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 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

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

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– 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

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: 9%

• calcium lactate 13%

• calcium carbonate 40%

• dibasic calcium phosphate 30%

• calcium glucobionate 6%

• calcium chloride 27.2%

• calcium levulinate 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 non-heme

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

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

Fe++

Fe+++

APOFERRITIN

FERRITIN

mucosal cell (upper smallintestine)

gastric HCl, ascorbic acid

intestinalsecretion1-2 mg/day

Fe+++ - transferrin

plasma

apotransferin

Fe++ - hemoproteins(hemoglobin, myoglobin

Fe+++ - ferritin

Fe+++ - hemosiderinbone marrowmuscle

liver

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

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 20%

• Exsiccated ferrous sulfate

• ferrous gluconate 11.6%

• ferrous fumarate 33%

• ferrocholinate 12%

• polysaccharide-iron complex

• iron dextran (Imferon)

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)

(CH2)5H2N N

C(CH2)2

CN

(CH2)5N

O O

OH H C(CH2)2

CO

N

O

OH (CH2)5N

CCH3

O

OH

H

A chelating agent which reacts with ferric ion to form a1:1 chelate known as ferrioxamineMarketed 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

• sources• liver, shellfish, whole grains, cherries, legumes,

nuts

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 oxidation-reduction 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