Minerals

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Minerals

• By
• Henry Wormser, Ph.D.

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Minerals

• minerals are elements of the periodic table
• more than 25 have been isolated
• 21 elements have been shown to be essential
  (excluding C,H, and O)
• minerals make up about 4 to 5 of body weight
  (for a 70 kg individual 2.8 kg)
• many minerals are found in ionic form (others as
  ligands or covalent compounds)

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Minerals

• Two categories
• macrominerals gt 0.005
• microminerals lt 0.005
• macrominerals are essential at levels of 100mg or
  more per day for human adults
• microminerals are often referred to as trace
  elements

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Macrominerals

• Ca calcium 1200 grams
• P phosphorus 860 grams
• S sulfur 300 grams
• K potassium 180 grams
• Cl chloride 74 grams
• Na sodium 64 grams
• Mg magnesium 25 grams

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Microminerals

• F fluorine 2.6 V vanadium 0.018
• Zn zinc 2.0 Sn tin 0.017
• Cu copper 0.1 Se selenium 0.013
• I iodine 0.025 Mn manganese 0.012
• Cr chromium 0.006 Ni nickel 0.010
• Co cobalt 0.0015Mo molybdenum 0.009
• Si silicon 0.024

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Other microminerals found in humans

• Sr (strontium)
• Br (bromine)
• Au (gold)
• Ag (silver)
• Al (aluminum)
• Bi (bismuth)
• As (arsenic)
• B (boron)
• the function of these minerals has not been
  established as of to date

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Scientific development which have contributed to
trace element knowledge

• design of highly purified and specially
  constituted diets
• advances in analytical measurements
• colorimetruy
• fluorimetry
• flame photometry
• neutron activation analysis
• atomic absoption spectroscopy
• microwave excitation emission spectroscopy
• isolation and study of metalloenzymes

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Functions of minerals

• provide a suitable medium for cellular activity
• permeability of membranes
• irritability of muscles and nerve cells
• play a primary role in osmotic phenomenon
• involved in acid base-balance
• confer rigidity and hardness to certain tissues
  (bones and teeth)
• become part of specialized compounds

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Metalloenzymes

• metal is firmly bound
• metal to protein ratio is constant
• metal to enzyme activity ratio is constant
• metal is unique
• no enzyme activity without metal

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Metalloenzymes

• Examples of metalloenzymes
• superoxide dismutase (Zn and Cu)
• carboxypeptidase A (Zn)
• carbonic anhydrase (Zn)
• cytochrome oxidase (Fe and Cu)
• xanthine oxidase (Co and Fe)

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Metal-activated enzymes

• metal is reversibly bound
• metal to protein ratio is variable
• metal to enzyme activity ratio is variable
• metal is not necessarily unique
• enzyme activity may exit without metal

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Metal-activated ezymes

• Examples of metal-activated enzymes
• creatine kinase (Mg, Mn, Ca or Co)
• glycogen phosphorylase kinase (Ca)
• salivary and pancreatic alpha-amylases (Ca)

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The electrolytes

• There are 3 major electrolytes
• sodium
• potassium
• chloride

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Sodium (Na)

• Sodium is the principal cation in extracellular
  fluids
• functions include
• osmotic equilibrium
• acid-base balance
• carbon dioxide transport
• cell membrane permeability
• muscle irritability

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Sodium (Na)

• food sources table salt, salty foods (potato
  chips, pretzels, etc.), baking soda, milk
• absorption and metabolism
• readily absorbed
• excreted in the urine and sweat
• aldosterone increases reabsorption in remal
  tubules

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Sodium (Na)

• RDA for adults 1.1 to 3.3 gm/day
• sodium deficiency
• dehydration
• acidosis
• tissue atrophy
• sodium excess
• edema (hypertonic expansion
• hypertension

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Sodium (Na)

• Sodium supplements
• usually used to replace sodium and chloride lost
  through perspiration during high heat
• Thermotabs
• Slo-salt
• Heatrol
• Lytren solution
• Pedialyte solution
• Gatorade and other sports drinks

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Potassium (K)

• Potassium is the principal cation in
  intracellular fluid
• functions
• buffer constituent
• acid-base balance
• water balance
• membrane transport
• neuromuscular irritability

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Potassium

• Food sources vegetables, fruit (bananas), whole
  grains, meat, milk
• absorption and metabolism
• readily absorbed (more so than sodium)
• intracellular
• secreted by kidney (also in sweat)
• RDA for adults 1.5 - 4.5 gm/day

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Potassium

• deficiency (hypokalemia)
• causes
• increased renal excretion (diuretics)
• primary aldosteronism
• severe vomiting and diarrhea
• cutaneous losses via perspiration
• symptoms
• profound weakness of skeletal muscles (paralysis
  and impaired respiration
• weakness of smooth muscles
• cardiac anomalies AV block, cardiac arrest

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Potassium

• excess (hyperkalemia)
• causes
• sudden increased intake
• severe tissue trauma and burns
• acute and chronic acidosis
• symptoms
• weakness and paralysis
• cardiac anomalies (impaired conduction,
  fibrillations, cardiac arrest)

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Potassium supplements

• Oral products
• tablets potassium chloride, potassium
  gluconate, Slow-K
• effervescent tablets K-Lyte, K-Lor, Kaochlor
• parenteral products usually administered by slow
  IV infusion (KCl and K acetate)

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Treatment of hyperkalemia

• reverse cardiotoxic effects
• calcium gluconate IV
• increase potassium uptake by cells
• dextrose (IV)
• insulin (IV)
• sodium bicarbonate (IV)
• remove excess potassium from the body
• sodium polystyrene sulfonate (Kayexalate)

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Chloride (Cl)

• an essential anion
• closely connected with sodium in foods, body
  tissues and fluids and excretions
• readily absorbed along with sodium
• excreted mainly in the kidneys ( 2 in feces and
  4-5 in perspiration
• important for osmotic balance, acid-base balance
  and in the formation of gastric HCl

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Chloride (Cl)

• Deficiency of chloride
• hypochloremic alkalosis
• hypovolemia
• pernicious vomiting
• psychomotor disturbances

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Calcium (Ca)

• the most abundant of the minerals
• the 5th most abundant element in the body
• needed by all cells
• found in largest amounts in bones (90)
• found in bone as hydroxyapatite Ca10(PO4)6(OH)2
• contaminated with sodium, potassium, magnesium,
  carbonate and fluoride

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Calcium (Ca)

• controlled by parathyroid hormone (PTH),
  calcitonin and vitamin D
• maintained at a concentration of 5 mEq/L in
  plasma
• about 1/2 is in the ionized form in serum
• the other 1/2 is bound to protein (calcium
  citrate complex)

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Calcium (Ca)

• function of calcium
• structural unit of bones and teeth
• contraction and relaxation of muscles
• stabilizes nervous tissue
• low calcium --- irritable nerves --- tetany
• high calcium --- depresses the nervous
  irritability
• required for blood clotting
• activates various enzymes (glycogen phosphorylase
  kinase, salivary and pancreatic amylase)

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Calcium (Ca)

• Calcium absorption
• variable due to insoluble salts
• phosphate
• carbonate
• oxalate
• phytate
• sulfate
• also forms calcium soaps with fatty acids
• absorption is enhanced by
• acid pH
• vitamin D
• lactose
• lysine and glycine

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Calcium (Ca)

• Excretion
• urine and feces
• enhanced by lack of vitamin D and ingestion of
  large quantities of proteins (acid urine)
• RDA
• adult 800 mg/day
• pregnacy and lactation 1200 mg/day

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Calcium supplements

• calcium gluconate 9
• calcium lactate 13
• calcium carbonate 40
• dibasic calcium phosphate 30
• calcium glucobionate 6
• calcium chloride 27.2
• calcium levulinate 13

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Phosphorus

• required in many phases of metabolism
• food sources
• phosphoproteins
• nucleoproteins
• nucleolipids
• glycerophosphates
• inorganic phosphates (Na and Ca)
• foods rich in calcium are also richest in
  phosphorus (milk, cheese, eggs, beans, fish)

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Phosphorus

• Phosphorus is the second most abundant mineral in
  the body (22 of total mineral content 80 is
  structural insoluble apatite in bone and teeth)
• 20 is very active metabolically
• High energy phosphate compounds
• Nucleic acids
• Phospholipids
• Phosphoproteins
• Coenzymes (vitamins)

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Phosphorus

• RDA for phosphorus is established on the basis of
  a 11 relationship with calcium
• Adults 800 mg/day
• Pregnancy and lactation 1200 mg/day
• Phosphorus deficiency (hypophosphatemia)
• Not common
• May be associated with total parenteral nutrition
  (TPN) without sufficient phosphates give either
  sodium or potassium phosphate

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Magnesium (Mg)

• second most plentiful cation in intracellular
  fluids
• 50 of total amount in bone
• 45 in muscle and nervous tissue
• 5 in extracellular fluids
• blood plasma magnesium 2 mEq/L

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Magnesium (Mg)

• Functions
• a. enzyme systems
• cofactor of all enzymes involved in phosphate
  transfer reactions that use ATP and other
  nucleotide triphosphates
• phosphatases
• pyrophosphatases

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Magnesium (Mg)

• b. CNS
• hypomagnesemia ---- cns irritability,
  disorientation, psychotic behavior, convulsions
• c. neuromuscular system
• magnesium has a direct depressant effect on
  skeletal muscle
• magnesium also causes a decrease in Ach release
  at motor end plate (used in treatment of
  eclamptic seizures)

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Magnesium

• Abnormally low concentrations of Mg in the
  extracellular fluid ---- increased Ach release
  ---- increased muscle excitability (tetany)
• food sources all green plants (chlorophyll)
  meats
• RDA 350 mg/day
• pregnancy and lactation 450 mg

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Magnesium products
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Zinc

• Biological roles
• Involved in many enzymes (over 20 metalloenzymes)
• Carbonic anhydrase
• Carboxypeptidase A
• Four types of proteases
• Serine
• Cysteine
• Aspartic acid
• Zinc
• ACE (angiotensin I convering enzyme)
• RNA and DNA polymerases

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Zinc

• zinc absorption appears to be dependent on a
  transport protein, metallothionein
• deficiencies include poor growth, delayed wound
  healing, impairment of sexual development and
  decreased taste acuity
• zinc is present in gustin, a salivary polypeptide
  that is necessary for the development of taste
  buds

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Zinc

• severe zinc deficiency is seen primarily in
  alcoholics (especially if they have developed
  cirrhosis), patients with chronic renal disease
  or severe malabsorption diseases
• occasionally seen in patients on long term total
  parenteral nutrition (TPN) patient develop a
  dermatitis
• zinc is occasionally used therapeutically to
  promote wound healing and may be of some use in
  treating gastric ulcers

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Zinc supplements
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Iron (Fe)

• 2 types of body iron
• heme iron
• hemoglobin, myoglobin, catalases, peroxidases,
  cytochromes (a, b and c involved in electron
  transport), cytochrome P450 (involved in drug
  metabolism)
• non-heme iron
• ferritin, hemosiderin, hemofuscin, transferrin,
  ferroflavoproteins, aromatic amino acid
  hydroxylases
• food iron is also classified as heme and non-heme

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Food iron

• heme iron
• meats
• poultry
• fish
• 20-23 of heme-iron is absorbable

• non-heme iron
• vegetables
• fruits
• legumes
• nuts
• breads and cereals
• only 3 on non heme iron is absorbed

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Iron absorption

• occurs in upper part of small intestine
• about 10 of food iron is absorbed
• requires gastric HCl (releases ionic iron)
• also requires copper
• ferrous is better absorbed than ferric form
• Fe forms chelates with ascobic acid, certain
  sugars and amino acid

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Iron distribution and storage

• carried in blood stream via transferrin (a b
  globulin)
• stored in 2 forms
• ferritin (a water soluble complex consisting of a
  core of ferric hydroxide and a protein shell
  (apoferritin)
• hemosiderin (a particulate substance consisting
  of aggregates of ferric core crystals)
• stored in liver, spleen, bone marrow, intestinal
  mucosal cells and plasma

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Iron elimination

• there is no mechanism for excretion of iron
• iron is normally lost by exfoliation of
  intestinal mucosal cells into the stools
• trace amounts are lost in bile, urine and sweat
  (no more than 1 mg per day)
• bleeding (vaginal, intestinal) is a more serious
  mechanism of elimination

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IRON DEFICIENCY

• Initial symptoms are vague and ill-defined
• easy fatigability
• lack of appetite
• headache
• dizziness
• palpitations
• then hypochromic-microcytic anemia
• microcytosis (small RBCs)
• hypochromia (poor fill of hemoglobin)
• poikilocytosis (bizarre shapes)
• anisocytosis (variable sizes)

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IRON DEFICIENCY

• Causes
• excessive blood loss (parasitic, accidental,
  menstrual) is most common cause
• rapid growth in children with limited intake of
  iron
• malabsorption
• gastric resection
• sprue
• increased metabolic requirement
• pregnancy, lactation or neoplasia

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Diagnosis of iron deficiency

• hematology (microcytic hypochromic cells)
• low serum iron
• low serum ferritin( indicates low body stores)
• in some conditions (inflammation, hepatitis)
  ferritin may be high
• low hemosiderin
• high total iron binding capacity (TIBC)

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Iron absorption

• average diet contains 10 - 15 mg of iron perday
• a normal person absorbs 5 -10 of this iron or
  0.5 - 1.0 mg daily
• iron absorption increases in response to low iron
  stores
• menstruating women 1 - 2 mg per day
• pregnant women 3 - 4 mg per day
• absorption is via active process

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Different types of iron

• Ferrous sulfate 20
• Exsiccated ferrous sulfate
• ferrous gluconate 11.6
• ferrous fumarate 33
• ferrocholinate 12
• polysaccharide-iron complex
• iron dextran (Imferon)

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Treatment of iron deficiency

• give 200 - 400 mg of iron per day
• up to 25 of the iron preparation may be absorbed
• 50 - 100 mg of iron may be utilized in case of
  deficiency
• give on an empty stomach
• enteric coated iron tablet should not be used
  since we want absorption to occur in the stomach
  and proximal duodenum

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Treatment of iron deficiency

• parenteral iron is used in patients who have had
  bowel resections or in cases of inflammatory
  bowel disease
• normally given IM (painful) Z-track minimizes
  tatoo
• oral iron causes black stools, constipation,
  cramping
• do not administer with antacids or metal
  chelators (tetracyclines)

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Acute iron toxicity

• common in small children ingesting large doses
  of soluble iron compounds
• toxicity is usually divided into 4 phases
• 1. 30 - 60 min. following ingestion
• abdominal pain
• nausea and vomiting
• signs of acidosis and cardiovascular collapse may
  be seen

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Acute iron toxicity

• 2. Period of improvement - last about 8 to 16
  hours
• 3. Period of progressive cardiovascular collapse
  (about 24 hrs after ingestion)
• convulsions
• coma
• high mortality
• 4. Gastrointestinal obstruction from scarring of
  stomach and small intestine

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Deferoxamine mesylate (DFOM)
A chelating agent which reacts with ferric ion to
form a 11 chelate known as ferrioxamine Marketed
as Desferal Injection (Ciba) Produced by
Streptomyces pilosus
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Chronic iron toxicity

• causes
• hereditary hemochromatosis
• hemosiderosis
• symptoms
• cirrhosis iron deposition in the liver
• diabetes iron deposit in the pancreas (damage to
  beta cells)
• skin pigmentation
• cardiac failure
• treatment phlebotomy ( 1 unit of blood removes
  about 250 mg of iron

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Copper

• important trace mineral
• element 29 on the periodic table
• component of several enzymes
• ceruloplasmin (an oxidase)
• tyrosinase (production of melanin)
• amine oxidase (metabolism of catecholamines)
• cytochrome C oxidase
• dopamine beta hydroxylase
• copper/zinc superoxide dismutase

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Copper (Cu)

• Deficiency
• decreased iron absorption
• neutropenia and leukopenia
• bone demineralization
• failure of erythropoiesis
• sources
• liver, shellfish, whole grains, cherries,
  legumes, nuts

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Fluorine

• Considered essential because of its beneficial
  effect on tooth enamel
• Benefits include less dental caries, stronger
  bones, reduction in osteoporosis and
  calcification of the aorta
• In large quantities it is deleterious to teeth
  dental fluorosis pitting, chalky, dull white
  patches and mottling of teeth
• 1 to 2 parts per million is adequate for drinking
  water

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Iodine

• iodine is necessary for the formation of thyroid
  hormones (T-4 and T-3)
• deficiency of iodine is manifested by a goiter
  (enlargement of the thyroid gland)
• salt water fish and seaweeds are a good source of
  iodine
• to prevent the development of endemic goiter,
  tablet salt has been spiked with sodium iodide

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Fluorine

• Main sources include drinking water and plants
  (spinach, lettuce, onions)
• Average daily intake 1.5 4.0 mg/day
• Fluoride supplementation is available in both
  oral and topical forms
• Oral mainly sodium fluoride (Pediaflor Drops)
• Topical either sodium or stannous fluoride
  (Fluorigard, Karigel, Fluoral)

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Fluoride products
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Silicon

• essentiality has been established in chicks and
  rats, but not humans
• appears to play an important role in the
  development and maintenance of cartilage
  (chondroitin sulfate, hyaluronic acid, keratin
  sulfate)
• may have a protective role in cardiovascular
  diseases (atherosclerosis)
• found in unrefined grains and beer

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Manganese

• Maganese is an activator of several different
  enzymes
• Phosphoglucomutase
• Isocitric dehydrogenase
• Cholinesterase
• Intestinal peptidase
• Carboxylases
• ATPases
• However, magnesium and cobalt can replace Mn in
  several enzymes

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Manganese

• Essential for sulfomucopolysaccharide
  biosynthesis
• Deficiency leads to
• Weight loss
• Transient dermatitis
• Nausea and vomiting
• Changes in hair color
• Sources blueberries, wheat bran, beet greens,
  lettuce, legumes, fruit
• RDA 2.5 5.0 mg

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Chromium

• Cr III may act as a cofactor for insulin,
  enhancing glucose utilization
• deficiency leads to impaired glucose tolerance
  (glucose tolerance factor)
• sources corn oil, whole-grain cereals, clams,
  drinking water (variable)
• forms a coordination complex with micotinic acid
  and the amino acids glycine, glutamate and
  cysteine
• chromium may have a role in type 2 diabetes
• RDA 0.05 0.2 mg
• frequently available in pharmacies as chromium
  picolinate

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Selenium

• prevents
• muscular dystrophy in lambs, calves and chicks
• liver necrosis in rats and pigs
• exudative diathesis in chicks and turkeys
• multiple necrotic degeneration of heart, liver,
  muscle and kidneys in mice
• appears to function in the metalloenzyme
  glutathione peroxidase, which destroys peroxides
  in the cytosol
• no deficiencies have been seen in humans
• has antioxidant activity (may have relationship
  with vitamin E - sparing action)

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Tin

• produces accelerated growth in deficient rats
• tin is similar to carbon in its tendency to form
  covalent bonds
• may have a role with heme-containing enzymesheme
  oxygenase and cytochrome P-450
• largest quantities are found in kidneys and skin
• human intake 1.5 - 3.5mg/day

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Cobalt

• essentiality exists in some animals for ionic
  cobalt (sheep and cattle)
• in rats administration of cobalt produces a
  polycythemia
• cobalt in necessary in humans in the form of
  vitamin B12
• animals and plants cannot synthesize B12
• daily intake 0.3 mg

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Vanadium

• essentiality established in rats and chicks
• human daily intake has been estimated at 2 mg
• plays a role in lipid metabolism (deficient
  chicks have a high plasma cholesterol and
  triglyceride levels)
• may also function as an oxidation-reduction
  catalyst

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Molybdenum

• Widely found in commonly used foods (cereals,
  vegetables
• Mo is part of flavoproteins, xanthine oxidase,
  aldehyde oxidase

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Sulfur

• Most sulfur in the diet comes in from protein
  sources containing sulfur amino acids such as
  cysteine, cystine and methionine
• Some enters as inorganic sulfur (sulfate,
  sulfide, chondroitin sulfate and certain other
  sulfate esters)
• Sulfur is also present in thiamine, biotin,
  sulfolipids, conjugated bile acids and coenzyme A

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The end