MINERALS

1. M.Prasad Naidu MSc Medical Biochemistry, Ph.D,. MINERALS

2. 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)

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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)

11. 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

12. 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)

13. The electrolytes • There are 3 major electrolytes: • sodium • potassium • chloride

14. 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

15. 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

16. Sodium (Na) • RDA for adults: 1.1 to 3.3 gm/day • sodium deficiency: • dehydration • acidosis • tissue atrophy • sodium excess: • edema (hypertonic expansion ) • hypertension

17. 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

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

19. 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

20. 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

21. 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)

22. 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)

23. 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)

24. 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

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

26. 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

27. 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)

28. 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)

29. 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

30. 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

31. 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%

32. 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)

33. 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)

34. 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

35. 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

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

37. 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)

38. 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

39. 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

40. 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

41. 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

42. Zinc supplements

43. 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

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

45. 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

46. 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

47. 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)

48. 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

49. 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

50. 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