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© Endeavour College of Natural Health endeavour.edu.au 1 NMDF211 Nutritional Biochemistry Micromineral Pharmacokinetics Session 4

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Page 1: NMDF211 Nutritional Biochemistry · NMDF211 Nutritional Biochemistry Micromineral Pharmacokinetics ... ferric/cupric reductase in the presence of acidic environment and vitamin C

© Endeavour College of Natural Health endeavour.edu.au 1

NMDF211

Nutritional Biochemistry

Micromineral Pharmacokinetics

Session 4

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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

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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)

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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)

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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)

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Trace minerals

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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)

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Copper Absorption

(Copyright, Cengage 2018, Gropper & Smith, 2018)

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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).

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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)

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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)

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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+

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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)

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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.

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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)

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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.

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(copyright@Cengage, Gropper & Smith, 2018)

Iron Digestion & Absorption

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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

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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?

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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)

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❖ 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)

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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)

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• 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

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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.

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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.

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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)

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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

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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)

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Revision Questions

o Name two ways manganese is transported

through circulation?

o Iron competes for absorption with manganese.

Why may this be the case?

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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)

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Zinc Digestion and Absorption

(Gropper & Smith, 2018)

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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)

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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)

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Zinc: Functions

• Cofactor for several

enzymes

• Growth - regulation of

transcription

• Cell replication

• Bone formation

• Skin integrity

• Cell-mediated immunity

• Generalized host defense

• Carbohydrate metabolism

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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.

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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)

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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?

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Ultratrace minerals

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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)

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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)

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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)

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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)

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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)

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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)

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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.

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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)

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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

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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)

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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)

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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)

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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)

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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.

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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)

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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)

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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?

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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)

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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)

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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)

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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.

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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.

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Boron

Sources

Avocado Peanuts

Peanut butter Pecans

Raisins Grapes

Meat Nuts

Fruit Vegetables

Wine Cider

Beer

Forms

1. Boric acid

2. Sodium borate (borax)

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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

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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?

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Vanadium

Sources

Very low in foods

Fats Oils

Black pepper Parsley

Dill seed Fish sticks

Mushrooms

Shellfish

Oysters

Cereals

Grains

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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

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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

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Revision Questions

❖What is vanadium bound to for transport through

circulation?

❖Name two other nutrients use the same

transporter proteins as vanadium?

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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

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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/

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ReferencesBell, S. G., & Vallee, B. L. (2009). The metallothionein/thionein system: an oxidoreductive

metabolic zinc link. Chembiochem: A European Journal of Chemical Biology,

10(1), 55-62. doi:10.1002/cbic.200800511

Chasapis, C. T., Loutsidou, A. C., Spiliopoulou, C. A., & Stefanidou, M. E. (2012). Zinc

and human health: an update. Archives of Toxicology, 86(4), 521-534.

doi:10.1007/s00204-011-0775-1

Dou, M., Ma, Y.,Ma, A.G., Han, L., Song, M.M., Wang, Y.G., Yao, M.X.,Sun, X.F.,Li,

Y.,Gao, S., Zhang, Y. (2016). Combined chromium and magnesium decreases

insulin resistance more effectively than either alone. Asia Pac J Clin Nutr,

25(4):747-753. doi: 10.6133/apjcn.092015.48.

Ems, T., Huecker, M. R. (2019). Biochemistry, Iron Absorption. In: StatPearls [Internet].

Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from:

https://www.ncbi.nlm.nih.gov/books/NBK448204/

Fazelian, S., Rouhani, M.H., Bank, S.S., Amani, R. (2017). Chromium supplementation

and polycystic ovary syndrome: A systematic review and meta-analysis. J Trace

Elem Med Biol, 42:92-96. doi: 10.1016/j.jtemb.2017.04.008.

Gropper, S. S., & Smith, J. L. (2013). Advanced nutrition and human metabolism (7th

ed.). Belmont, CA: Wadsworth Cengage Learning.

Hajra, B.,Orakzai, B.A.,Faryal, U., Hassan, M.,Rasheed, S.,Wazir S. (2016). Insulin

Sensitivity To Trace Metals (Chromium, Manganese) In Type 2 Diabetic Patients

And Non Diabetic Individuals J Ayub Med Coll Abbottabad.;28(3):534-536.

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© Endeavour College of Natural Health endeavour.edu.au 74

ReferencesHoey, L., Strain, J. J., & McNulty, H. (2009). Studies of biomarker responses to

intervention with vitamin B-12: a systematic review of randomized

controlled trials. The American Journal of Clinical Nutrition, 89(6), 1981S-

1996S. doi:10.3945/ajcn.2009.27230C

Hurrell, R. F., Reddy, M., & Cook, J. D. (1999). Inhibition of non-haem iron absorption in

man by polyphenolic-containing beverages. The British Journal Of Nutrition,

81(4), 289-295. Retrieved from

https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.

com/login.aspx?direct=true&db=rzh&AN=107085712&site=eds-live&scope=site

McMurry, J. (1992). Organic chemistry (3rd ed.). Pacific Grove, CA: Brooks/Cole

Publishing Company.

Marks, D. B., Marks, A. D., & Smith, C. M. (1996). Basic medical biochemistry – a

clinical approach. Baltimore, MD: Lippincott Williams & Wilkins.

Roohani, N., Hurrell, R., Kelishadi, R., & Schulin, R. (2013). Zinc and its importance for

human health: An integrative review. Journal of research in medical sciences:

the official journal of Isfahan University of Medical Sciences, 18(2), 144.

Osiecki, H. (2002). Cancer: A nutritional/biochemical approach. Eagle Farm, QLD:

Bioconcepts Publishing.

Panchal, S.K., Wanyonyi, S., Brown, L. (2017). Selenium, Vanadium, and Chromium as

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doi: 10.1007/s11906-017-0701-x.

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© Endeavour College of Natural Health endeavour.edu.au 75

References

Prosser, N., Heath, A., Williams, S., & Gibson, R. (2010). Influence of an iron intervention

on the zinc status of young adult New Zealand women with mild iron deficiency.

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.

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