical is formed in the thyroid via:
iodide + hydrogen peroxide
= reactive IODIDE species
What does the hydrogen peroxide radical in the thyroid attack?
thyroglobulin - tyrosine rich protein in thyroid gland
- iodine added to tyrosine ring
- iodized thyroglobulin cross linked together
T3 is ____ and can cross biological mebranes
lipophillic
T3 binds ___ in the ____
T3 binds THR (thyroid hormone receptor) in the nucleus
complex
- incr. transcription
Free THR in the nucleus leads to
decrease in transcription
T3 signalling occurs with good nutritional status and signals ___
growth hormone synthesis
Iodide deficiency is called ____
goiters
Low dietary and blood iodide, thyroid cannot produce T3 and T4. What happens?
- Pituitary increases blood TSH secretion
- excessive stimulation
- hyperplasia
- hypertrophy
= goiters
Iodine deficiency during pregnancy can lead to ___
Cretinism/ cognitive impairment
- deficiency in maternal iodide
- stunts mental and physical growth
- inability to walk or talk
Vitamin A is a _____ vitamin.
fat-soluble vitamin
These are the 5 forms of vitamin A. Distinguish them.
- Retinol
- Retinal
- Retinyl palmitate
- Retinoic acid
- Carotenoids
- alcohol form
- aldehyde form
- ester form (retinol + palmityl CoA)
- carboxylic acid form (binds SHRII)
- i.e. beta carotene (greatest vitamin A activity)
Vitamin A is obtained from:
Plants: carotenoids
Animals: retinyl esters
(metabolized to retinol, retinal, retinol palmitate, retinoid acid)
What is the main source of vitamin A from plants?
beta carotene (carotenoids) also metabolized to (1-->4)
The digestion of vitamin A compounds like retinyl ester and beta carotenes is from a _____
fat droplet from the stomach
- goes through lipid digestion
(triglycerides, phospholipids + vitamin A compounds)
Retinyl ester is broken down by what enzyme?
Pancreatic retinyl esterase
retinyl ester –> palmitate + free retinol
Beta carotene from the fat droplets goes to ___
passive diffusion via the brush border
does not require digestion
What are the two metabolic fates of beta-carotene?
- incorporated into chylomicron WITHOUT modification
- clipped to retinal, reduced to retinol
- via enzyme 15,15’dioxygenase
retinol –> retinyl palmitate –> incorporated chylomicron
(both incorporated into chylomicron: one as beta carotene, one as retinyl palmitate)
15,15’dioxygenase catalyzes retinal –> retinol
- what regulates this enzyme?
vitamin A status
- high levels inhibit this
Chylomicrons, once in circulation, is taken up by what regulatory organ?
The liver
- as a chylmomicron remnant
- releases beta carotene and retinyl palmitate in liver (none is released in tissues)
What happens to beta carotene once it arrives in the liver?
incorporated into VLDL
- stored in adipose tissues (uncontrolled)
What happens to retinyl palmitate once it arrives in the liver?
retinyl palmitate –> retinol
retinol + RBP (retinol binding protein)
= retinol-RBP binding complex
retinol-RBP released to blood
In the blood, what form of vitamin A is present? (after the liver)
retinol-RBP
Once it reaches the target tissue destination, what happens retinol-RBP?
retinol-RBP is converted to it’s active forms at the tissues
- 11-cis retinal (retina)
- Retinoic acid
Retinol-RBP acts as a ____ to vitamin A
The inactive precursor acts as a homeostatic setpoints.
*active hormones are NOT setpoints
Which form of vitamin A regulates night vision?
11-cis retinal
What are other biological roles of vitamin A?
- cell differentiation
- growth
- synthesis of glycoproteins
- reproduction
- bone metabolism
- immune function
What form of vitamin A regulates its biological roles?
retinoic acid (regulated by binding to type II SHR)
What is rhodopsin?
= 11-cis retinal + opsin
- Retinol-RBP (Blood) –> retinol (rod cells) –> all-trans retinal –>11-cis retinal
+ opsin
What happens when light hits the cis bond in rhodopsin?
- molecule bounces back to all-trans-retinal form to release opsin
- transmit nerve impulse (dim purple light)
Retinoic acid binds to:
Where?
- retinoic acid receptors (RAR)
- retinoid X receptors (RXR)
in the nucleus - lipid soluble
What happens to the retinoic acid/receptor complex?
dimerizes and binds to promotor region of DNA –> transcription of mRNA –> ribosome assembly –> proteins
Proteins regulated by vitamin A including ___growth hormones; ____ collagenase
- increase growth hormones
- decreased collagenase
Vitamin A is really important to ______ differentiation
All epithelial cell differentiation
(lungs, trachea, cornea, sclera, GIT, esophagus, mammary, skin)
Retinoic acid signals differentiation
What happens in terms of epithelial differentiation if there is a deficiency in vitamin A?
Deficiency –> impaired gene control and secretes hard keratin instead of mucous
Deficiency in ____ leads to night blindness.
11 - cis retinal
Impaired epithelial differentiation is a deficiency in _____
Retinoic Acid binding to type II SHR
- keratinization
- impaired growth of bones/teeth
- impaired fertility (sperm formation)
- birth defects
Vitamin A deficiency causes _____ blindness.
Reversible/preventable
keritinization of cornea - severe blindness
What are Bitot’s spots?
reversible buildup of keratin outside the cornea (impaired mucosal cell differentiation)
What is hypervitaminosis A?
Vitamin A toxicity
What does vitamin A toxicity cause?
liver damage
- excess retinyl palmitate in the stellate cells of the liver
- stellate cells proliferate
- scar tissue
- liver failure
Therapeutic index of vitamin A is ______
narrow
TI = 3
Are carotenoids toxic?
no
- they do not stress excess retinol in the liver (goes straight to VLDL to adipose)
