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TRACE MINERALS ( Zinc, Selenium, Boron and
                Cobalt)

Ms. Latika Yadav (Research Scholar), Dept. of Foods and Nutrition, College
    of H.Sc,Maharana Pratap University of Agriculture and Technology,
     MPUAT, Udaipur, rajasthan-313001, email.id: a.lata27@gmail.com
MICRO NUTRIENTS
Micronutrients are nutrients required by humans and other living
things throughout life in small quantities to orchestrate a whole
range of physiological functions, but which the organism itself
cannot produce. For people, they include dietary trace minerals in
amounts generally less than 100 milligrams/day as opposed to
macrominerals which are required in larger quantities.
The microminerals or trace elements include at least iron, cobalt,
chromium, copper, iodine, manganese, selenium, zinc and
molybdenum.


Micro nutrient elements or trace elements, are present less
than0.005% (50ppm) of the body weight. It is essential that the term
“trace” not be interpreted to mean “unimportant”.
Micronutrients are generally divided into 2 groups:
1) Trace minerals: that includes Iron, Copper, and Zinc.
2) Ultra trace minerals :includes Chromium, Manganese, Flouride,
   Iodide, Cobalt, selenium, Silicon, Arsenic, Boron, Vanadium, Nickel,
   Cadmium, Lithium, Lead and Molybdenum.


Minerals explained in my presentation are:
1) Zinc
2) Selenium
3) Copper and
4) Boron.
1. ZINC
Overview:

• 30th element in the periodic table (IIB element)
   – MW = 65.37, completely filled d orbitals
• In aqueous solutions
   – One oxidation state, namely Zn2+
   – Prefers tetrahedral complex formation
• Not a redox active metal
   – readily complexes with amino acids, peptides, proteins and
      nucleotides
   – affinity for thiols, hydroxy groups & ligands with electron-rich
      nitrogen donors
• Approximately 300 enzymes are associated with zinc
• Biological functions of Zn are divided into three categories
   – Catalytic, Structural, Regulatory
FUNCTIONS OF ZINC
1.) Zinc-containing enzymes : serving as an essential cofactor

    •More than 70 enzymes
       •Secondary & tertiary protein structures
            •Metal stabilized active sites

    •Examples of general types of enzymes requiring Zn as
    cofactor:

        Dehydrogenases
        Anhydrase
        Polymerases
        dismutases
        phosphatases
        peptidases
        kinases
        deaminases
2. Zn: Nuclear transcription factors (>130)
    •Same protein structural role forms “zinc-fingers”
    •“Zn-fingers” bind DNA
        •allow different nuclear hormones to interact with
        DNA via different DNA binding proteins
             •up to 37 “fingers” have been found on a single
             transcription factor
             •Vit. A, Vit. D, steroid hormones, insulin-like
             growth factor-1, growth hormone, and others
             bind to zinc-finger proteins to modulate gene
             expression.
        •Zn is responsible for thymidine incorporation

3. Cu/Zn Superoxide Dismutase
    General class of enzymes that protect against oxidative
    damage in the body.

4. Insulin
     Zn important structurally
     Zn needed for insulin “stored” in pancreas
         Functionality drops rapidly so more of a “working
         store” than a static store
Transcription Factors
•   Transcription factors
     – Regulate gene expression
     – Involved in virtually all biological processes:
         • Development, differentiation, cell proliferation,
            response to external stimuli
     – Consists of 2 domains
         • DNA Binding Domain (DBD) – recognizes and
            binds to specific DNA sequence elements in the
            promoter of target genes
         • Protein-interacting Trans activation Domain (TAD)
            – influences the rate of transcription.
•   Revelation
     – Gene expression is controlled by specific proteins call
       transcription factors
         • Zinc containing transcription factors account for
            1% of genome
     – Zinc plays key structural role in transcription factor
       proteins
     – Ligands for transcription factors include:
         • Vitamin A
         • Vitamin D
         • Bile acids
         • Thyroid hormones
Zinc Finger Proteins
•   Zinc finger proteins are characterized by their
    utilization of zinc ions as structural components

•   C2H2 zinc finger binding motif
     – Predominant motif in eukaryotic
       transcription
     – Involved in skeletal differentiation
     – Zinc binding motif is determined by the          Zinc-finger
       presence of 2 cysteine and 2 histidine           Interacting with DNA
       residues that engage in a four coordinate
       bond with a singe Zn ion
     – Bind to response elements in the upstream
       promoters of genes transcribed by RNA
       poly 2
     – Binds to 5S ribosomal RNA gene, and 5S
       RNA, and activates transcription by RNA
       polymerase 3.
Membrane Stability
•   Membrane fractions contain high concentrations of Zn
     – Increases rigidity of cell
•   Protection from oxidative damage
     – Competition for binding sites with redox metals
Membrane Function
In deficient animals:
     – Failure of platelet aggregation
          • Due to impaired Calcium uptake
     – Peripheral neuropathy
          • Brain synaptic vesicles exhibit impaired calcium uptake
     – Increased osmotic fragility in RBCs
          • Decreased plasma membrane sulfhydryl concentration
          Immune Function
•   After Zinc depletion
     – All functions within monocytes were impaired
     – Cytotoxicity decreased in Natural Killer Cells
     – Phagocytosis is reduced in neutrophils
     – Normal function of T-cells are impaired
     – B cells undergo apoptosis
•   High Zn supplementation shows alterations in cells similar to Zn depletion
Whole Body Fluxes


                       Plasma/Serum 2.4
                               mg                 Target tissues
    Diet Zn++
                       a-2 macroglobulin            Including
   4-15 mg/da
                             (30%)                    Liver
   (~0.15 mM)
                            albumin                   1.2 g
                             (60%)
       Intestine
Zn++ (50-100mM)                                       Milk: 2-3 ug/mL
      1-2 mg/da         Pancreatic &
  Metallothionine         Biliary             Other Losses:
                         Excretion:           Sweat, Skin, Hair up to
 Chelating Agents
                                               1 mg/da
       Phytates          4-5 mg/da
                                              Seminal Fluid: 196 ug/mL

                                            Menstrual Loss: 0.1-0.5 mg

  Feces: 3-14 mg/da                        Urine: 0.4-0.6 mg/da
Absorption


• Absorption takes place throughout the intestine
   – Primarily in the jejunum
   – Some absorption in the rumen
   – No measurable amounts absorbed from stomach
      cecum or colon
• In small intestine
   – Nonmediated (nonsaturable) process
        • Not affected by dietary Zn intake
   – Mediated (saturable) process
        • Stimulated by Zn depletion
Absorption
            Mucosa                              Serosa
                        NSBP
                                      CRIP                Zn++-Albumin

      Zn++             Zn++
 Saturable =
   Bound to                          CRIP-Zn             Albumin
form transport         MTI-Zn
    ligand                                                  Zn++-Albumin
                                  MTI
    Zn++                                                 Zn++
                 Non-saturable = Passive Diffusion


        CRIP=cysteine-rich intestinal protein; MTI=metallothionine;
                   NSBP, non-specfic binding protein
Dietary Factors that Affect Zn Absorption

• Feed/Food source                 •   Presence/Absence of other
                                       divalent cations
• Phytate (calcium-phytate-zinc          – Fe, Ca
  complex)                         •   Efficiency of absorption can vary
   – Mainly hexa- and                  from 15-60%
     pentaphosphate derivatives          – Under normal conditions 1/3 of
   – Highly dependent on calcium            dietary Zn is absorbed
                                         – Zn status alters efficiency of
• Amino Acids                               absorption
   – histidine, cysteine           •   Uptake and retention is > in
                                       growing animals
Transport in blood
• Plasma contains approx .1% of the total zinc of the body
• Albumin is major portal carrier
• Binds to albumin by tetrahedral ligation to sulfur atoms
   – 70% of Zn is bound to albumin in plasma
   – 20-30% bound to α-2 macroglobulin
   – Other plasma proteins
       • Transferrin, histidine-rich glycoprotein, metallothionine
• Plasma Zn concn’s respond to external stimuli
   – Intake fluctuations
   – Fasting
   – Acute stresses
       • infection
• Plasma Zn levels do not influence absorption from mucosa
• Most reductions in plasma levels reflect increased hepatic uptake
   – Hormonal control
Excretion
•   Lost via hair, sweat, desquamation, bile pancreatic secretions, seminal fluid, urine,
    feces
•   Main endogenous loss
     – Secretions into gut
          • Bile and pancreas
     – Mucosal cells
•   Urinary and integumental losses
          • < 20% under normal conditions
              – Losses increase with trauma, muscle catabolism, and administration of
                 chelating agents (EDTA)
•   Primarily in fecal material
     – Unabsorbed Zn
     – Secreted Zn (endogenous sources)
          • From pancreatic and intestinal
Regulation
•   Metallothionein
      – Concentrated in liver, kidney, pancreas, intestine
      – Acts as a Zn2+ buffer
           • Controls free Zn2+ level
           • Control intracellular Zn pool responsive to both hormones and diet
•   Zn-binding protein, metallothionein (MT), is involved in the regulation of Zn
    metabolism
•   MT is inducible by dietary Zn via the metal response element (MRE) and MTF-1
    mechanism of transcriptional regulation
      – ↑ in cellular MT  ↑ Zn binding within cells
•   Acute infections associated with proinflammatory cytokines increses Zn uptake into
    liver, bone marrow and thymus and reduces the amount going to bone, skin and
    intestine
Storage

•   Storage sites
     – No specfic storage sites are recognized
         • Within cells, amounts sequestered within metallothionine could be
           considered as stores
         • Anorexia, muscle catabolism, tissue zinc release
              – Metalloenzymes cling tenaciously to zinc
     – Serum/plasma zinc drops rapidly (~1 week) with zinc deficient diet
         • Zinc turnover is extensive and rapid
              – Two-components of turnover, fast ~12.3 days, and slow, ~300
                 days
         • Fast pool is also called the “exchangeable” pool
              – Usually amounts to 157-183 mg Zn
Interactions
•   Copper: - High Zn diets reduce Cu absorption
        • electronic configuration competition
     – Metallothionine synthesis induced
        • sequesters Cu in mucosal cell preventing serosal transfer
             – Happens with 150mg Zn for two years
             – Can be used with Wilson’s disease patients
             – High copper diets do not interfere with Zinc absorption
•   Iron: Supplements inhibit zinc absorption
          • Ferrous > Ferric, heme no effect
          • Pregnant and taking >60mg Fe/day should also take Zn
•   Calcium: High Ca diets reduce Zn absorption
          • effect enhanced in phytate rich diets
          • not sure how much of a problem in humans
               – post menopausal women yes, adolescent girls, no
•   Other:
     – Tin (Sb), not usually high in diet, but diets high in Tin can increase fecal Zn
       excretion
     – Cadmium (Cd), alter Zn distribution in body rather than altering absorption
     – Folic acid, conjugase requires Zn
         • High doses sometimes impair Zn status further in low Zn situation -
           mechanism currently unclear
Mechanisms of Toxicity
•   Excess accumulation within cells may disrupt functions of biological molecules
     – Protein, enzymes, DNA
          • Leads to toxic consequences
•   Anemia
     – Impaired copper availability
•   Acute excessive intakes
     – Local irritant to tissues and membranes
          • GI distress, nausea, vomiting, abdominal cramps, diarrhea
•   Relatively non-toxic
     – Sources of exposure – drinking water, feed, polluted air
Deficiency
• Signs                                     •   More signs
   – Growth retardation
                                                 – Night blindness
   – Delayed sexual maturation &
     impotence                                   – Impaired taste (hypoguesia)
        • Impaired testicular development        – Delayed healing of wounds, burns,
   – Hypogonadism & hypospermia                    decubitus ulcers
   – Alopecia                                    – Impaired appetite & food intake
   – Acroorifical skin lesions                   – Eye lesions including photophobia
        • Other, glossitis, alopecia & nail        & lack of dark adaptation
          dystrophy
   – Immune deficiencies
   – Behavioral changes
Sources
•   Relatively abundant mineral
     – Good sources: shellfish, beef and other red meats
     – Slightly less good: Whole-grains
     – most in bran and germ portions
         • 80% lost to milling
         • phytates, hexa & penta phosphates depress absorption
             – P/Zn ratios of 10 or more
     – Relatively good sources: nuts and legumes
•   Eggs, milk, poultry & fish diets lower than pork, beef, lamb diets
     – High meat diets enhance absorption
         • 280g or 10 oz fits right into food pyramid guide
         • cys & met form stable chelate complexes
2010 RDA
                                Adult:
Children
                                   Men: 12mg/day
    1-3 yrs: 5 mg/day              Women: 11mg/day
    4-6 yrs: 7 mg/day
    7-9 yrs:8mg/day                Pregnancy and lactation :
                                   12mg/day
    Boys: 10-12 yrs: 9mg/day
         13-15 yrs:11mg/day
          16-17 yrs:12mg/day

    Girls :10-12 yrs:9mg/day
          13-15 yr:11mg/day
           16-17 yrs:12mg/day
2. SELENIUM


•Selenium as a metal was first reported by Berzelius in 1817 and occur
in nature in variety of forms and colours.
•Selenium is frequently found in combination with lead, copper,
mercury and silver. These combinations are called selenides.
•Selenium is an allotropic metal in group 6 of the fourth period of the
periodic table. Its molecular weight is 78.96 Da and its atomic weight is
34.
•Selenium has 26 isotopic forms, only 5 of these are naturally occuring:
Se76,Se78,Se77,Se80,Se82.Of the radioisotopes.
•Se and Vit.E both play important roles in the detoxification of peroxide
and free radicals.
FUNCTIONS OF SELENIUM:

1. Component of glutathione peroxidase
    • catalyzes removal of hydrogen
       peroxide
GSH + H2O2               GSSG + H2O
GSH = reduced glutathione
GSSG = oxidized glutathione

2. Component of iodothyronine-5’- deiodinase
     • Converts T4 to T3
3. Improves killing ability of neutrophils
     • Reduces the prevalence and severity
        of mastitis

4.Protects cells from auto oxidative damage
Shares this role with vitamin E
    5.) Important antioxidant
Relationship of glutathione peroxidase,selenium,
                  and vitamin E




                              GSH peroxidase
                              contains selenocysteine
Selenoproteins: Enzyme Activities

1.   At least 25 selenoproteins have been identified in human biochemistry.
2.   Glutathione peroxidase (GPx) has been the functional parameter used for
     the assessment of Se status. GPxs catalyze the reduction of peroxides that
     can cause cellular damage.
3.   Thioredoxin reductase (Trx R) provides reducing power for several
     biochemical processes and defends against oxidative stress.
4.   Selenoprotein P, the majority of the Se found in the bloodstream, acts as an
     antioxidant enzyme.
5.   Selenoprotein W may play a role in oxidant defense.
6.   The peroxiredoxins (Trx PX) define an emerging family of peroxidases
     able to reduce hydrogen peroxide and alkyl hydroperoxides.
7.   Selenophosphate synthetase is an enzyme required for the incorporation of
     selenocysteine into selenoproteins.
ABSORPTION, METABOLISM AND EXCRETION
Absorption is very efficient , with most of the ingested selenium absorbed
readily from a variety of food stuffs. The source of the mineral can have
effects on its absorption.
Se is transported from the gut on the VLDL and LDL : Red cells, liver,
spleen, muscles, nails, hair and tooth enamel all contain significant
quantities of the mineral.
DAILY SELINIUM FLUX IN A 70 KG MAN                                  Sweat, skin
                                                                    loss ~ 80 μ
                                                                    g/day
   Diet 6-                            Plasma VLDL,or
                                      LDL, 0.5-2.0g/ml                       Feces ~ 50
   200μg/day
                                                                             μ g/day
                                      (50-200 μ g/L)

                                                                    Urine~ 50 μ
                                                                    g/day
                                     Selenoproteins in
                                     tissues
Food Sources
        Food content tends to follow Se content of soil – richest food
        sources are organ meats and sea foods, followed by cereals and
        grains, dairy products, fruits and vegetables
        Se content of grains can vary by 10,000 fold
•   Requirements determined based on serum glutathione peroxidase
    activity.
•   The NAS-NRC has recommended that an intake no less than 50 and no
    mare than 200g/day should be sufficient to meet need of average adult.

               Selenium Deficiency Diseases
•   Major problem in livestock
•   Human deficiency is rare except in areas with low Se content in soil
        Keshan disease occurs in Keshan China: endemic cardiomyopathy and
        muscle weakness (due to oxidized lipids)
        Aggressive supplementation has eliminated disease
•   Iatrogenic deficiency
        TPN without supplemental Se
Selenium Toxicity

•   Range of dietary Se intake
    without toxicity is narrow
•   Acute selenium poisoning
    can result in cardiorespiratory
    collapse
•   Chronic toxicity (selenosis)
    changes in nail structure and
    loss of hair
•   Hair and nail brittleness
•   Se toxicity in farm animals is
    characterized by Hoof loss
    and a neuromascular
    condition known as “Blind
    Staggers”.
Selenium and Cancer Prevention
•   Epidemiologic evidence indicates low intakes of Se are associated with higher
    risk of prostate cancer
•   Prospective study of Se supplementation demonstrated 42% reduction in cancer
    incidence
•   Small sample size and other confounding factors have diminished enthusiasm
    for the results of these studies.
•   In 1977, Gerhard Schrauzer and his team reported that Se is a potential
    human cancer-protective agent.

•   Later human epidemiological studies indicate a statistically significant inverse
    relationship between Se level and risk of cancer overall, particularly in men.
    Moreover, clinical trials showed that supplemental Se reduced the incidence
    and mortality of several types of human cancers.

•   In the 1980s, the birth of synthetic organoselenium derivatives as cancer
    chemopreventive agents in laboratory rodents was reported by Karam El-
    Bayoumy.

•   Currently two clinical invention trials in the U.S. (Selenium and Vitamin E
    Cancer Prevention Trial, SELECT), Phase III, and in Europe (Prevention of
    Cancers by Intervention with Selenium, PRECISE) are in progress.
3. BORON
•Boron is the chemical element with atomic number 5 and the
chemical symbol B. Because boron is produced entirely by cosmic ray
spallation and not by stellar nucleosynthesis,[6] it is a low-abundance
element in both the solar system and the Earth's crust. However, boron
is concentrated on Earth by the water-solubility of its more common
naturally occurring compounds, the borate minerals. These are mined
industrially as evaporate ores, such as borax and kernite.
•Boron was shown to be an essential element for plants early this
century and there is now evidence that it is also necessary for humans.
Boron is distributed throughout the human body with the highest
concentration in the bones and dental enamel.
•Prior to 1981, boron was not considered an essential nutrient; boron
was first shown to be an essential mineral for growing chicks. It was
not until 1990 that boron was accepted as an essential nutrient for
humans.
FUNCTIONS OF BORON:
•   Boron seems to be essential for healthy bone and joint function, possibly via
    effects on the balance and absorption of calcium, magnesium and
    phosphorus. It seems to affect cell membranes and the way signals are
    transmitted across these membranes.

•   Boron affects the metabolism of steroid hormones and may also play a role in
    converting vitamin D to its more active form, thus increasing calcium uptake
    and deposition into bone. Boron also increases male sex hormone levels.
•   Boron is required for the maintenance of bone and normal blood levels of
    estrogen and testosterone; within eight days of supplementing boron women
    lost 40 percent less calcium, 33 percent less magnesium and less
    phosphorus through their urine.
1. Through reactions with certain bio substances to maintain proper cell
   membrane function or stability and influences hormone reception and
   transmembrane signaling.
Absorption and metabolism
Boron is efficiently absorbed and excreted in the urine.


Deficiency

•Boron deficiency seems to affect calcium and magnesium metabolism, and affects
the composition, structure and strength of bone, leading to changes similar to those
seen in osteoporosis.
•This is likely to be due to decreased absorption and increased excretion of calcium
and magnesium.
•Boron deficiency combined with magnesium deficiency appears especially
damaging in cases of osteoporosis. Due to its effects on calcium and magnesium
metabolism, boron deficiency may also contribute to the formation of kidney
stones. Boron deficiency also seems to decrease mental alertness.

•There may also be a link between boron deficiency and osteoarthritis.
Dietary need and sources

Human requirement of Boron most likely between 0.5 and 1.0 mg/day; rich food
sources include noncitrus fruits, leafy vegetables, nuts, pulses and legumes.




Boron toxicology

Toxic effects appear at intakes of about 100 mg. The World Health Organization
has banned boron (in the form of boric acid) as a food additive and preservative.
Toxic effects include a red rash with weeping skin, vomiting, diarrhea
characterized by a blue green color, depressed blood circulation, coma and
convulsions. A fatal dose in adults is 15 to 20 g and in children 3 to 6 g. Repeated
intakes of small amounts can cause accumulative toxicity. Signs of toxicity include
nausea, vomiting, diarrhea, dermatitis, and lethargy. In addition, excess boron
intake induces riboflavinuria. Landauer found that boron-induced teratogenic
problems include skeletal abnormalities and were reduced with riboflavin therapy.
Supplements

Sodium borate is the most common form of supplement.
Boron is increasingly used in calcium and bone-
replenishing nutritional formulas. It may be particularly
useful in those whose magnesium intake is low. This
effect may be useful in the prevention of kidney stones.
Because of its effect on testosterone levels, boron
supplements have been marketed to athletes on the
basis of their ability to increase muscle mass and
strength. A 1994 study of the effects on ten male
bodybuilders did not find any increases in those with
boron supplements.
Therapeutic uses of supplements

Boron may be beneficial in the treatment of osteoporosis.
Supplements of around 3 mg per day have been shown to
enhance the effects of estrogen in postmenopausal women.
This is likely to contribute to its beneficial effects on bone
health.
Studies done in 1994 on athletic college women suggest that
boron supplements decrease blood phosphorus concentration
and increase magnesium concentration. Both of these
changes are beneficial to bone-building.Because of its sex
hormone-enhancing effects, boron may help to protect against
atherosclerosis.

Osteoarthritis
Boron supplements of 6 to 9 mg per day have been used to
treat osteoarthritis with some improvement of symptoms.
Boron content in arthritic bones may be lower than that of
normal bones and extra boron may increase bone hardness.
Interactions with other nutrients

•boron is an essential element and that it is involved in regulating
parathormone action. Therefore, it is likely that boron influences the
metabolism of calcium, phosphorus, magnesium and cholecalciferol.

•Animal studies have indicated that cholecalciferol deficiency
enhances the need for boron, and that boron might interact in some
manner other than through an effect on cholecalciferol metabolism.

•The relationship seemed strongest between boron and magnesium,
because boron supplementation alleviated magnesium deficiency
signs in chicks. Boron does not seem to consistently alleviate signs
of calcium and phosphorus deficiency.

•Boron and boron compounds can influence calcium metabolism,
and tissue boron level changes in animals with abnormal calcium
metabolism. In humans, a low caries incidence has been associated
with adequate boron levels; however other studies indicated that high
levels of orally administered boron increased dental caries.
4. COBALT:
Cobalt is another essential mineral needed in very small
amounts in the diet. It is an integral part of part of vitamin B12,
cobalamin, which supports red blood cell production and the
formation of myelin nerve coverings. Some authorities do not
consider cobalt to be essential as a separate nutrient, since it is
needed primarily as part of B12, which is itself
essential.Cobalt, as part of vitamin B12, is not easily absorbed
from the digestive tract. The body level of cobalt normally
measures 80-300 mcg. It is stored in the red blood cells and the
plasma, as well as in the liver, kidney, spleen, and pancreas .

Sources: Cobalt is available mainly as part of B12. There is
some question as to whether inorganic cobalt is actually usable
in the human body. Meat, liver, kidney, clams, oysters, and
milk all contain some cobalt. Ocean fish and sea vegetables
have cobalt, but land vegetables have very little; some cobalt is
available in legumes, spinach, cabbage, lettuce, beet greens,
and figs.
Functions: As part of vitamin B12, cobalt is essential to red
blood cell formation and is also helpful to other cells.

Uses: Cobalt, as part of B12, is used to prevent anemia,
particularly pernicious anemia; vitamin B12 is also
beneficial in some cases of fatigue, digestive disorders, and
neuro-muscular problems. There are no other known uses
except for the radioactive cobalt-60 used to treat certain
cancers.

Deficiency and toxicity: Toxicity can occur from excess
inorganic cobalt found as a food contaminant. Beer drinker's
cardiomyopathy (enlarged heart) and congestive heart
failure have been traced to cobalt introduced into beer
during manufacturing. Increased intake may affect the
thyroid or cause overproduction of red blood cells,
thickened blood, and increased activity in the bone marrow.
.
Requirements: No specific RDA is suggested for cobalt. Our needs are
low, and vitamin B12 usually fulfills them. The average daily intake of
cobalt is about 5-8 mcg. It is not usually given in supplements.

Absorption and bioavailability:
The extent of gastrointestinal absorption of cobalt depends upon the
dose, with very low doses being almost completely absorbed, whereas
larger doses are less well absorbed. Nutritional factors also influence
absorption, for example, absorption is reduced by amino acids, and
increased in iron deficiency.

Distribution and metabolism:
In human autopsy studies, the liver (the organ where vitamin B12 is
stored) contains the highest concentration of cobalt (approximately 20%
of the total body content). In the human body there is no evidence of
accumulation of cobalt with age.

Excretion:
Cobalt is mainly excreted in the urine but also in the faeces. Independent
of the route of exposure, most cobalt is eliminated rapidly, with a small
proportion being eliminated slowly and having a half-life of the order of
years.
studies related to cobalt:

Human data
Seghizzi et al., 1994
A review of the literature from the 1960s described endemics of cardiomyopathy
with mortality rates of up to 50 % in heavy consumers of cobalt-fortified beer
(containing cobalt concentrations of 1 – 1.5
ppm). The intake of cobalt in such consumers was estimated to be 6 – 8 mg daily.
Dietary protein deficiency may be an important factor in cobalt induced
cardiomyopathy, and zinc and magnesium deficiency may also play a part.
Animal data
Pedigo et al., 1988
Cobalt chloride was administered to groups of 10 mice in drinking water providing
23, 42 or 72 mg cobalt/kg bw/day for up to 13 weeks. The highest dose level
resulted in a dose- and time-dependent decrease in testicular weight and
decreased epididymal sperm concentration, along with decreases in both motility
and percent motile forms of sperm. Fertility was decreased at week 13. There was
a dosedependent decrease in testicular weights (as a ratio to body weight), whilst
serum testosterone levels were increased 5 to 7 fold at all dose levels.
REFERENCES:

1. Berdanier .C.D., Advanced Nutrition Micronutrients. CRC Press.
2. Shils et al., Modern Nutrition in the health and Disease. Lippincott
   Williams & wilkins, New York. 2006.
3. Stump et al., Krause’s Food & Nutrition Therapy. Saunders Elsevier.
   International edition. 2008.
4. Guthrie., Introductory Nutrition .The C.V. Mosby Company.5th
   edition , 1983.
5. Stipanuk.H.Martha., Biochemical and Physiological aspects of
   Human Nutrition, Saunders Elsevier.2000.
6. http://www.dcnutrition.com/minerals/detail.cfm?RecordNumber=47
7. http://jctonic.com/include/minerals/boron.htm
8. http://www.fasebj.org/content/1/5/394.short
9. http://en.wikipedia.org/wiki/Boron
10. http://www.healthy.net/scr/article.aspx?Id=2051
11.http://www.food.gov.uk/multimedia/pdfs/evm_cobalt.pdf
12.http://en.wikipedia.org/wiki/Cobalt.
trace minerals, Zn, Co

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trace minerals, Zn, Co

  • 1. TRACE MINERALS ( Zinc, Selenium, Boron and Cobalt) Ms. Latika Yadav (Research Scholar), Dept. of Foods and Nutrition, College of H.Sc,Maharana Pratap University of Agriculture and Technology, MPUAT, Udaipur, rajasthan-313001, email.id: a.lata27@gmail.com
  • 2. MICRO NUTRIENTS Micronutrients are nutrients required by humans and other living things throughout life in small quantities to orchestrate a whole range of physiological functions, but which the organism itself cannot produce. For people, they include dietary trace minerals in amounts generally less than 100 milligrams/day as opposed to macrominerals which are required in larger quantities. The microminerals or trace elements include at least iron, cobalt, chromium, copper, iodine, manganese, selenium, zinc and molybdenum. Micro nutrient elements or trace elements, are present less than0.005% (50ppm) of the body weight. It is essential that the term “trace” not be interpreted to mean “unimportant”.
  • 3. Micronutrients are generally divided into 2 groups: 1) Trace minerals: that includes Iron, Copper, and Zinc. 2) Ultra trace minerals :includes Chromium, Manganese, Flouride, Iodide, Cobalt, selenium, Silicon, Arsenic, Boron, Vanadium, Nickel, Cadmium, Lithium, Lead and Molybdenum. Minerals explained in my presentation are: 1) Zinc 2) Selenium 3) Copper and 4) Boron.
  • 4. 1. ZINC Overview: • 30th element in the periodic table (IIB element) – MW = 65.37, completely filled d orbitals • In aqueous solutions – One oxidation state, namely Zn2+ – Prefers tetrahedral complex formation • Not a redox active metal – readily complexes with amino acids, peptides, proteins and nucleotides – affinity for thiols, hydroxy groups & ligands with electron-rich nitrogen donors • Approximately 300 enzymes are associated with zinc • Biological functions of Zn are divided into three categories – Catalytic, Structural, Regulatory
  • 5. FUNCTIONS OF ZINC 1.) Zinc-containing enzymes : serving as an essential cofactor •More than 70 enzymes •Secondary & tertiary protein structures •Metal stabilized active sites •Examples of general types of enzymes requiring Zn as cofactor: Dehydrogenases Anhydrase Polymerases dismutases phosphatases peptidases kinases deaminases
  • 6. 2. Zn: Nuclear transcription factors (>130) •Same protein structural role forms “zinc-fingers” •“Zn-fingers” bind DNA •allow different nuclear hormones to interact with DNA via different DNA binding proteins •up to 37 “fingers” have been found on a single transcription factor •Vit. A, Vit. D, steroid hormones, insulin-like growth factor-1, growth hormone, and others bind to zinc-finger proteins to modulate gene expression. •Zn is responsible for thymidine incorporation 3. Cu/Zn Superoxide Dismutase General class of enzymes that protect against oxidative damage in the body. 4. Insulin Zn important structurally Zn needed for insulin “stored” in pancreas Functionality drops rapidly so more of a “working store” than a static store
  • 7. Transcription Factors • Transcription factors – Regulate gene expression – Involved in virtually all biological processes: • Development, differentiation, cell proliferation, response to external stimuli – Consists of 2 domains • DNA Binding Domain (DBD) – recognizes and binds to specific DNA sequence elements in the promoter of target genes • Protein-interacting Trans activation Domain (TAD) – influences the rate of transcription. • Revelation – Gene expression is controlled by specific proteins call transcription factors • Zinc containing transcription factors account for 1% of genome – Zinc plays key structural role in transcription factor proteins – Ligands for transcription factors include: • Vitamin A • Vitamin D • Bile acids • Thyroid hormones
  • 8. Zinc Finger Proteins • Zinc finger proteins are characterized by their utilization of zinc ions as structural components • C2H2 zinc finger binding motif – Predominant motif in eukaryotic transcription – Involved in skeletal differentiation – Zinc binding motif is determined by the Zinc-finger presence of 2 cysteine and 2 histidine Interacting with DNA residues that engage in a four coordinate bond with a singe Zn ion – Bind to response elements in the upstream promoters of genes transcribed by RNA poly 2 – Binds to 5S ribosomal RNA gene, and 5S RNA, and activates transcription by RNA polymerase 3.
  • 9. Membrane Stability • Membrane fractions contain high concentrations of Zn – Increases rigidity of cell • Protection from oxidative damage – Competition for binding sites with redox metals Membrane Function In deficient animals: – Failure of platelet aggregation • Due to impaired Calcium uptake – Peripheral neuropathy • Brain synaptic vesicles exhibit impaired calcium uptake – Increased osmotic fragility in RBCs • Decreased plasma membrane sulfhydryl concentration Immune Function • After Zinc depletion – All functions within monocytes were impaired – Cytotoxicity decreased in Natural Killer Cells – Phagocytosis is reduced in neutrophils – Normal function of T-cells are impaired – B cells undergo apoptosis • High Zn supplementation shows alterations in cells similar to Zn depletion
  • 10. Whole Body Fluxes Plasma/Serum 2.4 mg Target tissues Diet Zn++ a-2 macroglobulin Including 4-15 mg/da (30%) Liver (~0.15 mM) albumin 1.2 g (60%) Intestine Zn++ (50-100mM) Milk: 2-3 ug/mL 1-2 mg/da Pancreatic & Metallothionine Biliary Other Losses: Excretion: Sweat, Skin, Hair up to Chelating Agents 1 mg/da Phytates 4-5 mg/da Seminal Fluid: 196 ug/mL Menstrual Loss: 0.1-0.5 mg Feces: 3-14 mg/da Urine: 0.4-0.6 mg/da
  • 11. Absorption • Absorption takes place throughout the intestine – Primarily in the jejunum – Some absorption in the rumen – No measurable amounts absorbed from stomach cecum or colon • In small intestine – Nonmediated (nonsaturable) process • Not affected by dietary Zn intake – Mediated (saturable) process • Stimulated by Zn depletion
  • 12. Absorption Mucosa Serosa NSBP CRIP Zn++-Albumin Zn++ Zn++ Saturable = Bound to CRIP-Zn Albumin form transport MTI-Zn ligand Zn++-Albumin MTI Zn++ Zn++ Non-saturable = Passive Diffusion CRIP=cysteine-rich intestinal protein; MTI=metallothionine; NSBP, non-specfic binding protein
  • 13. Dietary Factors that Affect Zn Absorption • Feed/Food source • Presence/Absence of other divalent cations • Phytate (calcium-phytate-zinc – Fe, Ca complex) • Efficiency of absorption can vary – Mainly hexa- and from 15-60% pentaphosphate derivatives – Under normal conditions 1/3 of – Highly dependent on calcium dietary Zn is absorbed – Zn status alters efficiency of • Amino Acids absorption – histidine, cysteine • Uptake and retention is > in growing animals
  • 14. Transport in blood • Plasma contains approx .1% of the total zinc of the body • Albumin is major portal carrier • Binds to albumin by tetrahedral ligation to sulfur atoms – 70% of Zn is bound to albumin in plasma – 20-30% bound to α-2 macroglobulin – Other plasma proteins • Transferrin, histidine-rich glycoprotein, metallothionine • Plasma Zn concn’s respond to external stimuli – Intake fluctuations – Fasting – Acute stresses • infection • Plasma Zn levels do not influence absorption from mucosa • Most reductions in plasma levels reflect increased hepatic uptake – Hormonal control
  • 15. Excretion • Lost via hair, sweat, desquamation, bile pancreatic secretions, seminal fluid, urine, feces • Main endogenous loss – Secretions into gut • Bile and pancreas – Mucosal cells • Urinary and integumental losses • < 20% under normal conditions – Losses increase with trauma, muscle catabolism, and administration of chelating agents (EDTA) • Primarily in fecal material – Unabsorbed Zn – Secreted Zn (endogenous sources) • From pancreatic and intestinal
  • 16. Regulation • Metallothionein – Concentrated in liver, kidney, pancreas, intestine – Acts as a Zn2+ buffer • Controls free Zn2+ level • Control intracellular Zn pool responsive to both hormones and diet • Zn-binding protein, metallothionein (MT), is involved in the regulation of Zn metabolism • MT is inducible by dietary Zn via the metal response element (MRE) and MTF-1 mechanism of transcriptional regulation – ↑ in cellular MT  ↑ Zn binding within cells • Acute infections associated with proinflammatory cytokines increses Zn uptake into liver, bone marrow and thymus and reduces the amount going to bone, skin and intestine
  • 17. Storage • Storage sites – No specfic storage sites are recognized • Within cells, amounts sequestered within metallothionine could be considered as stores • Anorexia, muscle catabolism, tissue zinc release – Metalloenzymes cling tenaciously to zinc – Serum/plasma zinc drops rapidly (~1 week) with zinc deficient diet • Zinc turnover is extensive and rapid – Two-components of turnover, fast ~12.3 days, and slow, ~300 days • Fast pool is also called the “exchangeable” pool – Usually amounts to 157-183 mg Zn
  • 18. Interactions • Copper: - High Zn diets reduce Cu absorption • electronic configuration competition – Metallothionine synthesis induced • sequesters Cu in mucosal cell preventing serosal transfer – Happens with 150mg Zn for two years – Can be used with Wilson’s disease patients – High copper diets do not interfere with Zinc absorption • Iron: Supplements inhibit zinc absorption • Ferrous > Ferric, heme no effect • Pregnant and taking >60mg Fe/day should also take Zn • Calcium: High Ca diets reduce Zn absorption • effect enhanced in phytate rich diets • not sure how much of a problem in humans – post menopausal women yes, adolescent girls, no • Other: – Tin (Sb), not usually high in diet, but diets high in Tin can increase fecal Zn excretion – Cadmium (Cd), alter Zn distribution in body rather than altering absorption – Folic acid, conjugase requires Zn • High doses sometimes impair Zn status further in low Zn situation - mechanism currently unclear
  • 19. Mechanisms of Toxicity • Excess accumulation within cells may disrupt functions of biological molecules – Protein, enzymes, DNA • Leads to toxic consequences • Anemia – Impaired copper availability • Acute excessive intakes – Local irritant to tissues and membranes • GI distress, nausea, vomiting, abdominal cramps, diarrhea • Relatively non-toxic – Sources of exposure – drinking water, feed, polluted air
  • 20. Deficiency • Signs • More signs – Growth retardation – Night blindness – Delayed sexual maturation & impotence – Impaired taste (hypoguesia) • Impaired testicular development – Delayed healing of wounds, burns, – Hypogonadism & hypospermia decubitus ulcers – Alopecia – Impaired appetite & food intake – Acroorifical skin lesions – Eye lesions including photophobia • Other, glossitis, alopecia & nail & lack of dark adaptation dystrophy – Immune deficiencies – Behavioral changes
  • 21. Sources • Relatively abundant mineral – Good sources: shellfish, beef and other red meats – Slightly less good: Whole-grains – most in bran and germ portions • 80% lost to milling • phytates, hexa & penta phosphates depress absorption – P/Zn ratios of 10 or more – Relatively good sources: nuts and legumes • Eggs, milk, poultry & fish diets lower than pork, beef, lamb diets – High meat diets enhance absorption • 280g or 10 oz fits right into food pyramid guide • cys & met form stable chelate complexes
  • 22. 2010 RDA Adult: Children Men: 12mg/day 1-3 yrs: 5 mg/day Women: 11mg/day 4-6 yrs: 7 mg/day 7-9 yrs:8mg/day Pregnancy and lactation : 12mg/day Boys: 10-12 yrs: 9mg/day 13-15 yrs:11mg/day 16-17 yrs:12mg/day Girls :10-12 yrs:9mg/day 13-15 yr:11mg/day 16-17 yrs:12mg/day
  • 23. 2. SELENIUM •Selenium as a metal was first reported by Berzelius in 1817 and occur in nature in variety of forms and colours. •Selenium is frequently found in combination with lead, copper, mercury and silver. These combinations are called selenides. •Selenium is an allotropic metal in group 6 of the fourth period of the periodic table. Its molecular weight is 78.96 Da and its atomic weight is 34. •Selenium has 26 isotopic forms, only 5 of these are naturally occuring: Se76,Se78,Se77,Se80,Se82.Of the radioisotopes. •Se and Vit.E both play important roles in the detoxification of peroxide and free radicals.
  • 24. FUNCTIONS OF SELENIUM: 1. Component of glutathione peroxidase • catalyzes removal of hydrogen peroxide GSH + H2O2 GSSG + H2O GSH = reduced glutathione GSSG = oxidized glutathione 2. Component of iodothyronine-5’- deiodinase • Converts T4 to T3 3. Improves killing ability of neutrophils • Reduces the prevalence and severity of mastitis 4.Protects cells from auto oxidative damage Shares this role with vitamin E 5.) Important antioxidant
  • 25. Relationship of glutathione peroxidase,selenium, and vitamin E GSH peroxidase contains selenocysteine
  • 26. Selenoproteins: Enzyme Activities 1. At least 25 selenoproteins have been identified in human biochemistry. 2. Glutathione peroxidase (GPx) has been the functional parameter used for the assessment of Se status. GPxs catalyze the reduction of peroxides that can cause cellular damage. 3. Thioredoxin reductase (Trx R) provides reducing power for several biochemical processes and defends against oxidative stress. 4. Selenoprotein P, the majority of the Se found in the bloodstream, acts as an antioxidant enzyme. 5. Selenoprotein W may play a role in oxidant defense. 6. The peroxiredoxins (Trx PX) define an emerging family of peroxidases able to reduce hydrogen peroxide and alkyl hydroperoxides. 7. Selenophosphate synthetase is an enzyme required for the incorporation of selenocysteine into selenoproteins.
  • 27. ABSORPTION, METABOLISM AND EXCRETION Absorption is very efficient , with most of the ingested selenium absorbed readily from a variety of food stuffs. The source of the mineral can have effects on its absorption. Se is transported from the gut on the VLDL and LDL : Red cells, liver, spleen, muscles, nails, hair and tooth enamel all contain significant quantities of the mineral. DAILY SELINIUM FLUX IN A 70 KG MAN Sweat, skin loss ~ 80 μ g/day Diet 6- Plasma VLDL,or LDL, 0.5-2.0g/ml Feces ~ 50 200μg/day μ g/day (50-200 μ g/L) Urine~ 50 μ g/day Selenoproteins in tissues
  • 28. Food Sources Food content tends to follow Se content of soil – richest food sources are organ meats and sea foods, followed by cereals and grains, dairy products, fruits and vegetables Se content of grains can vary by 10,000 fold • Requirements determined based on serum glutathione peroxidase activity. • The NAS-NRC has recommended that an intake no less than 50 and no mare than 200g/day should be sufficient to meet need of average adult. Selenium Deficiency Diseases • Major problem in livestock • Human deficiency is rare except in areas with low Se content in soil Keshan disease occurs in Keshan China: endemic cardiomyopathy and muscle weakness (due to oxidized lipids) Aggressive supplementation has eliminated disease • Iatrogenic deficiency TPN without supplemental Se
  • 29. Selenium Toxicity • Range of dietary Se intake without toxicity is narrow • Acute selenium poisoning can result in cardiorespiratory collapse • Chronic toxicity (selenosis) changes in nail structure and loss of hair • Hair and nail brittleness • Se toxicity in farm animals is characterized by Hoof loss and a neuromascular condition known as “Blind Staggers”.
  • 30. Selenium and Cancer Prevention • Epidemiologic evidence indicates low intakes of Se are associated with higher risk of prostate cancer • Prospective study of Se supplementation demonstrated 42% reduction in cancer incidence • Small sample size and other confounding factors have diminished enthusiasm for the results of these studies. • In 1977, Gerhard Schrauzer and his team reported that Se is a potential human cancer-protective agent. • Later human epidemiological studies indicate a statistically significant inverse relationship between Se level and risk of cancer overall, particularly in men. Moreover, clinical trials showed that supplemental Se reduced the incidence and mortality of several types of human cancers. • In the 1980s, the birth of synthetic organoselenium derivatives as cancer chemopreventive agents in laboratory rodents was reported by Karam El- Bayoumy. • Currently two clinical invention trials in the U.S. (Selenium and Vitamin E Cancer Prevention Trial, SELECT), Phase III, and in Europe (Prevention of Cancers by Intervention with Selenium, PRECISE) are in progress.
  • 31. 3. BORON •Boron is the chemical element with atomic number 5 and the chemical symbol B. Because boron is produced entirely by cosmic ray spallation and not by stellar nucleosynthesis,[6] it is a low-abundance element in both the solar system and the Earth's crust. However, boron is concentrated on Earth by the water-solubility of its more common naturally occurring compounds, the borate minerals. These are mined industrially as evaporate ores, such as borax and kernite. •Boron was shown to be an essential element for plants early this century and there is now evidence that it is also necessary for humans. Boron is distributed throughout the human body with the highest concentration in the bones and dental enamel. •Prior to 1981, boron was not considered an essential nutrient; boron was first shown to be an essential mineral for growing chicks. It was not until 1990 that boron was accepted as an essential nutrient for humans.
  • 32. FUNCTIONS OF BORON: • Boron seems to be essential for healthy bone and joint function, possibly via effects on the balance and absorption of calcium, magnesium and phosphorus. It seems to affect cell membranes and the way signals are transmitted across these membranes. • Boron affects the metabolism of steroid hormones and may also play a role in converting vitamin D to its more active form, thus increasing calcium uptake and deposition into bone. Boron also increases male sex hormone levels. • Boron is required for the maintenance of bone and normal blood levels of estrogen and testosterone; within eight days of supplementing boron women lost 40 percent less calcium, 33 percent less magnesium and less phosphorus through their urine. 1. Through reactions with certain bio substances to maintain proper cell membrane function or stability and influences hormone reception and transmembrane signaling.
  • 33. Absorption and metabolism Boron is efficiently absorbed and excreted in the urine. Deficiency •Boron deficiency seems to affect calcium and magnesium metabolism, and affects the composition, structure and strength of bone, leading to changes similar to those seen in osteoporosis. •This is likely to be due to decreased absorption and increased excretion of calcium and magnesium. •Boron deficiency combined with magnesium deficiency appears especially damaging in cases of osteoporosis. Due to its effects on calcium and magnesium metabolism, boron deficiency may also contribute to the formation of kidney stones. Boron deficiency also seems to decrease mental alertness. •There may also be a link between boron deficiency and osteoarthritis.
  • 34. Dietary need and sources Human requirement of Boron most likely between 0.5 and 1.0 mg/day; rich food sources include noncitrus fruits, leafy vegetables, nuts, pulses and legumes. Boron toxicology Toxic effects appear at intakes of about 100 mg. The World Health Organization has banned boron (in the form of boric acid) as a food additive and preservative. Toxic effects include a red rash with weeping skin, vomiting, diarrhea characterized by a blue green color, depressed blood circulation, coma and convulsions. A fatal dose in adults is 15 to 20 g and in children 3 to 6 g. Repeated intakes of small amounts can cause accumulative toxicity. Signs of toxicity include nausea, vomiting, diarrhea, dermatitis, and lethargy. In addition, excess boron intake induces riboflavinuria. Landauer found that boron-induced teratogenic problems include skeletal abnormalities and were reduced with riboflavin therapy.
  • 35. Supplements Sodium borate is the most common form of supplement. Boron is increasingly used in calcium and bone- replenishing nutritional formulas. It may be particularly useful in those whose magnesium intake is low. This effect may be useful in the prevention of kidney stones. Because of its effect on testosterone levels, boron supplements have been marketed to athletes on the basis of their ability to increase muscle mass and strength. A 1994 study of the effects on ten male bodybuilders did not find any increases in those with boron supplements.
  • 36. Therapeutic uses of supplements Boron may be beneficial in the treatment of osteoporosis. Supplements of around 3 mg per day have been shown to enhance the effects of estrogen in postmenopausal women. This is likely to contribute to its beneficial effects on bone health. Studies done in 1994 on athletic college women suggest that boron supplements decrease blood phosphorus concentration and increase magnesium concentration. Both of these changes are beneficial to bone-building.Because of its sex hormone-enhancing effects, boron may help to protect against atherosclerosis. Osteoarthritis Boron supplements of 6 to 9 mg per day have been used to treat osteoarthritis with some improvement of symptoms. Boron content in arthritic bones may be lower than that of normal bones and extra boron may increase bone hardness.
  • 37. Interactions with other nutrients •boron is an essential element and that it is involved in regulating parathormone action. Therefore, it is likely that boron influences the metabolism of calcium, phosphorus, magnesium and cholecalciferol. •Animal studies have indicated that cholecalciferol deficiency enhances the need for boron, and that boron might interact in some manner other than through an effect on cholecalciferol metabolism. •The relationship seemed strongest between boron and magnesium, because boron supplementation alleviated magnesium deficiency signs in chicks. Boron does not seem to consistently alleviate signs of calcium and phosphorus deficiency. •Boron and boron compounds can influence calcium metabolism, and tissue boron level changes in animals with abnormal calcium metabolism. In humans, a low caries incidence has been associated with adequate boron levels; however other studies indicated that high levels of orally administered boron increased dental caries.
  • 38. 4. COBALT: Cobalt is another essential mineral needed in very small amounts in the diet. It is an integral part of part of vitamin B12, cobalamin, which supports red blood cell production and the formation of myelin nerve coverings. Some authorities do not consider cobalt to be essential as a separate nutrient, since it is needed primarily as part of B12, which is itself essential.Cobalt, as part of vitamin B12, is not easily absorbed from the digestive tract. The body level of cobalt normally measures 80-300 mcg. It is stored in the red blood cells and the plasma, as well as in the liver, kidney, spleen, and pancreas . Sources: Cobalt is available mainly as part of B12. There is some question as to whether inorganic cobalt is actually usable in the human body. Meat, liver, kidney, clams, oysters, and milk all contain some cobalt. Ocean fish and sea vegetables have cobalt, but land vegetables have very little; some cobalt is available in legumes, spinach, cabbage, lettuce, beet greens, and figs.
  • 39. Functions: As part of vitamin B12, cobalt is essential to red blood cell formation and is also helpful to other cells. Uses: Cobalt, as part of B12, is used to prevent anemia, particularly pernicious anemia; vitamin B12 is also beneficial in some cases of fatigue, digestive disorders, and neuro-muscular problems. There are no other known uses except for the radioactive cobalt-60 used to treat certain cancers. Deficiency and toxicity: Toxicity can occur from excess inorganic cobalt found as a food contaminant. Beer drinker's cardiomyopathy (enlarged heart) and congestive heart failure have been traced to cobalt introduced into beer during manufacturing. Increased intake may affect the thyroid or cause overproduction of red blood cells, thickened blood, and increased activity in the bone marrow.
  • 40. . Requirements: No specific RDA is suggested for cobalt. Our needs are low, and vitamin B12 usually fulfills them. The average daily intake of cobalt is about 5-8 mcg. It is not usually given in supplements. Absorption and bioavailability: The extent of gastrointestinal absorption of cobalt depends upon the dose, with very low doses being almost completely absorbed, whereas larger doses are less well absorbed. Nutritional factors also influence absorption, for example, absorption is reduced by amino acids, and increased in iron deficiency. Distribution and metabolism: In human autopsy studies, the liver (the organ where vitamin B12 is stored) contains the highest concentration of cobalt (approximately 20% of the total body content). In the human body there is no evidence of accumulation of cobalt with age. Excretion: Cobalt is mainly excreted in the urine but also in the faeces. Independent of the route of exposure, most cobalt is eliminated rapidly, with a small proportion being eliminated slowly and having a half-life of the order of years.
  • 41. studies related to cobalt: Human data Seghizzi et al., 1994 A review of the literature from the 1960s described endemics of cardiomyopathy with mortality rates of up to 50 % in heavy consumers of cobalt-fortified beer (containing cobalt concentrations of 1 – 1.5 ppm). The intake of cobalt in such consumers was estimated to be 6 – 8 mg daily. Dietary protein deficiency may be an important factor in cobalt induced cardiomyopathy, and zinc and magnesium deficiency may also play a part. Animal data Pedigo et al., 1988 Cobalt chloride was administered to groups of 10 mice in drinking water providing 23, 42 or 72 mg cobalt/kg bw/day for up to 13 weeks. The highest dose level resulted in a dose- and time-dependent decrease in testicular weight and decreased epididymal sperm concentration, along with decreases in both motility and percent motile forms of sperm. Fertility was decreased at week 13. There was a dosedependent decrease in testicular weights (as a ratio to body weight), whilst serum testosterone levels were increased 5 to 7 fold at all dose levels.
  • 42. REFERENCES: 1. Berdanier .C.D., Advanced Nutrition Micronutrients. CRC Press. 2. Shils et al., Modern Nutrition in the health and Disease. Lippincott Williams & wilkins, New York. 2006. 3. Stump et al., Krause’s Food & Nutrition Therapy. Saunders Elsevier. International edition. 2008. 4. Guthrie., Introductory Nutrition .The C.V. Mosby Company.5th edition , 1983. 5. Stipanuk.H.Martha., Biochemical and Physiological aspects of Human Nutrition, Saunders Elsevier.2000. 6. http://www.dcnutrition.com/minerals/detail.cfm?RecordNumber=47 7. http://jctonic.com/include/minerals/boron.htm 8. http://www.fasebj.org/content/1/5/394.short 9. http://en.wikipedia.org/wiki/Boron 10. http://www.healthy.net/scr/article.aspx?Id=2051 11.http://www.food.gov.uk/multimedia/pdfs/evm_cobalt.pdf 12.http://en.wikipedia.org/wiki/Cobalt.

Editor's Notes

  1. Redox metal catalyze oxidation
  2. Glycocalyx – mucus layer
  3. Metallothionein proteins participate in the uptake, transport, and regulation of zinc in a biological system. The zinc binding sites are typically cysteine-rich, and often bind three or four zinc ions. In some proteins, histidine also participates in zinc binding. By binding and releasing zinc, metallothioneins (MTs) regulate its level within the body. Zinc, in turn, is a key element for the activation and binding of certain transcription factors through its participation in (aptly-named) zinc fingers . Metallothionein also carries zinc ions (signals) from one part of the cell to another. When zinc enters a cell, it can be picked up by thionein (which thus becomes &quot;metallothionein&quot;) and carried to another part of the cell where it is released to another organelle or protein. In this way the thionein-metallothionein becomes a key component of the zinc signaling system in cells. This system is particularly important in the brain, where zinc signaling is prominent both between and within nerve cells. It also seems to be important for the regulation of the tumor suppressor protein p53. Metallothionein (MT) detoxifies mercury and heavy metals by binding to the metal before it can cause harm. It forms subcellular inclusions or crystals which act jointly to consolidate and enclose excess metals. These inclusions then accumulate within tissues or skeletal structure over time. Low Zn  bind to CRIP, High Zn  bind to MT.
  4. Alpha-2 macroglobulin is a large plasma protein found in the blood . It is produced by the liver , and is a major component of the alpha-2 band in protein electrophoresis .
  5. Metallothioneins are proteins whose purpose is to metabolise and regulate metals . Their production is dependent on availability of the dietary minerals zinc and selenium , and the amino acids histidine and cysteine .
  6. Some metalloenzymes include hemoglobins, cytochromes, phosphotransferases, alcohol dehydrogenase, arginase, ferredoxin, and cytochrome oxidase. Carboxypeptidase A is a zinc metalloenzyme that breaks peptide linkages in the digestion of proteins. The zinc ion that the enzyme contains in its active site plays a key role in that function.