1. Microminerals/Trace Elements
Minerals that comprise < 0.01% of the body weight
Needed in concentrations of 1 PPM (part per million) or less; < 100 mg needed per day
RDAs have been established for 6 of these elements
Iron, zinc, copper, iodine, selenium, and molybdenum
Adequate intakes have been estimated for three
Manganese, fluoride, chromium
Many are involved as cofactors in enzymes

2. Iron
Ferric (3+) and ferrous (2+) forms the only oxidation states found in the body and in food.
Food forms are either heme or non-heme iron
Heme forms (derived from hemoglobin and myoglobin) are found mostly in animal products
Non-heme forms are principally found in plants and require more digestion prior to absorption; supplements are generally nonheme iron
Many foods are fortified with iorn including flour, corn meal, and rice.
It supports fundamental biological functions involved in the handling and transport of oxygen, nitrogen fixation, detoxification, photosynthesis, and synthesis of DNA (Crichton and Ward, 1992). Iron is potentially toxic to cells (Wrigglesworth and Baum, 1980). Its toxicity derives from the catalytic production of free radicals through the Fenton and Haber-Weiss reactions (Wardman and Candeais, 1996). The essential/toxic nature of iron has resulted, through evolution, in molecular mechanisms that secure cell and body iron homeostasis.
Animal fourms are meat fish and poultry.
Nonheme is in nuts fruits begies grains tofu, and dairy products (poor source).
Table 12-2, p. 419

3. Digestion and Absorption
“Good” chelators:
Acids (ascorbic, citric, tartaric); sugars; meat products; mucin
“Inhibitors”: polyphenols such as those found in coffee and tea; oxalic acid; phytates; EDTA; calcium, zinc, manganese, nickel
Figure 12.2 Overview of iron digestion, absorption, and transport.
Digestion and Absorption
Heme iron must be digested from the globin portion of hemoglobin
Absorbed as heme into the enterocyte. Occurs throughout the intestine, but majority in the duodenum
In the enterocyte the prophryin ring is hydrolyzed by heme oxygenase into inorganic ferrous iron and protoporphyrin
The released iron my associate with proteins that make up the paraferritin complex and can be used by the intestinal mucosal cells
Nonheme iorn must be released by pepsin and proteases. O
Once released nonheme iron is present as ferric iron in the stomach. Some may be reduced to the ferrous state, and most ends up aas ferric hydroxide (fe(OH)3 in the alkaline environment of the intestine.
Ferric hydroxide is relatively insoluble that aggregates and precipitates, making iron less avaiable for absorption.
Frerrireductases found in the brush border (Dcytb - duodenal cytochrome b) function to reduce ferric iron to the ferrous state.
Absorption is best from an acidic environment and is facilitated by chelation of the iron with ligands that help solubilize the ferric iron. Some chelators help absorption, some inhibit it. Depends on solubility and tightness of iron binding to the chelator.
Several aa are thought to transport iron across the mucosal cell, including cytteine and histidine. It can also be bound to a protein called mobilferrin and shuttled across the intestinal enterocytes. Generally either reductases or other flavins or Vit C will reduce it to Fe2+. It is then bound to a transport protein in the basolateral membrane, called ferroportin. During this movement, it is ocidized to Fe3+ by a copper containing protein called hephaestin. In other body tissues, the protein is ceruloplasmin. Thus copper is required for iron absorption. Cu deficiency results in iron accumulation in the intestine and liver and a reduction of iron transport to tissues.
It is transported in the blood as a part of the protein transferrin. Made in liver, two binding sites for minerals. NH2 site will also bind chromium copper manganese, cadmium zinc nickel.
Ion must be bound to proteins as a protective mechanism. Unbound it can generates free hydroxyl radicals. Free iron can also be used by bacteria to promote growth, so binding prevents the spread of bacteria (infections)
Fig. 12-2, p. 421

4. Storage = liver, bone marrow, spleen
Ferritin is the storage form of iron. Up to 45oo iron atoms can be stored in one ferritin molecule. Ferritin is constantly being degraded and restored and provides a pool of available iron.
Storage = liver, bone marrow, spleen
p. 422

5. Cellular iron influences the synthesis of apoferritin at the translation level.
Release of iron from stores requires mobilization of Fe3+ and the use of reducing substances such as riboflavin, niacin, and/or vitamin C .
Uptake by tissues depends on the transferrin saturation level and the presence of a tranferrin receptor (TfR2) on the cell
Figure 12.4 The influence of intracellular iron on the translation of ferritin mRNA and transferrin receptor mRNA.
An iron regulatory/response element binding protein (IRE-BP) responds to the cell’s iron status. This IREBP’s ability to respond depends on the cell’s iron status. With lots of iron it exists as a 4FE-4S cluster and exhibits aconitase activity. With less iron, the protein exists as a 3FE-4S cluster and functions as a binding protein. As a binding protein, it binds to iron response elements located on the 5’ UTR of ferritin mRNA. IREs are stem loop structures of about 30 nucleotides found in the mRNA. In low iron situations, the IIRE-P acts as a binding protein and binds to the IRE in ferritin mRNA, and this binding acts as a repressor to inhibit the translation of ferritin protein. In the opposite situation, the IRE_BP exhibits aconitase activity. Without IRE_BP binding the ferritin mRNA undergoes translation. Thus, more ferritin protein is made.
Fig. 12-4, p. 426

6. Functions: Other Enzymes Energy Production
In heme proteins - hemoglobin, myoglobin, cytochromes, In iron-sulfur proteins - several in electron transport chain, aconitase and ferrochelatase
Other Enzymes
monooxygenases, dioxygenases, and oxidases,
aconitase (krebs cycle)
Peroxidases
oxidoreductases
Ribonucleotide reductase
Glycerolphosphate dehydrogenase
Figure 12.5 Heme biosynthesis. Vinyl group: CH=CH2 ; propionic acid group: (CH2)2COO-; acetate group: CH2COO-.
Monooxygenases indluce those from the synthesis of phenylalanine, tyrosine and tryptophan
Dioxygenases are used in amino acid metabolism, synthesis of carnitine, procollagen, and vitamin A. Also in the function of nitric oxide synthase
Peroxidases such as catalase converte hydrogen peroxide to water and molecular oxygen
Oxidoreductases work in the coversion of aldehyds to alcohols, sulfite to sulfate
Fig. 12-5, p. 428

7. Losses are from GI tract, skin, kidney
Figure 12.6 Internal iron exchange.
Daily needs cannot be met by absorbed iron. Therefore, it is highly conserved and recycled.
Losses are from GI tract, skin, kidney
Fig. 12-6, p. 432

8. Deficiency: Iron Deficiency and Iron Deficiency Anemia
Figure 12.7 Sequential changes in iron status associated with iron depletion. Source: Adapted from Victor Herbert, Recommended dietary intakes (RDI) of iron in humans, Am J Clin Nutr 1987;45:679–86 (© Am J Clin Nutr, American Society for Clinical Nutrition), and Victor Herbert, J Nut 1996;126: 1213S–20S. Used with permission.
Iron deficiency anemia is most often found in four populations: infants and young children, adolescents in their early growth spurt, females during childbearing years, pregnant women
Figure shows the gradual depletion ofiron content and demonstrates that anemia does not occur until iron depletion is severe. Iron deficiency without anemia can occur. Symptoms of iron deficiency include pallor, listlessness, behavioral disturbances, impaired performance in some cognitive tasks, some irreversible impairment in learning abiltiy, and short attention span.
Fig. 12-7, p. 433

9. Toxicity: Hemochromatosis or iron overload
Hereditary hemochromatosis (HHC) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and deposition in the liver, pancreas, heart, joints, and pituitary gland. Without treatment, death may occur from cirrhosis, primary liver cancer, diabetes, or cardiomyopathy. In 1996, HFE, the gene for HHC, was mapped on the short arm of chromosome 6 (6p21.3). Two of the 37 allelic variants of the HFE gene described to date (C282Y and H63D) are significantly correlated with HHC.
The HFE protein is a 343 residue type I transmembrane protein that associates with class I light chain beta2-microglobulin (4) . The HFE protein product binds to the transferrin receptor and reduces its affinity for iron-loaded transferrin by 5- to 10-fold (7) . The C282Y mutation alters the HFE protein structure and beta2-microglobulin association, disrupting its transport to and presentation on the cell surface (8)
Hereditary hemochromatosis is one of the most common genetic disorders in the United States. It most often affects Caucasians of Northern European descent, although other ethnic groups are also affected. About 5 people in 1,000 (0.5 percent) of the U.S. Caucasian population carry two copies of the hemochromatosis gene and are susceptible to developing the disease. One person in 8 to 12 is a carrier of the abnormal gene. Hemochromatosis is less common in African Americans, Asian Americans, Hispanic Americans, and American Indians.
Although both men and women can inherit the gene defect, men are about five times more likely to be diagnosed with the effects of hereditary hemochromatosis than women. Men also tend to develop problems from the excess iron at a younger age.
Joint pain is the most common complaint of people with hemochromatosis. Other common symptoms include fatigue, lack of energy, abdominal pain, loss of sex drive, and heart problems. Symptoms tend to occur in men between the ages of 30 and 50 and in women over age 50. However, many people have no symptoms when they are diagnosed.
If the disease is not detected early and treated, iron may accumulate in body tissues and may eventually lead to serious problems such as
* arthritis
* liver disease, including an enlarged liver, cirrhosis, cancer, and liver failure
* damage to the pancreas, possibly causing diabetes
* heart abnormalities, such as irregular heart rhythms or congestive heart failure
* impotence
* early menopause
* abnormal pigmentation of the skin, making it look gray or bronze
* thyroid deficiency
* damage to the adrenal gland

10. Zinc
Found in all organs and tissues; highest in bone, liver, kidney, muscle and skin
Can exist in different valence states but in the body is always found in its divalent form (Zn2+)
Found in many sources, but zinc from plant sources is lower in content and not as easily absorbed as Zn associated with meat.
Table 12-3, p. 436

11. Figure 12.8 Digestion, absorption, enterocyte use, and transport of zinc. Abbreviation: CRIP, cysteine-rich intestinal proteins.
Enhancers of absorption: citric acid, picolinic acid, histidine, cysteine, glutathione, low zinc status
Inhibitors: phytate, oxalate, polyphenols, fibers, folic acid, divalent cations
Fig. 12-8, p. 438

12. Figure 12. 10 Uptake, storage and use of zinc in cells
Figure Uptake, storage and use of zinc in cells. Abbreviations: MRE, metal regulatory elements; MTF, metal transcription factor.
Zince is carried in the blood on a number of carrier proteins. Albumin is thought to carry about 60%. Zinc transporters help enter the cell, some are generalized, some tissue specific. Zinc is thought to be stored in most tissues as part of the protein thionein, which when mineral bound is known as metallothionein. Metallothionein is found in most tissues of the body, including the liver. Zinc and possibly other minerals may affect the gene expression of thionein. Metal regulatory elements (MREs) are found in the promoter region of the thionein gene. Zinc may interact with the MREs alone or through a transcription factor (metal transcription factor) to induce thionein synthesis. Thionein gene expressionis also influences by glucagon and interleukin 1 (thought to induce during infection). During infection plasma zinc concentrations typically decrease and liver stores increase. Zinc thus cannot be used for bacterial replication.
Release of zinc from metallothionein involves lysosomal proteases. At an acid pH, these proteases degade metallothionein to release the apoprotein thionein and zinc, whichis then available for use by cells of other tissues.
Fig , p. 440

13. Alcohol dehydrogenase Superoxide dismutase
Carbonic anhydrase
Alkaline phosphatase
Alcohol dehydrogenase
Superoxide dismutase
Carbonic anhydrase, reaction allows rapid disposal of CO2. Makes buffering agents for the blood.
Alkaline phosphatase
Involved in at least 70 and probably as many as 200 different reactions. Is a part of more enzyme systems than all the other trace elements combined.
Table 12-4, p. 441

14. Table 12-5, p. 446

15. Figure 12.12 Overview of copper digestion, absorption, enterocyte metabolism, and transport.
Fig , p. 447

16. Figure 12.13 Transport, uptake, and metabolism of copper in hepatocytes and extrahepatic cells.
Fig , p. 450

17. p. 451a

18. p. 451b

19. p. 452a

20. p. 452b

21. p. 452c

22. Figure 12.14 Selenomethionine and selenocysteine.
Fig , p. 456

23. Figure Overview of selenium digestion, absorption, and transport. Abbreviations: VLDL, very low density lipoprotein; LDL, low-density lipoprotein.
Fig , p. 457

24. Figure 12.16 Selenium metabolism.
Fig , p. 458

25. p. 459a

26. p. 459b

27. p. 459c

28. p. 460a

29. p. 460b

30. Figure 12. 17 Tetra-aquo dinicotinato chromium complex
Figure Tetra-aquo dinicotinato chromium complex. Water molecules are believed to be replaced by amino acids (glutamic acid, cysteine, and glycine) to stabilize the complex. Source: From Nutrition Reviews 33(1975):129–35. © International Life Sciences Institute—Nutrition Foundation. Used with permission.
Fig , p. 464

31. Figure Proposed interaction of Cr as part of GTF and insulin and cell’s insulin receptor. Source: Modified from Mertz W, Toepfer EW, Roginski EE, Polansky MM. Present knowledge of the role of chromium. Fed Proc 1974;33:2276.
Fig , p. 464

32. Figure Proposed role of chromium (Cr3+) as part of chromodulin in potentiating insulin’s actions.
Fig , p. 465

33. Figure 12.20 Digestion and absorption of iodine.
Fig , p. 468

34. Figure Overview of iodine intrathyroidal metabolism and hormonogenesis, and thyroid transport and cellular uptake. Abbreviations: T4, 3,5,3’,5’-tetraiodothyronine; T3, 3,5,3‘-triiodothyronine; rT3, reverse T3; Thg, thyroglobulin; MIT, 3-monoiodotyrosine; DIT, 3,5-diiodotyrosine.
Fig , p. 469

35. p. 470

36. Figure 12.22 The structures of MIT, DIT, T3, and T4.
Fig , p. 470

37. Figure Goitrin.
Fig , p. 471

38. p. 472

39. Table 12-6, p. 473

40. p. 474

41. Figure 12.24 Molybdopterin structures.
Fig , p. 478

42. p. 478

43. Figure The actions of xanthine dehydrogenase and xanthine oxidase on the substrate hypoxanthine.
Fig , p. 479

44. Figure The actions of xanthine dehydrogenase and xanthine oxidase on the substrate hypoxanthine.
Fig a, p. 479

45. Figure The actions of xanthine dehydrogenase and xanthine oxidase on the substrate hypoxanthine.
Fig b, p. 479

46. Table 12-7, p. 481

47. Table 12-1a, p. 418

48. Table 12-1, p. 418

49. Table 12-1b, p. 418