Transcript Thyroid gland

Unit 9: Minerals
Topics to cover
 Definitions


Macrominerals vs microminerals
Macronutrients vs micronutrients






Calcium
Iron
Zinc
Copper
Iodine
Selenium
 General absorption of minerals
 Functions, deficiencies & homeostasis of minerals
 Antioxidants
 Why do mineral deficiencies occur? Strategies to
alleviate worldwide deficiencies
Definitions
Macrominerals vs microminerals
Macronutrients vs micronutrients
Macro vs microminerals
 Macrominerals:
 Include calcium, phosphorus, magnesium, sodium,
potassium and chloride
 Macrominerals are required in amounts greater than
100 mg/day
 Microminerals:
 Include iron, zinc, copper, selenium, chromium,
iodine, manganese, molybdenum, fluorine, nickel,
silicon, vanadium, arsenic, boron, cobalt.
 Required in small quantities
 Microminerals are also known as ‘trace elements’
Macro vs micronutrients
 Macronutrients include:
 Protein
 Lipids
 Carbohydrates
 Micronutrients include:
 Minerals (macrominerals & microminerals)
 Vitamins (fat and water soluble)
 Units 7 & 8 cover vitamins
 Unit 9 covers minerals
General absorption of
minerals
Digestion/absorption
 Unlike macronutrients (i.e. protein, fat,
carbohydrates), micronutrients do not
require enzymes for them to be
absorbed.
 Sometimes minerals are bound to
proteins, and enzymatic digestion of the
protein might help in the release of the
mineral.
 Sometimes minerals are found as salts.
pH affects absorption of some
minerals
 Some minerals (Ca, Fe, Zn, Cu) are present in foods as
insoluble salts.
 Minerals from foods are solubilized in the stomach
thanks to the acidity (HCl).
 When we take an antacid with our foods, we do not
favor the solubility and absorption of minerals. Why?
pH of stomach is increased.
 This solubility does not last long, since the intestine is
more alkaline (pH ~7).
 In alkaline environments, minerals tend to precipitate
and not be absorbed (instead are excreted).
 Precipitation of minerals will not happen depending on
the presence of certain food components that bind to
the mineral, and enhance its absorption (‘enhancers’)
 There are also mineral ‘inhibitors’.
Foods components affect the
absorption of some minerals
 Calcium absorption:
 Enhanced by lactose (sugar in milk)
 Inhibited by fiber and phytate
 Enhanced by vitamin D
 Inhibited by fat
 Iron absorption:
 Enhanced by vitamin C and meat
 Inhibited by fiber, phytate, tannins (tea), oxalate
(spinach) and certain proteins (soy protein, egg
protein, casein)
 Zinc absorption:
 Inhibited by fiber, phytate and tannins (tea) and
oxalate (spinach)
 Oxalate (or oxalic
acid) present in
foods like chocolate
and spinach binds
to minerals and
inhibits their
absorption.
 Likewise, phytate
(or phytic acid)
present in many
plant crops, is a
mineral inhibitor.
Just like certain
nutrients affect
mineral
absorption,
certain minerals
and nutrients
affect the action
of common
drugs.
Minerals might compete for
absorption at the intestinal site
 Magnesium vs calcium
 Phosphorus vs calcium
(a dietary intake of 1:1 is recommended)
 Iron vs zinc
Functions, deficiencies &
homeostasis of minerals
CALCIUM (Ca)
Calcium
 Calcium participates in important functions:
 nerve transmission
 muscle contraction
 synthesis of hormones and enzymes
 mineralization of bones
 clotting of blood
 When we don’t have enough calcium in our
blood, our bones are ‘stripped’ from their Ca.
 99% of our body Ca is in our bones.
 This can lead to osteoporosis (insufficient bone
mineralization).
Calcium homeostasis
 Regulation of calcium involves 3 hormones:
 parathyroid hormone (produced by parathyroid
gland)
 1,25-(OH)2 vitamin D3 (synthesized in kidneys)
 calcitonin (produced by thyroid gland)
 Together, they play a major role in keeping
plasma calcium levels at a constant level.
Calcium homeostasis by PTH
 When plasma calcium falls below the
normal standard (10 mg/100 mL), the
parathyroid gland secretes PTH
(parathyroid hormone).
 PTH acts on the kidney:
 It converts an inactive form of vitamin D into
the active form 1,25-(OH)2 vitamin D3 (known
as calcitriol)
 It stimulates the kidney to conserve Ca (not
eliminate it in urine)
 PTH acts on the bone:
 It stimulates the mobilization of Ca away from
the bone
Calcium homeostasis by calcitriol
 Calcitriol (1,25-(OH)2 vitamin D3) is the active
form of vitamin D
 Calcitriol acts on intestine:
 It stimulates the absorption of Ca by the intestine
 Calcitriol acts on bones:
 It mobilizes calcium away from the bone
 Estrogen enhances calcium absorption
indirectly by enhancing 1,25-(OH)2 D3
production in the kidney.
 This explain why long hormone replacement therapy
(HRT) in menopausal women appears to be valuable
in preventing bone fractures that stem from
osteoporosis.
Increased bone
resorption= increased
Ca losses from bone.
Calcium homeostasis by calcitonin
 When plasma calcium levels rise above
normal, the thyroid gland secretes
calcitonin (a hormone)
 Calcitonin functions by depositing
calcium on the bone.
 In this way, calcium levels in the plasma
go down.
 Thus, calcitonin promotes the
mineralization of bones.
IRON (Fe)
Iron
 Iron deficiency is the micronutrient deficiency most
prevalent in the world.
 It is followed by vitamin A, iodine and zinc.
 Iron is a part of heme present in:
 hemoglobin (which transports oxygen in blood)
 myoglobin (which stores oxygen in muscle)
 cytochromes involved in the electron transport chain
(unit 6) and in cytochrome P450 (involved in
metabolism of drugs, pesticides, carcinogens, alcohol
metabolism)
 Iron is also forms part of many metalloenzymes
involved in many reactions occurring in the body.
Iron deficiency
 Deficiency of iron can lead to fatigue,
anemia (where hemoglobin levels drop
below 120 g/dL), poor school performance
and poor immunity, brain function,
premature birth, death.
 Iron deficiency most evident:
 pre-menopausal women (due to menstrual
losses each month)
 pregnant women (due to expanding blood
volume)
 infants and children (rapid growth rates, thus
high Fe needs)
Ferritin
 Storage form of Fe in body is called ferritin.
 Infants are born with high ferritin levels, which
are their sources of Fe for the 1st six months of
life
 After the 6th month, when storage of Fe goes
down, pediatricians recommend feeding
complementary foods enriched with Fe (purees,
infant cereals, formulas)
 Human milk (the gold standard for infant
nutrition) not a great source of Fe (0.5 mg-0.3
mg/L), however it is more absorbable than cow
milk. Human milk Fe is 50% absorbable vs cow
milk Fe which is 10% absorbable.
To determine Fe status
 To determine the Fe status of an individual,
the following tests can be performed:
 Serum ferritin (this is proportional to the storage
levels in the body; low levels correspond to a
low Fe status)
 Problem with this test is that it is affected by
infection, fever, liver disease.
 Transferrin saturation (transferrin is the blood
protein that binds and carries Fe to the tissues;
low saturation levels mean low Fe status).
 Transferrin receptors (transferrin-Fe bind to
transferrin receptors in cells; high levels of
transferrin receptors correspond to a low Fe
status)
Toxicity
 Toxicity could occur due to (a)
oversupplementation, (b) repeated blood
transfusions, or (c) a genetic disease that
predisposes individual to absorb Fe
(hemochromatosis)
 Fe deficiency is as deleterious to human health
as iron overload.
 Why? Fe participates in the Fenton reaction,
which results in the production of free radicals.
 These free radicals damage cell membranes
(phospholipids), proteins and DNA/RNA.
Fenton reaction
Fe2+ + H2O2---> Fe3+ + .OH + OHFerrous iron
Ferric iron
Hydrogen peroxide
(common byproduct of
metabolism)
Hydroxyl anion
Hydroxyl radical
(damaging to cell membranes,
proteins and DNA)
ZINC (Zn)
Zinc
 Zinc plays key roles in growth and immunity.
 Zn deficiency leads to:
 growth failure
 susceptibility to infections
 complications during childbirth
 may be a particular problem for those with HIV
infection
 Zn supplementation of at-risk populations leads to
improved growth.
 Zn supplementation reduces the mortality of diarrheal
diseases and lowers the incidence of respiratory tract
pneumonia, two of the most common causes of death
in children in developing countries.
How to determine Zn status?
 It is difficult to determine whether a person is zinc
deficient.
 Measuring Zn levels in blood is not reliable, since zinc
changes with the time of the day. It has a circadian
rhythm. Zn levels are also affected by illness and
periods of rapid growth.
 Others methods involve:
 Measuring levels of alkaline phosphatase or alcohol
dehydrogenase in blood which are enzymes that require
zinc
 Zinc concentrations in hair
 It is difficult to diagnose Zn deficiency since
symptoms are similar to those of Fe deficiency.
Metallothionein (MT)
 Just like ferritin is the storage form of Fe,
metallothionein is the storage form of Zn in body.
 However, it is not specific to Zn since it can also
store cadmium, copper, selenium, mercury
 Metallothionein is rich in cysteine (amino acid).
 It has been hypothesized that a MT disorder explains
several symptoms of autism (the mercury poisoning
hypothesis), but a study (2006) found that autistic
children did not differ significantly from normal
children in levels of MT.
COPPER (Cu)
Copper
 This mineral participates in many reactions:
 Collagen synthesis, melanin (skin pigmentation)
synthesis, cytochromes in respiratory chain,
neurotransmitter synthesis
 Once absorbed, copper binds to
ceruloplasmin in blood. It is a Cu storage in
tissues.
 Besides acting as a Cu carrier & storage,
ceruloplasmin is involved in Fe absorption.
 Thus, Cu deficiency can lead to Fe deficiency
 Cu deficiency is rare
Wilson’s disease
 Wilson's disease is a genetic disorder in
which copper accumulates in tissues. In
this disease the individual has psychiatric
symptoms and liver disease.
 It is treated with medication that reduces
copper absorption or removes the excess
copper from the body, but occasionally a
liver transplant is required.
Menkes disease
 Menkes disease is a genetic disorder that
affects copper levels in the body, leading to
copper deficiency.
 It is characterized by sparse and coarse
hair, growth failure, and deterioration of
the nervous system.
 Also known as ‘kinky hair disease’.
 Results in death before the age of 3 yrs.
IODINE (I)
Iodine
 Iodine forms part of two hormones
synthesized by the thyroid gland.
 Tetraiodothyronine (T4)
 Triiodothyronine (T3)
 Iodine is first incorporated into the thyroid
gland, and binds to tyrosine (amino acid)
residues of the protein thyroglobulin.
 Further reactions, results in T3 and T4.
 About 90% of the hormone released by the
thyroid gland is T4, while 10% is T3.
Functions of T3 and T4
 Involved in protein
synthesis; bone growth,
neuronal maturation; cell
differentiation;
Thyroid gland regulation of protein,
carbohydrate and fat
metabolism; regulation
of vitamin metabolism.
 Increases electron
transport chain activity


This causes increased
body heat production
Increased oxygen
consumption
http://www.endocrineweb.com/thyfunction.html
Regulation of T3 and T4
 The thyroid gland is stimulated by TSH
(thyroid stimulating hormone) secreted by
the pituitary gland.
 When T4 in blood are low, pituitary gland
secretes TSH, which enlarges the thyroid gland.
 When T4 in blood are normal or high, TSH
secretion is stopped.
 The pituitary gland is in turn affected by
the hypothalamus, which secretes TRH
(thyrotropin-releasing hormone) which
enhances the synthesis and release of TSH
by the pituitary.
http://www.endocrineweb.com/thyfunction.html
Iodine deficiency disorder (IDD)
 Iodine deficiency is the most important cause
of brain damage and mental retardation.
 IDD consists of a wide spectrum of disorders
ranging from simple goiter, characterized by
an enlargement of the thyroid gland, to
cretinism, an irreversible form of mental
retardation.
 About 740 million people are affected by
goiter, and over 2 billion people are
estimated to be at risk of IDD, particularly
those living in countries where the soil and
water iodine content are low such as India,
Nepal, and China.
Goiter, characterized by an
enlarged thyroid gland.
When thyroid hormones are
low, the pituitary gland
secretes TSH which has the
effect of enlarging the
thyroid (this is to increase
the surface area to “trap”
iodine).
Particularly prevalent in
India, Nepal and China.
SELENIUM (Se)
Selenium
 Selenium is incorporated into proteins
to make selenoproteins, which are
important antioxidant enzymes.
 The antioxidant properties of
selenoproteins help prevent cellular
damage from free radicals.
 Selenium also participates in thyroid
hormone metabolism.
Glutathione peroxidase
 Selenium is an important cofactor for
the enzyme glutathione peroxidase (a
selenoprotein).
 This means that without Se the enzyme
cannot function.
 Glutathione peroxidase uses
glutathione (tripeptide made of glycine,
cysteine & glutamic acid) and catalyzes
the reduction of hydrogen peroxide
into water.
Glutathione peroxidase
Oxidized glutathione
Glutathione peroxidase
2 GSH + H2O2
GSSG + H2O
Hydrogen peroxideDamaging to cell membranes & DNA
Reduced glutathione
Water
Selenium sources (dependent on
soil content)
 The content of selenium in food depends on
the selenium content of the soil where
plants are grown or animals are raised.
 Soil in the high plains of northern Nebraska and
the Dakotas have very high levels of selenium.
 Soils in some parts of China and Russia have
very low amounts of selenium.
 Selenium also can be found in meats and
seafood. Animals that eat grains or plants
that were grown in selenium-rich soil have
higher levels of selenium in their muscle.
 Nuts are good sources.
http://ods.od.nih.gov/factsheets/selenium.asp
Antioxidants
Free radicals
 Free radicals are atoms or molecules with
an imbalance of electrons.
 Examples of free radicals are: superoxide radical
(O2-), peroxyl radical (O22-), hydrogen peroxide
(H2O2), OH. (hydroxy free radicals), HO2.
(hydroperoxyl radicals)
 They are damaging to our bodies since they
can attack DNA, proteins and
polyunsaturated fatty acids (in our cell
membranes).
 Some of these radicals result from normal
cellular processes.
Antioxidants
 What can protect our bodies from free radical attack
are the antioxidants.
 While Fe participates in the Fenton reaction that leads
to hydrogen peroxide, it can also help get rid of O2(unsafe) and convert it into O2 (safe). Thus, Fe is
considered an antioxidant.
 Other examples of antioxidants are
 Selenium (because is a cofactor of glutathione
peroxidase), vitamin C, zinc, copper &
manganese (because they are all cofactors of
superoxidase dismutase which gets rid of superoxide
radicals), vitamin E, beta carotene and other
carotenoids (lycopene).
Why do mineral deficiencies
exist?
Strategies to alleviate worldwide
deficiencies.
Why do mineral deficiencies occur?
 Poor consumption of mineral.
 High consumption of foods that inhibit their
absorption.
 Phytate (plant foods) inhibits Ca, Zn, Fe;
goigotrens (chemicals present in cassava,
cabbage, turnips) affects I metabolism; oxalates
(spinach) affects Ca & Fe
 Poor consumption of foods that enhance
their absorption.
 Citrus fruits (rich in vitamin C) enhance Fe
absorption; lactose and vitamin D (milk)
enhance Ca absorption; low consumption of
meat (enhances Fe)
Why do deficiencies occur? (contd)
 Diseases and infections
 Examples: parasite infection/bleeding can lead
to iron deficiency
 Stages of life:
 Pregnant women, infants and children (higher
needs of minerals), pre-menopausal women
(increased Fe losses through menstruation),
older people (decreased capacity to synthesize
vitamin D which increases Ca absorption),
menopausal women (lack of estrogen, estrogen
increases Ca absorption).
Strategies to alleviate worldwide
micronutrient deficiencies
 Education of the population
 Supplementation (providing mineral pills)
 Acceptability?
 Distribution?
 Economically available?
 Fortification of foods (i.e. enriching foods
with minerals)
 Infrastructure/technology available?
 Important to consider which food vehicle will be
fortified
Factors to consider when fortifying
a food: a proper food vehicle
 The success of a fortification program
depends, in large part, on the selection of
the right food vehicle.
 The FAO (Food and Agriculture
Organization) has established requirements
for a potential food vehicle:
 should be commonly consumed by the target
population
 should be consumed in adequate amounts but
with a low risk of excess consumption
 should be affordable
 should have good stability during storage
Examples of common fortification
of foods:
•
•
•
•
Calcium-fortified food: orange juice (USA)
Iodine-fortified food: salt
Iron-fortified foods: soy sauce (China), salt (India),
fish sauce (Vietnam and Thailand), wheat flour (many
countries), corn and wheat flour (Mexico), rice
(Japan), and milk (Argentina and Chile)
Zinc-fortified foods: wheat flour (sometimes
co-fortified with iron, vitamin B1, B2 and folic
acid) (India, Vietnam, China, Pakistan), wheat
noodles (Thailand), wheat (Peru, Mexico) and maize
(Mexico) flour, and milk (Chile).
Strategies (contd)
 Bio-fortification:
 Aim at fortifying crops (potatoes, rice,
wheat, cassava, bananas, corn) with
minerals in which they are deficient.
 Breed plants with increased levels of
enhancing components:
 Vitamin C (Fe), amino acids (Zn, Fe),
etc
Strategies (contd)
 Biofortification (contd)
 Breed plants with decreased levels of
inhibiting components:
 Example: corn with decreased levels of
phytate (phytate inhibits absorption of Ca,
Fe, Zn)
 Spinach with decreased levels of oxalate