minerals and mining 3

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 – aldo

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)

• Two categories:

• macrominerals > 0.005%

• microminerals < 0.005%

• macrominerals are essential at levels of

100mg or more per day for human adults

• microminerals are often referred to as

trace elements

Other microminerals found in

Scientific development which have contributed to trace element knowledge

• design of highly purified and specially

• neutron activation analysis

• atomic absoption spectroscopy

• microwave excitation emission spectroscopy

• isolation and study of metalloenzymes

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

• 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

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

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)

• carbon dioxide transport

• cell membrane permeability

• muscle irritability

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

Sodium (Na)

• Sodium supplements:

– usually used to replace sodium and chloride

lost through perspiration during high heat

• 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

• 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

• 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)

– parenteral products: usually administered

by slow IV infusion (KCl and K acetate)

– sodium bicarbonate (IV)

• remove excess potassium from the body:

– sodium polystyrene sulfonate (Kayexalate)

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

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 Ca 10 (PO 4 ) 6 (OH) 2

• contaminated with sodium, potassium,

magnesium, carbonate and fluoride

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)

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)

• absorption is enhanced by:

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

– inorganic phosphates (Na and Ca)

• foods rich in calcium are also richest in

phosphorus (milk, cheese, eggs, beans, fish)

• 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)

• RDA for phosphorus is established on the basis

of a 1:1 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

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

Magnesium (Mg)

• Functions:

a enzyme systems

– cofactor of all enzymes involved in

phosphate transfer reactions that use ATP and other nucleotide triphosphates

– phosphatases

– pyrophosphatases

– magnesium also causes a decrease in Ach

release at motor end plate (used in treatment

of eclamptic seizures)

• 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

• ACE (angiotensin I convering enzyme)

• RNA and DNA polymerases

• 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

• 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

Zinc supplements

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

– legumes – nuts

– breads and cereals

only ~ 3% on non heme iron is absorbed

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

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

Fe +++ - transferrin plasma

unabsorbed Fe (fecal excretion)

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

• hypochromia (poor fill of hemoglobin)

• poikilocytosis (bizarre shapes)

• anisocytosis (variable sizes)

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

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)

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

Different types of iron

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

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

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

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

Deferoxamine mesylate (DFOM)

A chelating agent which reacts with ferric ion to form a

1:1 chelate known as ferrioxamine

Marketed as Desferal Injection (Ciba)

Produced by Streptomyces pilosus

Chronic iron toxicity

• causes

• hereditary hemochromatosis

• hemosiderosis

• symptoms

• cirrhosis: iron deposition in the liver

• diabetes: iron deposit in the pancreas (damage to

• 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

Copper (Cu)

• Deficiency

– decreased iron absorption

– neutropenia and leukopenia

• 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

• 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

• 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)

• 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

• Nausea and vomiting

• Changes in hair color

• Sources: blueberries, wheat bran, beet greens,

lettuce, legumes, fruit

• RDA: 2.5 – 5.0 mg

• 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

• 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)

• 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

enzymes:heme oxygenase and

• essentiality exists in some animals for

ionic cobalt (sheep and cattle)

• in rats administration of cobalt produces

• 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

• Widely found in commonly used foods

(cereals, vegetables

• Mo is part of flavoproteins, xanthine

oxidase, aldehyde oxidase

• 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