Micronutrients Flashcards
Iodine
THINK THYROID:
- typically found in ionic form (iodide) and ~70 to 80% is found in thyroid gland (free or bound to AAs)
- iodine from our diet is rapidly converted into iodide form and absorbed (mainly in stomach)
- once in our blood free iodide can permeate all our tissues (but mainly accumulates in thyroid gland)
- Iodide requires NIS to get into thyroid gland (ATPase maintains favourable gradient by pumping out sodium)
- once inside it is used to make thyroid hormones (T3 and 4) required by all of our tissues
- the liver converts T4 to T3 and it travels in our blood bound to specific carrier proteins
- T3 binds to receptors and interacts with response elements in promotor regions of DNA
- finally activating gene expression
How does Iodine make thyroid hormones?
- iodine is taken up by NIS
- iodine oxidizes in colloid cell to form free radical
- thyroid gland produces Tyr-rich thyroglobulin protein
- free radical attacks Tyr residues forming crosslinks
- thyroid cell proteases hydrolyze thyroglobulin and now you have thyroxine and triiodothyronine
Vitamin A
THINK (RETINOL) NIGHT BLINDNESS
- fat soluble vitamin absorbed by passive diffusion
- two forms: beta-carotene (from plants) and retinyl esters
- both forms go to liver in chylomicron remnant: beta-carotene stored in adipose and retinyl ester stored in liver
- esterase removes fatty acid so you are left with retinol (active form)
- Retinol binds RBP and gets released into blood and made available to cells
Beta-carotene
Inactive vitamin A provitamin
- retinol is bound in plant fibres so not easily absorbed
- 15, 15’ carotenoid mono-oxygenase enzyme liberates 2 backbones to retinyl esters
Retinol
Active form of vitamin A
- alcohol (so not very stable)
- junction point that can be converted to retinal (aldehyde) or retinoid acid
Retinal
Aldehyde form involved in vision
- retinol bound to RBP drops off retinol at pigment epithelial cells in eyes
- rapidly converted to all-trans retinal by dehydrogenase enzyme
- then isomerase enzyme converts it to 11-cis retinal
- 11-cis retinal combined with opsin in eye forms rhodopsin molecule
- when rhodopsin is hit with light the complex breaks apart
- 11-cis retinal is released from opsin and converted back to all-trans
- this signals low-light pathway
- isomerase has to convert all-trans retinal back to 11-cis form for cycle to continue
Retinoid acid
Form of vitamin A involved in gene expression
- retinol bound to RBP drops retinol off to cells
- converted to retinoid acid
- retinoid acid goes to nucleus and binds/activates receptors
- allowing specific regulation of gene expression
- specifically signals stem cells to differentiate (in epithelial tissues)
Vitamin D
THINK (Ca) SUN - bones
- acts as “true” hormone meaning it is made in kidney but acts on other tissues and works with other hormones (PTH and calcitonin)
- plant sources (contain ergosterol - provitamin D2) can be converted to vitamin D2 but not very active
- animal sources (contain 7-dehydrocholesterol which is provitamin D3) and can be converted to D3 by sunlight
- we ourselves can make vitamin D from sunlight and 7-dehydrocholesterol form in skin
How does sunlight produce vitamin D?
- pigment in our skin known as 7-dehydrocholesterol absorbs UV rays
- rapidly converted to vitamin D3 form
- binds to vitamin D binding protein (DBP) and travels through blood to liver
- in the liver 25-hydroxylase adds OH group to C25 forming 25-OH D
- again this travels through blood bound to DBP to kidney
- parathyroid gland can sense low levels of calcium and secretes PTH which promotes uptake of 2-OH 2/DBP complex in kidney
- this activates 1-hydroxylase which converts 2-OH D to calcitriol (active form)
Calcitriol signalling
Once vitamin D is activated it is sent out into the body and activates vitamin D receptors (genomic or non)
Genomic:
- receptors are ligand activated
- when calcitriol binds (VDR/NHR) they become active transcription factors and can go create proteins
- (vitamin K dependent)
Non genomic:
- calcitriol interacts with cell surface membrane receptors
- triggers signalling pathway cascade
- (Vitamin K independent)
Vitamin K
THINK CLOT (gamma-carboxylation)
- in our diet we get vitamin K from leafy greens (phylloquinone form - saturated side chain)
- most is produced by our own colonic bacteria though (menaquinone - unsaturated side chain)
- stored in cell membranes in lungs, kidneys, adrenal glands, bones, etc…
- vitamin K from diet >active hydroquinone> inactive epoxide
- vitamin K allows for gamma-carboxylation by acting as cofactor for conversion of glutamic acid residues to gamma-carboxyglutamic acid
- important function in blood clotting
Calcium
- represents about 40% of body’s mineral mass
- no very efficient absorption
- transported in body bound to albumin (40%), complexed with sulphate/phosphate (10%) or in free ionized form (50%)
- in bone (99%) minerals make up hydroxyapatite (crystal structure)
- intra and extra cellular function (1%) includes blood clotting, skeletal muscle contraction, nerve potential and intracellular signalling pathways
- uptake is encouraged by calcitriol (vitamin D)
- UL decreases in elderly population to prevent risk for hypercalcemia
- UL high in children
Calbindin
Class of calcium binding proteins
- produced thanks to calcitriol
- decreases with age
Phosphorus
- second most abundant mineral in body
- predominantly found in hydroxyapatite
- central role in metabolism
- key in protein phosphorylation (i.e. post translational modifications)
Fluoride
- present in trace amounts (not essential)
- major function is related to mineralization of bones and teeth