Unit 9: Minerals

1. Unit 9: Minerals

2. Topics to cover • Definitions • Macrominerals vs microminerals • Macronutrients vs micronutrients • General absorption of minerals • Functions, deficiencies & homeostasis of minerals • Calcium • Iron • Zinc • Copper • Iodine • Selenium • Antioxidants • Why do mineral deficiencies occur? Strategies to alleviate worldwide deficiencies

3. Definitions Macrominerals vs microminerals Macronutrients vs micronutrients

4. Macro vs microminerals • Macrominerals: • Include calcium, phosphorus, magnesium, sodium, potassium and chloride • Macrominerals are required in amounts greater than 100 mg/day • Microminerals: • Include iron, zinc, copper, selenium, chromium, iodine, manganese, molybdenum, fluorine, nickel, silicon, vanadium, arsenic, boron, cobalt. • Required in small quantities • Microminerals are also known as ‘trace elements’

5. Macro vs micronutrients • Macronutrients include: • Protein • Lipids • Carbohydrates • Micronutrients include: • Minerals (macrominerals & microminerals) • Vitamins (fat and water soluble) • Units 7 & 8 cover vitamins • Unit 9 covers minerals

6. General absorption of minerals

7. Digestion/absorption • Unlike macronutrients (i.e. protein, fat, carbohydrates), micronutrients do not require enzymes for them to be absorbed. • Sometimes minerals are bound to proteins, and enzymatic digestion of the protein might help in the release of the mineral. • Sometimes minerals are found as salts.

8. pH affects absorption of some minerals • Some minerals (Ca, Fe, Zn, Cu) are present in foods as insoluble salts. • Minerals from foods are solubilized in the stomach thanks to the acidity (HCl). • When we take an antacid with our foods, we do not favor the solubility and absorption of minerals. Why? pH of stomach is increased. • This solubility does not last long, since the intestine is more alkaline (pH ~7). • In alkaline environments, minerals tend to precipitate and not be absorbed (instead are excreted). • Precipitation of minerals will not happen depending on the presence of certain food components that bind to the mineral, and enhance its absorption (‘enhancers’) • There are also mineral ‘inhibitors’.

9. Foods components affect the absorption of some minerals • Calcium absorption: • Enhanced by lactose (sugar in milk) • Inhibited by fiber and phytate • Enhanced by vitamin D • Inhibited by fat • Iron absorption: • Enhanced by vitamin C and meat • Inhibited by fiber, phytate, tannins (tea), oxalate (spinach) and certain proteins (soy protein, egg protein, casein) • Zinc absorption: • Inhibited by fiber, phytate and tannins (tea) and oxalate (spinach)

10. Oxalate (or oxalic acid) present in foods like chocolate and spinach binds to minerals and inhibits their absorption. • Likewise, phytate (or phytic acid) present in many plant crops, is a mineral inhibitor.

11. Just like certain nutrients affect mineral absorption, certain minerals and nutrients affect the action of common drugs.

12. Minerals might compete for absorption at the intestinal site • Magnesium vs calcium • Phosphorus vs calcium (a dietary intake of 1:1 is recommended) • Iron vs zinc

13. Functions, deficiencies & homeostasis of minerals

14. CALCIUM (Ca)

15. Calcium • Calcium participates in important functions: • nerve transmission • muscle contraction • synthesis of hormones and enzymes • mineralization of bones • clotting of blood • When we don’t have enough calcium in our blood, our bones are ‘stripped’ from their Ca. • 99% of our body Ca is in our bones. • This can lead to osteoporosis (insufficient bone mineralization).

16. Calcium homeostasis • Regulation of calcium involves 3 hormones: • parathyroid hormone (produced by parathyroid gland) • 1,25-(OH)2 vitamin D3 (synthesized in kidneys) • calcitonin (produced by thyroid gland) • Together, they play a major role in keeping plasma calcium levels at a constant level.

17. Calcium homeostasis by PTH • When plasma calcium falls below the normal standard (10 mg/100 mL), the parathyroid gland secretes PTH (parathyroid hormone). • PTH acts on the kidney: • It converts an inactive form of vitamin D into the active form 1,25-(OH)2 vitamin D3 (known as calcitriol) • It stimulates the kidney to conserve Ca (not eliminate it in urine) • PTH acts on the bone: • It stimulates the mobilization of Ca away from the bone

18. Calcium homeostasis by calcitriol • Calcitriol (1,25-(OH)2 vitamin D3) is the active form of vitamin D • Calcitriol acts on intestine: • It stimulates the absorption of Ca by the intestine • Calcitriol acts on bones: • It mobilizes calcium away from the bone • Estrogen enhances calcium absorption indirectly by enhancing 1,25-(OH)2 D3 production in the kidney. • This explain why long hormone replacement therapy (HRT) in menopausal women appears to be valuable in preventing bone fractures that stem from osteoporosis.

19. Increased bone resorption= increased Ca losses from bone.

20. Calcium homeostasis by calcitonin • When plasma calcium levels rise above normal, the thyroid gland secretes calcitonin (a hormone) • Calcitonin functions by depositing calcium on the bone. • In this way, calcium levels in the plasma go down. • Thus, calcitonin promotes the mineralization of bones.

21. IRON (Fe)

22. Iron • Iron deficiency is the micronutrient deficiency most prevalent in the world. • It is followed by vitamin A, iodine and zinc. • Iron is a part of heme present in: • hemoglobin (which transports oxygen in blood) • myoglobin (which stores oxygen in muscle) • cytochromes involved in the electron transport chain (unit 6) and in cytochrome P450 (involved in metabolism of drugs, pesticides, carcinogens, alcohol metabolism) • Iron is also forms part of many metalloenzymes involved in many reactions occurring in the body.

23. Iron deficiency • Deficiency of iron can lead to fatigue, anemia (where hemoglobin levels drop below 120 g/dL), poor school performance and poor immunity, brain function, premature birth, death. • Iron deficiency most evident: • pre-menopausal women (due to menstrual losses each month) • pregnant women (due to expanding blood volume) • infants and children (rapid growth rates, thus high Fe needs)

24. Ferritin • Storage form of Fe in body is called ferritin. • Infants are born with high ferritin levels, which are their sources of Fe for the 1st six months of life • After the 6th month, when storage of Fe goes down, pediatricians recommend feeding complementary foods enriched with Fe (purees, infant cereals, formulas) • Human milk (the gold standard for infant nutrition) not a great source of Fe (0.5 mg-0.3 mg/L), however it is more absorbable than cow milk. Human milk Fe is 50% absorbable vs cow milk Fe which is 10% absorbable.

25. To determine Fe status • To determine the Fe status of an individual, the following tests can be performed: • Serum ferritin (this is proportional to the storage levels in the body; low levels correspond to a low Fe status) • Problem with this test is that it is affected by infection, fever, liver disease. • Transferrin saturation (transferrin is the blood protein that binds and carries Fe to the tissues; low saturation levels mean low Fe status). • Transferrin receptors (transferrin-Fe bind to transferrin receptors in cells; high levels of transferrin receptors correspond to a low Fe status)

26. Toxicity • Toxicity could occur due to (a) oversupplementation, (b) repeated blood transfusions, or (c) a genetic disease that predisposes individual to absorb Fe (hemochromatosis) • Fe deficiency is as deleterious to human health as iron overload. • Why? Fe participates in the Fenton reaction, which results in the production of free radicals. • These free radicals damage cell membranes (phospholipids), proteins and DNA/RNA.

27. Fenton reaction Fe2+ + H2O2--->  Fe3+ + .OH + OH- Hydroxyl anion Ferric iron Ferrous iron Hydrogen peroxide (common byproduct of metabolism) Hydroxyl radical (damaging to cell membranes, proteins and DNA)

28. ZINC (Zn)

29. Zinc • Zinc plays key roles in growth and immunity. • Zn deficiency leads to: • growth failure • susceptibility to infections • complications during childbirth • may be a particular problem for those with HIV infection • Zn supplementation of at-risk populations leads to improved growth. • Zn supplementation reduces the mortality of diarrheal diseases and lowers the incidence of respiratory tract pneumonia, two of the most common causes of death in children in developing countries.

30. How to determine Zn status? • It is difficult to determine whether a person is zinc deficient. • Measuring Zn levels in blood is not reliable, since zinc changes with the time of the day. It has a circadian rhythm. Zn levels are also affected by illness and periods of rapid growth. • Others methods involve: • Measuring levels of alkaline phosphatase or alcohol dehydrogenase in blood which are enzymes that require zinc • Zinc concentrations in hair • It is difficult to diagnose Zn deficiency since symptoms are similar to those of Fe deficiency.

31. Metallothionein (MT) • Just like ferritin is the storage form of Fe, metallothionein is the storage form of Zn in body. • However, it is not specific to Zn since it can also store cadmium, copper, selenium, mercury • Metallothionein is rich in cysteine (amino acid). • It has been hypothesized that a MT disorder explains several symptoms of autism (the mercury poisoning hypothesis), but a study (2006) found that autistic children did not differ significantly from normal children in levels of MT.

32. COPPER (Cu)

33. Copper • This mineral participates in many reactions: • Collagen synthesis, melanin (skin pigmentation) synthesis, cytochromes in respiratory chain, neurotransmitter synthesis • Once absorbed, copper binds to ceruloplasmin in blood. It is a Cu storage in tissues. • Besides acting as a Cu carrier & storage, ceruloplasmin is involved in Fe absorption. • Thus, Cu deficiency can lead to Fe deficiency • Cu deficiency is rare

34. Wilson’s disease • Wilson's disease is a genetic disorder in which copper accumulates in tissues. In this disease the individual has psychiatric symptoms and liver disease. • It is treated with medication that reduces copper absorption or removes the excess copper from the body, but occasionally a liver transplant is required.

35. Menkes disease • Menkesdisease is a genetic disorder that affects copper levels in the body, leading to copper deficiency. • It is characterized by sparse and coarse hair, growth failure, and deterioration of the nervous system. • Also known as ‘kinky hair disease’. • Results in death before the age of 3 yrs.

36. IODINE (I)

37. Iodine • Iodine forms part of two hormones synthesized by the thyroid gland. • Tetraiodothyronine (T4) • Triiodothyronine (T3) • Iodine is first incorporated into the thyroid gland, and binds to tyrosine (amino acid) residues of the protein thyroglobulin. • Further reactions, results in T3 and T4. • About 90% of the hormone released by the thyroid gland is T4, while 10% is T3.

39. Functions of T3 and T4 • Involved in protein synthesis; bone growth, neuronal maturation; cell differentiation; regulation of protein, carbohydrate and fat metabolism; regulation of vitamin metabolism. • Increases electron transport chain activity • This causes increased body heat production • Increased oxygen consumption Thyroid gland http://www.endocrineweb.com/thyfunction.html

40. Regulation of T3 and T4 • The thyroid gland is stimulated by TSH (thyroid stimulating hormone) secreted by the pituitary gland. • When T4 in blood are low, pituitary gland secretes TSH, which enlarges the thyroid gland. • When T4 in blood are normal or high, TSH secretion is stopped. • The pituitary gland is in turn affected by the hypothalamus, which secretes TRH (thyrotropin-releasing hormone) which enhances the synthesis and release of TSH by the pituitary.

41. http://www.endocrineweb.com/thyfunction.html

42. Iodine deficiency disorder (IDD) • Iodine deficiency is the most important cause of brain damage and mental retardation. • IDD consists of a wide spectrum of disorders ranging from simple goiter, characterized by an enlargement of the thyroid gland, to cretinism, an irreversible form of mental retardation. • About 740 million people are affected by goiter, and over 2 billion people are estimated to be at risk of IDD, particularly those living in countries where the soil and water iodine content are low such as India, Nepal, and China.

43. Goiter, characterized by an enlarged thyroid gland. When thyroid hormones are low, the pituitary gland secretes TSH which has the effect of enlarging the thyroid (this is to increase the surface area to “trap” iodine). Particularly prevalent in India, Nepal and China.

44. SELENIUM (Se)

45. Selenium • Selenium is incorporated into proteins to make selenoproteins, which are important antioxidant enzymes. • The antioxidant properties of selenoproteins help prevent cellular damage from free radicals. • Selenium also participates in thyroid hormone metabolism.

46. Glutathione peroxidase • Selenium is an important cofactor for the enzyme glutathione peroxidase (a selenoprotein). • This means that without Se the enzyme cannot function. • Glutathione peroxidase uses glutathione (tripeptide made of glycine, cysteine & glutamic acid) and catalyzes the reduction of hydrogen peroxide into water.

47. Glutathione peroxidase Oxidized glutathione Glutathione peroxidase 2 GSH + H2O2 GSSG + H2O Hydrogen peroxide- Damaging to cell membranes & DNA Water Reduced glutathione

48. Selenium sources (dependent on soil content) • The content of selenium in food depends on the selenium content of the soil where plants are grown or animals are raised. • Soil in the high plains of northern Nebraska and the Dakotas have very high levels of selenium. • Soils in some parts of China and Russia have very low amounts of selenium. • Selenium also can be found in meats and seafood. Animals that eat grains or plants that were grown in selenium-rich soil have higher levels of selenium in their muscle. • Nuts are good sources. http://ods.od.nih.gov/factsheets/selenium.asp

49. Antioxidants

50. Free radicals • Free radicals are atoms or molecules with an imbalance of electrons. • Examples of free radicals are: superoxide radical (O2-), peroxyl radical (O22-), hydrogen peroxide (H2O2), OH. (hydroxy free radicals), HO2. (hydroperoxyl radicals) • They are damaging to our bodies since they can attack DNA, proteins and polyunsaturated fatty acids (in our cell membranes). • Some of these radicals result from normal cellular processes.