Minerals

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)

Minerals
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

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

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

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

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

Functions of minerals
provide a suitable medium for cellular activity 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
permeability of membranes irritability of muscles and nerve cells

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

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)

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)

The electrolytes
There are 3 major electrolytes:
sodium potassium chloride

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

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)
RDA for adults: 1.1 to 3.3 gm/day sodium deficiency:
dehydration acidosis tissue atrophy

sodium excess:
edema (hypertonic expansion ) hypertension

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

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

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

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

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)

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)

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)

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

Chloride (Cl)
Deficiency of chloride:
hypochloremic alkalosis hypovolemia pernicious vomiting psychomotor disturbances

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

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)

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

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

Calcium supplements
calcium gluconate: calcium lactate calcium carbonate dibasic calcium phosphate calcium glucobionate calcium chloride calcium levulinate 9% 13% 40% 30% 6% 27.2% 13%

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)

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)

Phosphorus
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 (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)

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

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

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

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

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 nonheme

Food iron
heme iron
meats poultry fish

non-heme iron
vegetables fruits legumes nuts breads and cereals

20-23% of heme-iron is absorbable

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

FOOD IRON gastric HCl, ascorbic acid Fe ++ unabsorbed Fe (fecal excretion) mucosal cell (upper small intestine)

Fe+++ APOFERRITIN

FERRITIN intestinal secretion 1-2 mg/day Fe +++ - transferrin

apotransferin plasma

Fe++ - hemoproteins (hemoglobin, myoglobin bone marrow muscle

Fe +++ - ferritin Fe +++ - hemosiderin liver

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

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)

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

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

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 minimizes tatoo

oral iron causes black stools, constipation, cramping do not administer with antacids or metal chelators (tetracyclines)

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)

O H2N (CH 2)5 C N OH O C (CH 2)2 N H O H (CH 2)5 OH N N C O (CH 2)5 C N OH CH3

C O (CH 2)2

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 beta cells) skin pigmentation cardiac failure

treatment: phlebotomy ( 1 unit of blood removes

about 250 mg of iron

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

Copper (Cu)
Deficiency
decreased iron absorption neutropenia and leukopenia bone demineralization failure of erythropoiesis
liver, shellfish, whole grains, cherries, legumes, nuts

sources

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

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

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)

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

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

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

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

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)

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 enzymes:heme oxygenase and cytochrome P-450 largest quantities are found in kidneys and skin human intake: ~ 1.5 - 3.5mg/day

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

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 oxidationreduction catalyst

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

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