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© Endeavour College of Natural Health endeavour.edu.au 1
NMDF211
Nutritional Biochemistry
Micromineral Pharmacokinetics
Session 4
© Endeavour College of Natural Health endeavour.edu.au 2
Session Objectives
Understand the biochemical processes underpinning the
digestion, absorption, transportation and metabolism of:
Trace minerals
• Minerals the body requires
in very small amounts
– Copper
– Iron
– Manganese
– Zinc
• Clinical issues of micromineral metabolism
Ultratrace minerals
• Minerals the body requires
in even smaller amounts
– Chromium
– Iodine
– Molybdenum
– Selenium
– Boron
– Vanadium
© Endeavour College of Natural Health endeavour.edu.au 3
Introduction of Microminerals
❖ Unlike the macrominerals that largely serve as structural
components or involved in fluid balance the
microminerals are primary enzyme cofactors.
❖ The multivalency common with many of the micro metal
ions permits them to exchange electrons between
substrate and cofactor.
❖ In contrast nearly all metal ions in the macromineral
category are monovalent and are not capable of
donating or accepting electrons. (Encyclopaedia of Human Nutrition, 2013)
© Endeavour College of Natural Health endeavour.edu.au 4
Introduction of Microminerals
❖ Enzymes that have the metal ion bound firmly are
referred to as metalloenzymes.
❖ With few exceptions, metals in the micromineral class fit
into the picture as cofactors for metalloenzymes.
(Encyclopaedia of Human Nutrition, 2013)
© Endeavour College of Natural Health endeavour.edu.au 5
Introduction of Microminerals
❖ One exception is Selenium. Selenium has properties
similar to sulphur, therefore can replace sulphur in the
structure of amino acids that make up the enzyme's
structure.
❖ Thus, when functioning as a cofactor, selenium is
present as selenocysteine and selenomethionine and not
as elemental selenium coordinated to the protein
structure.
(Encyclopaedia of Human Nutrition, 2013)
© Endeavour College of Natural Health endeavour.edu.au 6
Trace minerals
© Endeavour College of Natural Health endeavour.edu.au 7
Copper sources and forms
Food Sources
Animal Plant
Organ meats e.g. liver Rice
Meat and poultry Fruit
Legumes
Dairy products Potatoes
Eggs Nuts and seeds
Seafood Forms
Oysters, crabmeat, cuprous (Cu+)
prawns, lobster cupric (Cu2+)
(Refer to table 13.6, pg. 510, Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 8
Copper Absorption
(Copyright, Cengage 2018, Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 9
Copper Absorption & Transport
❖ As Cu is bound to proteins in the foods, HCl and pepsin act
on them to release and reduce bound Cu in the stomach. Cu
is primarily absorbed in duodenum. 50-80% of ingested Cu is
absorbed.
❖ The reduction of Cu (Cu 2+ to Cu 1+) occurs by the action of
ferric/cupric reductase in the presence of acidic environment
and vitamin C.
❖ The absorption of Cu 1+ at brush border is conducted by
copper transporter 1 (Ctr1) and divalent mineral transporter 1
(DMT 1).
© Endeavour College of Natural Health endeavour.edu.au 10
Copper Absorption & Transport❖ In the intestinal cells, Cu is bound to amino acids (esp
histidine & cysteine), glutathione and
proteins/chaperones (as free Cu may harm the
intestinal cells).
❖ On entering the enterocyte, Cu may be stored with
metallothionein with zinc, or used functionally within
the enterocyte, or transported across basolateral layer.
❖ Across the basolateral layer, Cu is transported by
active transport by ATPase (ATP7A in extrahepatic
cells and ATP7B in the liver). Mutations in ATP7a and
ATP7b (liver) causes Menke’s and Wilson’s disease
respectively.(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 11
Copper Absorption & Transport❖ From the intestinal cells, Cu is transported to liver by albumin
and α 2 macroglobulin.
❖ Uptake into the liver is done by Ctr1, Ctr2 and DMT1.
Chaperones bind to Cu for intracellular transfer.
❖ In the liver, it is then used for formation of ceruloplasmin(6 Cu atoms-blue colour protein).
❖ Ceruloplasmin constitutes 60-70% of circulating Cu in the
blood. The liver is the main organ that stores Cu. On
percentage bases, skeleton and liver have the most stored
Cu.
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 12
Copper function❖ Cu acts as enzyme cofactor.
❖ Cu containing superoxide dismutase is one of the major
endogenous antioxidant and removes superoxide radical
from the body.
❖ Cu containing Ceruloplasmin and Hephaestin are critical
for iron utilization in the body.
❖ Cu containing cytochrome c oxidase participates in energy
production in the mitochondria.
❖ In tyrosine metabolism, Cu dependent enzymes are
indispensable.
(Gropper & Smith, 2018)
Fe 3+
Ceruloplasmin 2+
Fe 2+
Ceruloplasmin 1+
© Endeavour College of Natural Health endeavour.edu.au 13
Factors influencing Cu absorption
Cu agonists
1. Amino acids
especially histidine, methionine, cysteine, glutathione
2. Organic acids
e.g. citric, gluconic, lactic, acetic, and malic acids. Citrate in particular has been found to form a stable complex with copper to improve absorption.
3. Glutathione
within lumen of gastrointestinal tract and intracellularly
Cu antagonists
1. Zinc – induce copper deficiency
- amounts about 40 mg or more impair copper absorption and diminish copper storage
- intestinal metallothionein decreases copper availability due to binding.
2. Phytates - mainly found in plant foods esp. grains, inhibits copper absorption
3. Iron – large amounts may affect absorption
4. Molybdenum – Forms an insoluble complex with copper which inhibits absorption
5. Antacid ingestion – may decrease copper absorption and induce deficiency
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 14
Revision Questions❖ In foods, copper is bound to proteins. What is required
to hydrolyze copper to allow its absorption?
❖ Name the soluble intracellular protein which binds to
intracellular copper and delivers it to various locations
across the intestinal and liver cell.
❖ Name the main copper transporter in blood.
❖ Name three factors which decrease copper absorption.
❖ List two pathways that copper supports in the body.
© Endeavour College of Natural Health endeavour.edu.au 15
IronFood sources
Haem sources (about 50-60%):
• Organ meats
• Poultry
• Fish
Non-Haeme sources:
(usually bound to components of foods)
• Nuts Legumes
• Grains Tofu
• Dairy products Eggs
• Fruit Vegetables
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 16
Iron
Forms
1. Ferric – Fe3+
2. Ferrous – Fe2+
haeme
In Humans
65% is found in haemoglobin
10% myoglobin
1-5% is found as parts of enzymes
At physiological pH, iron exists in the oxidized, ferric (Fe3+) state.
To be absorbed, iron must be in the ferrous (Fe2+) state or bound
by a protein such as heme.
© Endeavour College of Natural Health endeavour.edu.au 18
(copyright@Cengage, Gropper & Smith, 2018)
Iron Digestion & Absorption
© Endeavour College of Natural Health endeavour.edu.au 19
Heme iron digestion & absorption
❖ Proteases help separate (hydrolyse) haem (with Fe2+)
from haemoglobin or myoglobin before absorption in
stomach and small intestines.
❖ Haem separated from globin goes freely through brush
border with the help of Haem carrier proteins.
❖ Once inside the intestinal cell, the Haem oxygenase
enzymes releases Fe2+
❖ Fe2+ is soluble even in alkaline environment for
absorption.(West and Oates, 2008, Ems & Huecker, 2019, Gropper and Smith, 2018, pg 482-483.)
Iron Digestion & Absorption
© Endeavour College of Natural Health endeavour.edu.au 20
Non heme iron digestion & absorption (Fe3+ )
❖ Non heme iron bound to food components is hydrolysed
with the help of proteases, HCl in the stomach and SI. It is
soluble and available for absorption only in the acidic
medium.
❖ Some Fe3+ may be reduced to Fe2+ by Vitamin C dependent
‘Reductase enzymes’ in the lumen. This Fe2+ is
transported by DMT1 at brush border.
❖ Most of the Fe 3+ remains insoluble in alkaline medium
and forms complex and is excreted as Fe(OH)3.
(West and Oates, 2008, Ems & Huecker, 2019, Gropper and Smith 2018, pg 482-483.)
Iron Digestion & Absorption
When proton-pump inhibiting drugs
such as omeprazole are used, iron
absorption is greatly reduced. Why?
© Endeavour College of Natural Health endeavour.edu.au 21
Iron uptake and storage
(Gropper & Smith, 2013)
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Intestinal use of Fe2+ (enterocytes)
❖ Free Fe2+ is not available for long as iron can cause free
radical production (Fenton reaction).
❖ Hence as soon as it enters the enterocytes, it is bound to
either amino acids (cysteine & histidine) or mobilferritin.
❖ Fe2+ may be used for enzyme functions, stored in ferritin,
or used by cells for their own use or to make heme.
Retinoic acid is required to liberate iron from ferritin via
erythropoietin.
❖ Whatever is left is transferred across the basolateral border
by Ferroportin. Here Fe2+ need to be converted to Fe3+ by
copper containing protein Hephaestin.
Iron Absorption & transport
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 23
❖ Ceruloplasmin in plasma can also convert Fe2+ to Fe 3+.
❖ Now Transferrin binds to Fe 3+ for circulation in the
blood and is transported to other tissues.
❖ The transmembrane protein ferroportin is the only efflux
route of cellular iron and is regulated almost exclusively
by hepcidin levels.
Iron Absorption & transport
If iron levels in the blood are high, hepcidin
binds ferroportin and prevent its efflux into the
blood and results in the degradation and
shunting of cellular iron into ferritin stores and
prevents its absorption into the blood. Why do you think body has such a mechanism?
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 24
Factors influencing iron absorption
Dietary inhibitors
1. Polyphenols – tea, coffee
(may absorption by up to
40%)
2. Oxalic acid – spinach, chard,
berries, chocolate, tea (may
reduce iron absorption up to
60%)
3. Phytates
4. EDTA (IV chelating agent)
5. Phosvitin – protein in egg
yolks
6. Nutrients – calcium, zinc,
manganese, nickel
Dietary enhancers
1. Acids – ascorbic acid, citric,
lactic and tartaric
2. Sugars
3. Meat, poultry, fish or their
digestion products
4. Mucin (endogenous
synthesised chelator – a small
protein made in both gastric
and intestinal cells)
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 25
• Haemoglobin and myoglobin-oxygen delivery
• Electron transport-ATP production
• Amino acid metabolism
• Niacin and carnitine synthesis
• Procollagen synthesis
• Thyroid hormone synthesis
• Destruction of bacteria, virus and microbes
• DNA synthesis
• Carbohydrate metabolism
❖ Toxicity: Unbound iron is toxic and act as a pro-oxidant.
Genetic disorder: hemochromatosis
(Gropper & Smith, 2018, pg 490-494)
Iron: Functions
© Endeavour College of Natural Health endeavour.edu.au 26
Revision Questions❖ List two forms of iron found in foods and how is their
absorption at brush border different?
❖ List three foods/nutrients which may inhibit iron
absorption?
❖ List three foods/nutrients which may enhance iron
absorption?
❖ Name two copper containing compounds that are essential
for iron transport?
❖ Iron is transported in the circulation bound to_________.
❖ Name the storage form of iron in the enterocyte and which
nutrient is needed to release iron from that form?
❖ List three nutrients that interact and affect iron metabolism.
© Endeavour College of Natural Health endeavour.edu.au 27
Sources and forms of Manganese
Animal Plant ‘Luxury’
Dairy Legumes Coffee, tea
Fruit Wine
Root veg Beer
Dried fruit
Nuts
Forms
1. Mn2+ (divalent)
2. Mn3+ (trivalent)
Manganese functions both as an
enzyme activator and as a
constituent of metalloenzymes.
Refer to pg 535 of Gropper &
Smith, 2018 and discuss three of its
main functions.
© Endeavour College of Natural Health endeavour.edu.au 28
Manganese Digestion & Absorption
❖ Manganese absorption (likely as Mn2+ ) is less than 5%
and absorption decreases as intake increases.
❖ Females may absorb greater amounts than males for
unclear reasons.
❖ At brush border, it is absorbed by DMT-1 and/or Zrt like
proteins (ZIP). At high does, it is absorbed by diffusion.
❖ At basolateral layer, mechanism of transport is not
known: Mn is either free or is bound to α 2 macroglobulin
and travels to the liver.
❖ Upon release from the liver, it may be free (an Mn 2+ ), or
bound to albumin and α macroglobulin, or oxidised by
ceruloplasmin and/or complexed with transferrin.
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 29
Manganese Digestion & Absorption
Free Mn2+
Or
-2 macroglobulin
After leaving the liver, Mn2+ may oxidise via
circulating ceruloplasmin to Mn3+
Complex with transferrin
Extra-hepatic tissues
Storage
In most cells especially in:
1. Bone
2. Liver
3. Pancreas
4. Kidney
Transferrin Mn3+
Free Mn2+ , or bound to
Albumin or
-2 macroglobulin
(Cell receptor mediated)
Mn2+
Mn3+
Mn3(PO4)2
Little information is available on Mn absorption.
Basically it occurs throughout SI, most likely by
saturable, low-capacity, high affinity active transport
such as DMT1
© Endeavour College of Natural Health endeavour.edu.au 30
o Absorption enhancers
• Ligands:
– Histidine
– Citrate
• Low intake of Mn increases
absorption
• Low intake of Fe increases
absorption
o Absorption inhibitors
• Manganese complexes in
GI with
– Oxalates
– Phytates
– Phosphorus
• Competitive divalent metals
– Fe, Cu
• High intake of Mn
decreases absorption
Factors Influencing Manganese
Absorption
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 31
Revision Questions
o Name two ways manganese is transported
through circulation?
o Iron competes for absorption with manganese.
Why may this be the case?
© Endeavour College of Natural Health endeavour.edu.au 32
Zinc
Found in all organs and tissues primarily intracellular.
Sources
Oysters Crab meat
Prawns Tuna
Meat Poultry
Pork Eggs
Milk Legumes
Grains Cereals
Vegetables Fruit
Forms
Can exist in several different states but is almost universally found as the divalent ion Zn2+
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 33
Zinc Digestion and Absorption
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 34
Factors affecting Zn absorption
Enhancers
1. Citric acid
2. Picolinic acid
3. Histidine, cysteine, and
possible other amino acids
such as lysine and glycine
4. Pancreatic secretions
(unidentified constituent)
5. Glutathione
6. Tripeptides
7. Low zinc status
Inhibitors
1. Phytates, Oxalates,
Polyphenols
2. Fibre
3. Folate
4. Nutrients – divalent cations
such as magnesium, iron,
calcium
5. Antacids, H2 receptor
blockers, PPI’s
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 35
Zinc Transport & Storage
Storage Transport in Blood
In all body organs/tissues
1. Liver
2. Kidney predominant
3. Muscle storage
4. Skin
5. Brain Storage in cells
6. Lung small Metallothionein:
7. Heart amounts contains cys residues that
can bind to Zn2+ but also to
Cu2+,Cd2+ and Hg2+
Bound to various proteins:
Albumin
α-2 macroglobulin
Transferrin
Low weight binding proteins
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 36
Zinc: Functions
• Cofactor for several
enzymes
• Growth - regulation of
transcription
• Cell replication
• Bone formation
• Skin integrity
• Cell-mediated immunity
• Generalized host defense
• Carbohydrate metabolism
© Endeavour College of Natural Health endeavour.edu.au 37
The Clinical Importance of Zinc
❖ Zinc deficiency during growth periods results in growth
failure.
❖ Epidermal, gastrointestinal, central nervous, immune,
skeletal, and reproductive systems are the organs most
affected clinically by zinc deficiency.
❖ Zinc is one of the most important trace elements in the
organism, with three major biological roles, the catalytic,
the structural, and the regulatory.
❖ Significant disorders of great public health interest are
associated with zinc deficiency.
© Endeavour College of Natural Health endeavour.edu.au 38
The Clinical Importance of Zinc
❖ It is essential for the structure and function of various
proteins and cellular components and plays an important
role in human physiology from its involvement in the
proper function of the immune system to its role in
cellular growth, cell proliferation, cell apoptosis, as well
as in the activity of numerous zinc-binding proteins.
❖ Zinc also plays a key pathophysiological role in major
neurological disorders, such as in Alzheimer’s disease,
cancer, aging, diabetes, depression, and Wilson’s
disease.
(Chasapis, 2012; Roohani, 2013)
© Endeavour College of Natural Health endeavour.edu.au 39
Revision Questions
❖ Name three substances which enhance zinc absorption?
❖ Name three substances which may inhibit zinc
absorption?
❖ What two transporters zinc uses for absorption across
brush border?
❖ Name a storage protein of zinc.
❖ What other substances might bind to zinc?
© Endeavour College of Natural Health endeavour.edu.au 40
Ultratrace minerals
© Endeavour College of Natural Health endeavour.edu.au 41
Sources of Chromium
Animal Plant ‘Luxury’
Beef, turkey breast Grains Beer
Organ meats Spices
Poultry (cinnamon,cloves, bay leaf) Wine
Mushrooms Tea
Brewer’s yeast
Molasses
Brown sugar
• Brewer’s yeast contains Glucose Tolerance Factor (GTF).
Potentiates action of insulin. Complexes with nicotinic acid and
AA to form Glucose Tolerance Factor (GTF).
• Refining foods decrease chromium content
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 42
Forms of Chromium
❖Chromium exists in a series of oxidation states
from Cr -2 to Cr 6+.
❖The most relevant with respect to nutrition are:
• Cr3+ (Trivalent chromium) is the most stable form and found to be
the most important to human function
• Cr6+ (Hexavalent chromium) is a skin irritant, carcinogenic,
respiratory and kidney toxin (US Department of Health & Human Services,
2012).
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 43
Chromium: Digestion & Absorption❖Cr3+ may be released from the food components in
acidic solution (in the stomach) and is then absorbed
in jejunum.
❖At brush border, it is understood to be absorbed via
passive diffusion or carrier-mediated transporter,
and/or endocytosis.
Transport
• Cr3+ binds with transferrin in blood.
• If no transferrin, then Albumin transports it.
• Globulins, possibly lipoproteins may also transport
chromium.
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 44
Chromium Digestion & AbsorptionIn acidic conditions (stomach HCL-)
Cr3+ is soluble
Binds to ligands
(Nitrogen, Oxygen and Sulphur)
Absorption throughout
SI, but esp. jejunum
Either diffusion or
carrier-mediated
transport
Binds competitively
To transferrin
(Cu, Cd, Mn, Fe)
If transferrin sites are
unavailable Albumin
& globulins
& lipoproteins
• Chromium (VI) is reduced in the stomach to
chromium(III), which lowers the absorbed
dose from ingested chromium(VI).
• Chromodulin referred to as glucose tolerance
factor (GTF), an oligopeptide complex containing four chromic ions
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 45
Factors that affect Chromium absorption
Enhancers
1. Ligands
• Methionine and Histidine
allow Cr+ to remain soluble
in alkaline pH (SI lumen)
2. Lipophilic compounds
Picolinate may aid
transport across cell
membrane
3. Vitamin C – intake of 1mg Cr+
with 100mg of ascorbate =>
plasma concentration of
chromium
Inhibitors
1. Inorganic Cr+ in an Alkaline pH
(e.g. Antacid use) leads
to absorption as Cr+
reacts with the hydroxyl
ion to form complexes
2. High levels of phytates
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 46
Chromium StorageThe chromium pool in body = 4.6 mg
Tissue storage
Kidney Liver
Muscle Spleen
Heart Pancreas
Bone
Four chromium atoms complex with chromodulin molecules
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 47
Chromium: Functions
❖ It mimics insulin
❖ Potentiates action of insulin: Chromodulin is the biologically
active form of chromium that is released in response to
insulin secretion and amplifies the insulin action via
enhancing kinase activity. It also influences GLUT 4
translocation.
❖ Chromate is another form of Ch that enhances insulin
signaling.
❖ Chromium affects gene expression and/or maintain
structural integrity of nuclear strands.
© Endeavour College of Natural Health endeavour.edu.au 48
Chromium: Functions❖ A systematic review and meta analysis reported beneficial
effects of chromium supplementation on decreasing BMI, fasting insulin and free testosterone in patients with polycystic ovary syndrome (Fazelian et al. 2017).
❖ Chromium supplementation is known to reduce blood glucose concentrations (Suksomboon, Poolsup, & Yuwanakorn, 2014).
❖ Chromium may improve metabolic syndrome and insulin resistance in diabetic and pre-diabetic individuals especially when supplemented along with Se & Mg. (Hajra et
al. 2016, Dou etal. 2016, Panchal, Wanyonyi and Brown, 2017)
© Endeavour College of Natural Health endeavour.edu.au 49
Revision Questions
❖How is chromium mainly transported through
circulation?
❖Name two other minerals which competitively
bind to this transporter protein.
❖Which vitamin increases the plasma
concentration of chromium?
❖Explain the mechanism of action of Chromium in
the prevention of diabetes and obesity.
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Sources and forms of IodineSources - Reflects soil content
Animal Plant
Seafood Bread dough (commercial)
Fruit Vegetables
Meat Water
Form
Generally found in its ionic form –
Iodide (I-) iodate (IO3-) – in iodized salt
© Endeavour College of Natural Health endeavour.edu.au 51
Factors affecting Iodine / iodide absorption
Enhancers
o Tyrosine
o Protein
o Glutathione
Inhibitors
o Goitrogens
(isothiocyanates)
• Cruciferous family (kale,
broccoli)
• Perchlorate, water
contaminant
o Selenium deficiency
o Vit A deficiency
o Iron deficiency
Thyroid
functions
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 52
Iodine Digestion & Absorption
❖Dietary iodine is either bound to amino acids
(termed organic) or found free as iodate (IO3- ) or
iodide (I-).
❖During digestion, organic bound iodine is
converted to iodide. The fortified form in the bread
is usually reduced to iodide by glutathione in the
GI tract.
❖The thyroid hormone (supplements) are absorbed
unchanged with a bioavailability of 70%.
❖Though the mechanism of its intestinal basolateral
transport unclear, its uptake by the thyroid gland is
by an active transport system. (Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 53
Iodine Digestion & Absorption
Iodide Iodide
T4
T3
Iodide
Thyroxine (T4)
Triiodo-thyroxine (T3)
Thyroid
gland
T4
T3
Simple diffusion
Food
At brush border At basolateral layer
Organic bound iodine freed via digestion. Along with the
supplement form, it is absorbed by diffusion at brush
border.
Absorbed rapidly from stomach and duodenum
Overall absorption greater than 90%
Travels as free iodide in blood
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 54
Iodine uptake by thyroid gland
Iodide
T4
T3
• 70-80% Iodide is taken up by the
thyroid gland via a Na+/ I-
symporter which is ATP dependent.
• The thyroid gland contains 70-80%
of total body iodide and is the main
site of it storage along with salivary
glands.
Na+/ I- symporter
Active TransportThyroid
gland
T4
T3
I-
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 55
Revision Questions
❖Name three nutrient deficiencies which can
affect absorption of iodine.
❖Which mechanism is utilised to allow iodine to
enter and exit the enterocytes?
❖How is iodine taken up into thyroid gland?
❖Which foods are iodine inhibitors?
❖Name three enhancers of iodine.
© Endeavour College of Natural Health endeavour.edu.au 56
Sources and forms of MolybdenumSources
o Widely distributed but varies due to soil concentration
like other minerals.
Legumes Meat
Fish Poultry
Grains Grain products
Nuts Vegetables
Fruits Dairy products
Forms found in the body
1. Mo4+
2. Mo6+
o Generally bound to sulphur or oxygen.
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 57
Molybdenum Digestion & Absorption
MoO42-
Carrier mediated
Active Transport Na+
Passive
Diffusion
Mo042-
Mo042- - Albumin
Mo42- - 2 – macro
globulin
Storage of Molybdenum
Most: Some:
▪ Liver 1. SI 4. Thyroid
▪ Kidney 2. Lungs 5. Adrenal glands
▪ Bone 3. Brain 6. Muscles
Little is known about absorption sites – stomach, small intestines (proximal more than
distal). 85-93% absorption from ingested Mo by high affinity carrier that also transports
sulphate.
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 58
Revision Questions
❖How is molybdenum transported in circulation?
❖ What are the two mechanisms of molybdenum
absorption at the intestinal brush border and
why would one method be utilised over another?
© Endeavour College of Natural Health endeavour.edu.au 59
SeleniumSources
More than any other trace element, dependent on soil concentration.
Walnut Brazil nuts
Cashews Eggs
Garlic Onions
Cereals Grains
Organ meats Seafood
(Mercury in fish decreases selenium bioavailability)
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 60
Forms of Selenium
Organic forms
Selenomethionine
Selenocystine
Selenocysteine
Se-methyl methionine
Inorganic forms
(in some vegetables)
Selenite
Selenate – thought to be better absorbed than selenites
o NB: In low soil levels –supplementation of sodium selenite in animal foods occurs
Note:
Chemically similar to sulphur – can be
substituted for sulphur in amino acids:
methionine, cysteine, cystine
Organic and inorganic forms are efficiently
absorbed
The duodenum is the primary absorption site,
same in jejunum and ileum
Selenomethionine better absorbed than selenite
and selenocysteine
Selenoamino acids = 50-80% absorption
Generally Se absorption = 44 - 70%
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 61
Factors affecting Se absorption
Enhancers
1. Vitamin A
2. Vitamin C
3. Vitamin E
4. Reduced glutathione
(GSH) in intestinal lumen
Inhibitors
1. Heavy metals (ie
Mercury) – chelates and
precipitates selenium
2. Phytates – reduces
absorption
(Gropper & Smith, 2018)
© Endeavour College of Natural Health endeavour.edu.au 62
Selenium Digestion & Absorption
Inorganic
SeO4
SeO3
Selenoamino
acids
Amino acid
Transporter Selenoamino
acids
SeO4
SeO3
Organic Selenium
Inorganic selenium
Selenate
Selenite
Chelation with heavy
metals, phytates
Excretion
Passive diffusion
Na+ dependent Active
transportunknown
AA
transporter
Once in liver majority bound to selenoprotein P.
Stored in kidneys, liver, heart, pancreas, muscles.
© Endeavour College of Natural Health endeavour.edu.au 63
Revision Questions
❖What form of selenium is thought to be better
absorbed?
❖Name two factors which increase absorption of
selenium?
❖Name two ways selenium may be transported in
circulation?
❖Name a specific protein for selenium.
© Endeavour College of Natural Health endeavour.edu.au 64
Boron
Sources
Avocado Peanuts
Peanut butter Pecans
Raisins Grapes
Meat Nuts
Fruit Vegetables
Wine Cider
Beer
Forms
1. Boric acid
2. Sodium borate (borax)
© Endeavour College of Natural Health endeavour.edu.au 65
Boron Digestion & Absorption>85% of ingested boron is rapidly
absorbed
Passive diffusion
Most boron absorbed is B(OH)3 is excreted
in the urine, with small amounts lost in
faeces and sweat. Agonist - Calcium
Boric acid
B(OH)2
Orthoboric acid
B(OH)3
Borate anion
B(OH)4
Storage
* Bone * Teeth
* Nails * Hair
Total body content = 3 - 20mg
© Endeavour College of Natural Health endeavour.edu.au 66
Revision Questions
o Boron is thought to move into and out of cells by
which mechanism?
o Where is boron found mainly in the body?
© Endeavour College of Natural Health endeavour.edu.au 67
Vanadium
Sources
Very low in foods
Fats Oils
Black pepper Parsley
Dill seed Fish sticks
Mushrooms
Shellfish
Oysters
Cereals
Grains
© Endeavour College of Natural Health endeavour.edu.au 68
VanadiumForms
1. V2+
2. V5+ - vanadate (primary form)
Storage
o Little vanadium is found in the body
o Most tissues contain vanadium – highest concentrations in:• Kidney
• Bones
• Spleen
• Liver
© Endeavour College of Natural Health endeavour.edu.au 69
Vanadium Digestion & Absorption
❖ Absorption varies due to oxidative states
❖ Vanadate is thought to be reduced to vanadyl (VO2+) in
the stomach before absorption
❖ However, vanadate is thought to be 3-5 times more
efficiently absorbed than vanadyl
❖ Overall absorption = < 10%
❖ In blood cells and plasma, found as Vandate
❖ Glutathione, NADH and ascorbic acid act as
reducing agents (vanadate → Vanadyl)
❖ In blood and liver – binds to albumin, transferrin and
ferritin, respectively
❖ Mimics the action of insulin
© Endeavour College of Natural Health endeavour.edu.au 70
Revision Questions
❖What is vanadium bound to for transport through
circulation?
❖Name two other nutrients use the same
transporter proteins as vanadium?
© Endeavour College of Natural Health endeavour.edu.au 71
Clinical issues of micromineral
metabolism
It is important that nutrition professionals are aware of the evidence for the
nutritional essentiality of micronutrients and for the situations where an
increased intake may lead to clinical benefit.
Read the following article and discuss:
❖ Implications of subclinical deficiency of folate , zinc and chromium
❖ Can excess supplementation with antioxidant prevent chronic diseases?
Shenkin, A. (2006). Micronutrients in health and disease. Postgrad Med J.
82(971): 559–567.
doi: 10.1136/pgmj.2006.047670
Access full article Here
© Endeavour College of Natural Health endeavour.edu.au 72
Activity – Make your own tableNutrient Forms Digestion Absorption Transporter
proteins
Highest
Storage
Metabolism Agonist Antagonist
Brush
border
Basolateral
border
Additional resources
http://themedicalbiochemistrypage.org/iron-
copper.php#introduction
http://quizlet.com/6335425/vitamin-and-mineral-absorbtion-flash-
cards/
© Endeavour College of Natural Health endeavour.edu.au 73
ReferencesBell, S. G., & Vallee, B. L. (2009). The metallothionein/thionein system: an oxidoreductive
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© Endeavour College of Natural Health endeavour.edu.au 76
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