Summary Micronutrients 1: Vitamin A, vitamin D and iodide. Vitamin K, calium,
phosphorus and fluoride (associated)
-Minerals are inorganic and vitamins are organic.
-When vitamins aren’t present in diet or aren’t absorbed or utilized properly, a deficiency disease
-Vitamins can’t be made, you need to get them from the diet.
Type II SHR (steroid hormone receptors)
• Present in the nucleus of the cell
• Bind to both steroid hormones and non-steroid hormone ligands
• Ligand/receptor complex forms a transcription factor that can up- or down-regulate the
expression of genes. Most of the time it will up-regulate.
• Ones of interest to us: thyroid hormone (iodine), retinoic acid (vitamin A), calcitriol (vitamin
D, related to steroid hormone. The other ones are non-steroid ligands)
• We call it iodide because in
most food sources and in our
bodies iodine is found in its ionic
• It is very poorly distributed
globally so there are serious
problems with deficiencies in
developing countries (13% of the
•Iodine is the only micronutrient
that is taken up by only one organ
(thyroid gland) if it isn’t already
saturated with iodine.
•Iodide enters the thyroid gland via active transport and gets converted to T3 and T4 thyroid
hormones (1:20) (see next point for how) T4 is the precursor to T3 (active form) so the body
makes lots of precursors. • T3 & T4 is made in thyroid gland from post translational modification of thyroglobulin,
involving an attack by a reactive Iodide radical.
•T4 gets converted to T3 in the liver via 5’-deiodinase which is a selenoprotein.
• Mostly T4 in circulation, with T3 (active) being formed in the liver
• Levels of T3 are monitored by hypothalamus. When T3 levels are low, the hypothalamus sends
a signal via TRH (thyrotropin releasing hormone) to the anterior pituitary which sends a signal
via TSH (thyroid stimulating hormone) to the thyroid gland to make more thyroid hormones.
•If iodide is not present in the thyroid gland, this cycle will become very active and TSH builds
up, cells get bigger and you have major problems.
• Proteins are expressed in
response to T3 include growth
hormone and mineral ATPases,
which regulate metabolism
• Iodide deficiency causes
hyperplasia and hypertrophy of the
thyroid gland (goiter) and mental
Vitamin A : Family of molecules. Fat soluble
•Includes beta carotene, other carotene (plants) and Retinyl esters (animals) which get converted
to retinol, retinyl palmitate, all-trans retinal, 11-cis retinal and retinoic acid (active forms)
• Main plant provitamin (precursor to vitamin A) is beta carotene, which is the orange pigment
in plants (also other carotenes, but minor importance, although they can similarly be converted to
retinal). It acts as an antioxidant in the plant, but not so much in animals.
• Animal forms are retinyl esters (mainly retinyl palmitate; storage form in animals). A lot is
found in liver and egg yolks and milk.
• Beta carotene can be clipped to 2 molecules of retinal by 15,15’dioxygenase and then oxidized
to retinol BUT it can also be stored as beta carotene in adipose
• Activity of 15,15’dioxygenase is down regulated when levels of retinol are high. •Retinyl esters (from meat) and
beta carotene (from plants) are
consumed and found in fat droplets
in the stomach
•Beta carotene enters directly into
the intestinal mucosal cell (doesn’t
get digested). Then it can either
undergo cleavage to retinol (see
above) or nothing happens to it and
it gets incorporated into the
•Retinyl esters get digested to
retinol via pancreatic retinyl
esterase and then retinol enters the
IMC. Retinol is a detergent so it
has to get converted to retinyl
palmitate to be stored or
transported in chylomicrons.
•As the chylomicron goes around
the body to drop things off, beta
carotene and retinyl palmitate stay
on until the remnant gets to the
•When they arrive at the liver, the beta carotene gets incorporated into VLDL and gets
distributed to the adipose tissues (mainly). If you get too much of this, you’ll turn orange.
• Retinyl palmitate can be stored in the liver in stellate cells or re-converted to retinol via retinyl
esterase. The retinol combines with retinol binding-protein (RBP) for transport to target tissue.
This complex is not active, but it is a homeostatic set point (precursor to vitamin A).
•Retinol-RBP regulates 15, 15’ dioxygenase and retinyl esterase.
• Two functions of vitamin A: (1) night blindness (active form 11-cis-retinal) and (2) gene
expression (retinoic acid)
• In night vision: retinol RBP in bloodretinol in tissue all-trans retinal 11-cis-retinal +
opsin rhodopsin Isomerase The light in a dim room strikes retina (where rhodopsin is) and rhodopsin snaps apart, reforming
opsin and all Trans retinal. Bright light causes all rhodopsin to be destroyed to it takes a while to
adjust to dark rooms because you need to reform rhodopsin.
• In gene expression, retinol all-trans retinal retinoic acid + retinoic acid receptor/retinoid
X receptor (dimerizes) increased transcription of growth hormone, decreased transcription of
collagenase, amongst others.
•Because there are 2 types of receptors, each with
several family members, a lot of different
transcription factors will be able to be formed, so a
lot of genes will be able to be regulated. On top of
that, there is homodimerization and
heterodimerization, i.e. each ligand-receptor
complex will form a dimer with a different of same
ligand-receptor complex. Basically, a lot of proteins
are regulated by vitamin A
Vitamin A deficiency
•Night blindness is the first sign of vitamin D deficiency. Reversible.
•Vitamin A is needed for proper epithelial cell differentiation, and impaired epithelial cell
differentiation can cause blindness and life-threatening infections as consequences. If stem cells
don’t differentiate, they go to default and make keratin which builds up on these undifferentiated
cells and cells can’t do their job to protect body from infections.
•Impaired growth and fertility.
• Vitamin A deficiency is the leading cause of preventable blindness, and major cause of death in
developing countries, particularly among young people.
• RDA is measured in Retinol Activity Equivalents (accounts for intake of carotenoids) • UL is only concerned with intake of retinol (beta-carotene is safe)
• Narrow therapeutic index (TI)
Vitamin A toxic