1
Q
Iodine
A
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
2
Q
How does Iodine make thyroid hormones?
A
- 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
3
Q
Vitamin A
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
4
Q
Beta-carotene
A
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
5
Q
Retinol
A
Active form of vitamin A
- alcohol (so not very stable)
- junction point that can be converted to retinal (aldehyde) or retinoid acid
6
Q
Retinal
A
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
7
Q
Retinoid acid
A
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)
8
Q
Vitamin D
A
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
9
Q
How does sunlight produce vitamin D?
A
- 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)
10
Q
Calcitriol signalling
A
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)
11
Q
Vitamin K
A
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
12
Q
Calcium
A
- 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
13
Q
Calbindin
A
Class of calcium binding proteins
- produced thanks to calcitriol
- decreases with age
14
Q
Phosphorus
A
- second most abundant mineral in body
- predominantly found in hydroxyapatite
- central role in metabolism
- key in protein phosphorylation (i.e. post translational modifications)
15
Q
Fluoride
A
- present in trace amounts (not essential)
- major function is related to mineralization of bones and teeth
16
Q
Vitamin E
A
THINK BREAKING BAD
- umbrella term for 8 vitamins (4 tocopherols and tocotrienols)
- really only care about alpha-tocopherol (1/8 that has activity in body - most methylated)
- absorption takes place in jejunum (requires bile salts to get into solution)
- packaged into chylomicrons once inside body
- CR arrive at liver and drop off vitamin E
- liver makes tocopherol transfer protein (TPP) which is required to get alpha-tocopherol packaged into VLDL
- in cells located primarily in membranes to provide antioxidant support
17
Q
ROS lines of defense
A
When electrons leak out and interact with surrounding oxygen they form a moderately reactive super anion radical - super oxide dismutase (SOD) enzyme converts radical to hydrogen peroxide then enters GSH
- GSH (glutathione) peroxidase (selenoprotein)
- converts hydrogen peroxide into water OR hydrogen peroxide can accept another electron from something else and form a highly reactive hydroxyl radical
- hydroxyl radical steals electron from whatever it can (usually PUFA in membrane)
- now you have a PUFA free radical which interacts with oxygen to form a PUFA peroxy radical
- PUFA peroxy needs an electron to form PUFA hydroperoxide but without something to give that electron keeps taking from PUFA next to it and you are stuck in a cycle…enter vitamin E - Vitamin E is a very stable molecule so it donates an electron and can survive without it but we also still need to deal with PUFA hydroperoxide so final line of dense comes in
- FA peroxidase - converts PUFA hydroperoxide into PUFA alcohol
18
Q
Selenium
A
- associated with plant proteins (plants incorporate selenium instead of sulfur into AAs)
- 2 very important selenoproteins that provide super antioxidant support (GSH peroxidase and FA peroxidase)
- both use glutathione as substrate (acts on reducing agent - composed of glutamate, cysteine and glycine and structure is crucial)
19
Q
Vitamin C
A
THINK ASCORBIC ACID (hydroxylation reactions)
- exists in both D and L isomers but L is the biologically active form in humans
- many mammals can produce it from glucose except for humans, primates, fruit bats, guinea pigs and some birds (we lack gulonolactone oxidase enzyme)
- transported via sodium dependent vitamin C 1 and 2 transporters in small intestine
- found in circulation in free form (primarily)
- tissue concentrations are greater than plasma
- involved in a number of biological processes acting primarily as reducing agent (2 electron donor)
- signs of deficiency related to problems producing hydroxyproline (collagen)
20
Q
Vitamin C role in hydroxylation reactions
A
- donates an electron to reduce ferric iron to ferrous iron to regenerate prolyl hydroxylase enzyme
- prolyl hydroxyls coordinates hydroxylation
- especially important in collagen synthesis
NUTR 3210
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