Chapter 13: Essential Trace & Ultratrace Minerals

Mineral Functions: Match each mineral with a representative enzyme and the functional system for which that mineral is important. 1. iron 2. zinc 3. copper 4. selenium 5. manganese a. superoxide dismutase and protection of mitochondrial integrity b. myeloperoxidase and immune function c. carbonic anhydrase and respiration d. dopamine monooxygenase and nerve function e. glutathione peroxidase and protection from oxidant damage

1. B Myeloperoxidase (also called chloroperoxidase), another heme-containing enzyme, is found in the plasma as well as in neutrophils (white blood cells). During phagocytosis, myeloperoxidase is released into the phagocytic vesicle within the neutrophil. 2. C Carbonicanhydrase has a very high affinity for zinc, which plays a catalytic role. The enzyme, found primarily in erythrocytes and in renal tubule cells, is essential for acid-base balance/buffering and respiration. 3. D To synthesize norepinephrine from dopamine, the enzyme dopamine monooxygenase/hydroxylase, which contains up to eight copper atoms per molecule, is required for the hydroxylation reaction. 4. E One of the most clearly established functions of selenium is as an integral part of the enzyme glutathione peroxidase. 5. A Superoxide dismutase, a manganese-dependent (Mn3+-SOD) oxido-reductase metalloenzyme (not manganese activated), functions in a manner similar to copper- and zinc-dependent superoxide dismutase to prevent lipid peroxidation by superoxide radicals.

True or False: Zinc fingers are involved in gene expression by playing a structural role in nuclear binding proteins such as RAR; thus, RAR is a metalloenzyme.

False Explanation: A metalloprotein, not metalloenzyme.

True or False: Regulation of translation is not a mechanism for nutrients to induce protein synthesis.

False Explanation: Iron does.

True or False: Iron regulatory protein (IRE-BP) is activated (i.e., to bind IREs) by iron.

False Explanation: Iron inactivates IRE-BP.

True or False: As cofactors for proteins, minerals only serve a catalytic role.

False Explanation: Minerals can be involved in structure, transport, etc.

True or False: Metallothionein is a storage protein for excess zinc, copper, and iron.

False Explanation: Zn and Cu, not Fe.

True or False: Albumin carries zinc and copper in the portal circulation to all tissues in the body.

True

True or False: Copper deficiency can result in iron deficiency due to an inability to oxidize iron (i.e., Fe+++), required for transport by transferrin.

True

True or False: Endocytosis is the mechanism for a transferrin receptor transporting iron into a cell.

True

True or False: Hemochromatosis is a genetic disorder that ultimately results in the excessive accumulation of iron in certain tissues.

True

True or False: Overall, assessing the status of a given mineral is difficult and requires multiple measures.

True

True or False: Zinc deficiency could result in a secondary deficiency of folate, because polyglutamate hydrolase is a zinc-containing enzyme.

True

Which statement about selenium metabolism is true? a. Free selenide can be converted into selenophosphate. b. Selenocysteine is degraded to yield selenomethionine. c. Dietary selenocysteine can be utilized directly to produce selenium-dependent enzymes. d. Significant cellular damage occurs only with complete cessation of selenoprotein synthesis.

a. Free selenide can be converted into selenophosphate. Selenide may be methylated for excretion or may be utilized to form selenophosphate Selenomethionine, which is derived from the diet, maybe either stored as selenomethionine in an amino acid pool, used for protein synthesis just as the amino acid methionine is used, catabolized in multiple reactions (referred to as transselenation) to yield selenocysteine, or directly lysed at the γ-position to generate selenide. Selenocysteine, which is derived either from selenomethionine metabolism or from the diet, is degraded primarily by selenocysteine β-lyase to yield free selenide.

Nutrient-drug interactions caused by antacids used to treat GERD are most likely to result in: a. poor absorption of nutrients such as iron. b. poor absorption of the drug when taken with grapefruit. c. enhanced metabolism of the drug rendering it less effective when taken on an empty stomach. d. enhanced excretion of potassium and other electrolytes.

a. poor absorption of nutrients such as iron.

In the presence of low intracellular iron, the binding of iron regulatory protein (IRE-BP) to iron response elements (IRE) present on the ferritin mRNA: a. results in a decrease in ferritin abundance. b. results in an increase in ferritin abundance. c. occurs only when intracellular iron concentrations are high. d. doesn't occur.

a. results in a decrease in ferritin abundance. In the case of ferritin in low-iron situations, the IRE-BP binds to an IRE in the 5' untranslated region of ferritin mRNA and acts as a repressor to inhibit the translation of the ferritin protein. Thus, less ferritin is made in cells when the cellular iron content is low. From a physiological standpoint, this inhibition makes sense because ferritin stores iron, and not much ferritin would be needed if the cell's iron content were low.

Which statement is false? a. Hemosiderin is the primary storage form of iron in cells. b. Iron is stored mainly in the liver, bone marrow, and spleen. c. Iron is released more slowly from hemosiderin than from ferritin. d. Ferritin is an unstable compound that is constantly being degraded and resynthesized.

a. Hemosiderin is the primary storage form of iron in cells. (Ferritin is the primary storage form of iron in cells) Iron not needed in a functional capacity is stored in three main sites: the liver, bone marrow, and spleen. Transferrin delivers iron to these sites, especially the liver, which is thought to store about 60% of the body's iron in both reticuloendothelial (RE) cells and hepatocytes. The remaining 40% is found in reticuloendothelial cells within the spleen and bone marrow (and possibly between muscle fibers). Ferritin is not a stable compound but rather is constantly being degraded and resynthesized, providing an available intracellular iron pool. Hemosiderin is another iron storage protein. Hemosiderin is thought to be a degradation product of ferritin, representing, for example, aggregated ferritin or a deposit of degraded apoferritin and coalesced iron at- oms. The content of iron in hemosiderin may be as high as 50%. The ratio of ferritin to hemosiderin in the liver varies according to the level of iron stored in the organ, with ferritin predominating at lower iron concentrations, and hemosiderin predominating at higher concentrations (iron overload). Although iron in hemosiderin can be labilized to supply free iron, iron is released at a slower rate from hemosiderin than from ferritin.

Chromium absorption is inhibited by _____ and enhanced by _____. a. antacids, picolinate b. methionine, phytic acid c. picolinic acid, vitamin C d. phenylalanine, histidine

a. antacids, picolinate Within the stomach, amino acids or other ligands may chelate chromium. Amino acids such as phenylalanine, methionine, and histidine as well as picolinic acid (picolinate) act as ligands to improve chromium absorption. This reaction, which occurs more readily with antacid use (e.g., to relieve heartburn), results in chromium precipitation and thus reduced absorption. Phytic acid, found mostly in grains and legumes, also diminishes chromium absorption; however, the quantity of phytic acid provided in most U.S. diets is not thought to substantially inhibit the absorption of dietary chromium.

Which mineral is thought to potentiate the action of insulin? a. chromium b. manganese c. copper d. cobalt

a. chromium While it is still thought to potentiate the action of in- sulin, more recent studies have suggested that the biologically active form of chromium is a low-molecular-weight chromium-binding substance called chromodulin. Chromodulin is thought to be produced in response to insulin secretion, which stimulates chromium uptake by cells.

Iodine deficiency associated with growth problems results in _____. a. cretinism b. Keshan disease c. goitrin d. goiter

a. cretinism Iodine deficiency in a fetus results from iodide deficiency of the mother; two types of cretinism can result. Neurological cretinism in the infant is characterized by mental deficiency, hearing loss or deaf mutism, and motor disorders such as spasticity and muscular rigidity. Hypothyroid cretinism results in thyroid failure. Early treatment of cretinism with iodine can often correct the condition.

Where would you find iron regulatory element binding protein (IRE-BP)? a. cytosol b. nucleus c. mitochondria d. none of the above

a. cytosol In cells, iron is incorporated into binding proteins (called iron regulatory/response element binding proteins [IRE-BP] or iron response proteins [IRP]), which affect the translation of mRNA for proteins involved in intestinal iron absorption, cellular iron uptake, and storage (Figure 13.4). With little avail- able cellular iron, the IRE-BP exists as a 3Fe-4S cluster and functions as a binding protein. As a binding protein, the IRE-BP binds to iron response elements (IREs), which are stem loop structures of about 30 nucleotides located in specific 3' and 5' untranslated regions of mRNA. IREs are present in the mRNA for several proteins involved in iron utilization, such as transferrin receptors, ferritin, cytochrome b reductase, and DMT1.

People living in regions that contain high soil molybdenum levels may develop _____. a. gout b. heart disease c. reduced urea production d. cretinism

a. gout However, symptoms such as gout (inflammation of the joints caused by the accumulation of uric acid) have appeared in some people living in regions that contain high soil molybdenum levels and in those with occupational exposure to molybdenum. Gout results from high amounts of uric acid (which likely arise from increased xanthine dehydrogenase activity) that have accumulated in and around joints.

Absorption of dietary iron is regulated by _____, produced by the liver when iron stores are high and released to the blood to act at the surface of enterocytes and macrophages. a. hepcidin b. hepaestin c. ferroportin d. hemoglobin

a. hepcidin The main regulator of iron absorption is the protein hepcidin, which is released from the liver when body iron stores are adequate or high. The liver is thought to recognize the body's iron status, at least in part, by the binding of diferric transferrin to transferrin receptors 1 (TfR1) found on liver cells. This binding in turn releases a high- iron (HFe) protein from TfR1; this released HFe protein then binds to hepatic TfR2, another type of transferrin receptor. The HFe-TfR2 complex is thought to serve as a "sensor" of the body's iron status and in turn stimulates hepcidin synthesis through an intracellular signaling pathway.

Nutrient-drug interactions caused by consuming amines in foods such as aged cheeses with monoamine oxidase inhibitors used to treat depression are most likely to result in: a. high blood pressure and cardiac dysrhythmia. b. poor absorption of the drug when taken with grapefruit. c. enhanced metabolism of the drug rendering it less effective when taken on an empty stomach. d. enhanced excretion of potassium and other electrolytes.

a. high blood pressure and cardiac dysrhythmia.

What two minerals can cause damage to cells when in their free ion forms? a. iron and copper b. zinc and molybdenum c. iodine and manganese d. zinc and copper

a. iron and copper When iron is left unbound, its redox activity can lead to the generation of harmful free radicals. As a pro-oxidant, copper (if free) behaves similarly to iron. Copper reacts with superoxide radicals and catalyzes the formation of hydroxyl radicals through the Fenton reaction: Cu1+ + H2O2 Cu2+ + OH- + •OH. Associated with the generation of reactive oxygen species is increased oxidative damage to DNA (base oxidation and strand breaks), proteins, and lipids (peroxidation), especially membrane lipids.

Glutathione loses two electrons when it acts as an antioxidant. Glutathione is _____. a. oxidized b. reduced

a. oxidized

Which trace mineral participates in the greatest number of enzyme systems? a. zinc b. iron c. selenium d. copper

a. zinc

Iron content of the average Western diet is estimated to be about a. 1 to 4 mg iron per 1,000 kcal. b. 5 to 7 mg iron per 1,000 kcal. c. 8 to 15 mg/day. d. 18 g /day.

b. 5 to 7 mg iron per 1,000 kcal. Although iron is widely distributed in food, its content in an average American diet is estimated at 5 to 7 mg iron per 1,000 kcal.

The primary physiological role of which mineral is as a constituent in the thyroid hormones? a. fluorine b. iodine c. selenium d. chromium

b. iodine The main function of iodide is in the synthesis of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). As long as the daily iodide intake is above about 50 μg, uptake of iodide by the thyroid gland is usually sufficient for hormone production

ZIP4 a. mutations result in zinc toxicity due to acrodermatitis enteropathica. b. is the primary transporter of zinc into enterocytes. c. is expressed only in the liver. d. degrades more rapidly when zinc intakes are low.

b. is the primary transporter of zinc into enterocytes. The protein carrier Zrt- and Irt-like protein (ZIP) 4 is the major transporter of zinc across the brush border membrane and into the cytosol of the enterocyte; this transporter is expressed throughout the gastrointestinal tract. Zinc intake influences ZIP4. With high zinc intakes, ZIP4 is degraded more rapidly to down-regulate absorption, whereas zinc restriction enhances ZIP4 mRNA stability, rapidly induces ZIP4 synthesis, and shifts ZIP4 proteins to the brush border membrane.

Which mineral serves as a cofactor in xanthine oxidase in the metabolism of purines, pyrimidines, and pteridines? a. manganese b. molybdenum c. copper d. chromium

b. molybdenum Xanthine dehydrogenase and xanthine oxidase (also called oxidoreductases) are interconvertible, iron-dependent (containing 2 iron-2 sulfur centers) enzymes that exist as a homodimer of two identical subunits and that also require FAD and molybdopterin in the oxosulfido cofac- tor form. The molybdenum is necessary for the oxidative capacity of the enzyme; inactivation of the enzyme results if the mineral is not present. Xanthine dehydrogenase is found in a variety of tissues, including the liver, lungs, kidneys, and intestine. Xanthine oxidase is found in the intestine, thyroid cells, and possibly other tissues.

The binding of iron by proteins defends the cells against a. iron deposition in kidneys and other organs. b. oxidative damage from free radicals. c. tissue hypoxia. d. stellate cells.

b. oxidative damage from free radicals. The role of proteins in the transport as well as stor- age of iron is important because of iron's redox activity. The binding of iron by proteins serves as a protective mechanism. When iron is left unbound, its redox activity can lead to the generation of harmful free radicals. Free ferrous iron (Fe2+), for example, readily reacts with hydrogen peroxide (H2O2) in what is known as the Fen- ton reaction: Fe2+ + H2O2 Fe3+ + OH− + •OH. This reaction generates a hydroxyl anion and a free hydroxyl radical (•OH), which is extremely reactive and damaging to cells.

Nutrient-drug interactions caused by drugs such as statins used to treat cardiovascular disease are most likely to result in: a. poor absorption of vitamins. b. poor metabolism of the drug when taken with grapefruit. c. enhanced metabolism of the drug rendering it less effective when taken on an empty stomach. d. enhanced excretion of potassium and other electrolytes.

b. poor metabolism of the drug when taken with grapefruit.

Which mineral is an essential factor in the action of glutathione peroxidase (GPX) in the reduction of organic peroxides and hydrogen peroxide? a. molybdenum b. selenium c. silicon d. vanadium

b. selenium One of the most clearly established functions of selenium is as an integral part of the enzyme glutathione peroxidase. Several glutathione peroxidase enzymes (designated GPX followed by a number) have been characterized, and each catalyzes the same basic reaction but in different tissues. Most GPXs (of which seven have been identified) are selenium dependent, containing selenium as selenocysteine.

At the cellular level, which mineral interacts with vitamin A by promoting growth and helping to synthesize retinol-binding protein? a. cobalt b. zinc c. silicon d. chromium

b. zinc

Excessive intake of non-heme iron interferes with absorption of which mineral by an unknown mechanism? a. manganese b. zinc c. chromium d. selenium

b. zinc Another interaction involves iron and zinc. Just as zinc inhibits iron absorption, iron inhibits zinc absorption. The inhibition occurs primarily if the two minerals are ingested together in the absence of food and if iron is present as nonheme iron in a ratio with zinc of 2 (or higher):1.

The following vitamins/ minerals are required for heme synthesis: a. vitamin E, vitamin C, and iron. b. folate, B12, and iron. c. B6, zinc, and iron. d. copper, zinc, and folate.

c. B6, zinc, and iron. To synthesize heme for hemoglobin, iron is needed in the erythropoietic cells in the bone marrow. Glycine and succinyl-CoA combine to form ∆-amino- levulinic acid (ALA) in the cell's mitochondria. The reaction is catalyzed by ∆-aminolevulinic acid synthase, a vitamin B6-dependent enzyme that is inhibited by the final end product (heme) and whose synthesis is also thought to be regulated by iron. Next, ALA enters the cytosol, where a zinc-dependent dehydratase catalyzes the condensation of two ALA molecules to form porphobilinogen. This enzyme is sensitive to lead, which binds to its sulfhydryl groups to inactivate the enzyme.

When superoxide radicals accumulate, superoxide dismutase catalyzes the formation of hydrogen peroxide. What happens to the hydrogen peroxide? a. It freely dissociates to water. b. It is excreted in the urine and through the lungs. c. It is converted to water and oxygen via catalase or glutathione peroxidase. d. It is used in the synthesis of DNA and RNA.

c. It is converted to water and oxygen via catalase or glutathione peroxidase. Hydrogen peroxides are generated in many cells throughout the body as part of normal metabolism and may be generated in large amounts by activated white blood cells as they phagocytize foreign substances. The reaction catalyzed by glutathione peroxidase neutralizes or eliminates hydrogen peroxide and organic (including lipid) peroxides. In fact, glutathione peroxidase is more active than catalase in reducing organic peroxides and hydrogen peroxides. If not removed, these peroxides typically damage cellular membranes and other cell components including proteins and DNA.

Which vitamin may enhance copper reduction? a. niacin b. biotin c. ascorbic acid d. β-carotene

c. ascorbic acid

What glycoprotein serves as a transporter of copper, an antioxidant, and an oxidative enzyme? a. albumin b. globulin c. ceruploplasmin d. free amino acid

c. ceruploplasmin Ceruloplasmin is released into the blood from the liver and constitutes about 60% to 70% of circulating copper in the blood. Ceruloplasmin, a glycoprotein, is not simply a trans- porter of copper in the blood. It is also a multifaceted oxidative enzyme (oxidase) that is found in the blood and bound to cell surface receptors on the plasma membranes of cells. Another proposed function of ceruloplasmin is as an antioxidant or modulator of the inflammatory process. As modulators of the inflammatory process, acute-phase (also called reactant) proteins like ceruloplasmin increase in the blood in response to severe infections and other inflammatory events (such as injury).

Which mineral is critical for oxidizing iron to be bound by transferrin for delivery to the tissues from the gut and liver? a. zinc b. manganese c. copper d. chromium

c. copper Iron transport across the enterocyte's basolateral membrane for entrance into the blood requires the iron to bind to the membrane transport protein ferroportin (fp or fpn). This transport of iron is also coupled with iron's oxidation to Fe3+ by a copper-containing protein called hephaestin (or, in the absence of hephaestin, by the copper-containing protein ceruloplasmin). Hepha- estin is found on the enterocyte's basolateral membrane near ferroportin. This role of copper as part of hephaestin and ceruloplasmin in the oxidation of iron is crucial to iron metabolism. In fact, copper deficiency results in decreased ceruloplasmin and hephaestin, iron accumulation in the intestine and liver, and reduced iron transport to tissues. The copper-dependent oxidation of iron to the ferric state allows the transport of iron in the blood as part of the protein transferrin.

Zinc is important for taste perception as a component of _____. a. carbonic anhydrase b. alcohol dehydrogenase c. gustin d. thionein

c. gustin Zinc is also important for taste; it is a component of gustin, a protein involved in taste acuity.

Nutrient-drug interactions caused by anticonvulsants such as phenobarbital used to treat seizures are most likely to result in: a. poor absorption of nutrients such as iron. b. poor absorption of the drug when taken with grapefruit. c. reduced metabolism of vitamins. d. enhanced excretion of potassium and other electrolytes.

c. reduced metabolism of vitamins.

Which non-metal nutrient deficiency is associated with Keshan disease, characterized by cardiomyopathy? a. iodine b. zinc c. selenium d. molybdenum

c. selenium Selenium deficiency occurs primarily in selected regions of the world such as China, central Africa, and parts of Europe. The deficiency is linked to Keshan disease and Kashin-Beck disease. Keshan disease is characterized by cardiomyopathy involving cardiogenic shock, congestive heart failure, or both, along with multifocal necrosis of heart tissue, which becomes replaced with fibrous tissue.

Which of the following dietary substances inhibits uptake of non-heme iron? a. ascorbic acid b. lactic acid c. tea d. MFP

c. tea - polyphenols such as tannin derivatives of gallic acid, chlorogenic acids, monomeric flavinoids, and poly- phenolic polymerization products (found in tea and coffee) - oxalic acid (found in spinach, chard, berries, choco- late, and tea, among other sources) - phytic acid, also referred to as phytate, inositol hexa- phosphate, or polyphosphate (found in maize, whole grains, legumes) - phosvitin, a protein containing phosphorylated serine residues (found in egg yolks) - divalent cations such as calcium, zinc, and manganese

The enzyme that converts retinol to retinal and ethanol to acetyl-aldehyde contains 4 ____ atoms. a. copper b. iodine c. zinc d. iron

c. zinc

What genetic disorder causes copper toxicity? a. hemochromatosis b. Keshan disease c. Menkes disease d. Wilson's disease

d. Wilson's disease Wilson's disease, a genetic disorder resulting from a mutation(s) in the gene coding for ATP7B, is characterized by copper toxicity. The incidence of the condition is about 1 in 30,000 live births.

The protein that plays a dual function in both iron and copper homeostasis is: a. ferritin. b. transferrin. c. metallothionein. d. ceruloplasmin.

d. ceruloplasmin. Oxidation of the iron by ceruloplasmin is also required as the iron is transported out of the cell by ferroportin; as stated previously, this oxidation of iron enables iron transport in the blood by transferrin. Ceruloplasmin is released into the blood from the liver and constitutes about 60% to 70% of circulating copper in the blood; the remainder circulates loosely bound to albumin and α-2 macroglobulin for delivery to tissues. Plasma ceruloplasmin concentrations typically range from about 20 to 50 mg/dL; serum copper concentrations normally range from about 70 to 150 μg/dL (10-24 μmol/L).

Nutrient-drug interactions caused by diuretics used to treat high blood pressure are most likely to result in: a. poor absorption of vitamins. b. poor absorption of the drug when taken with grapefruit. c. enhanced metabolism of the drug rendering it less effective when taken on an empty stomach. d. enhanced excretion of potassium and other electrolytes.

d. enhanced excretion of potassium and other electrolytes.

The addition to the diet of which food will alleviate the problem of endemic goiter? a. cabbage b. broccoli c. cassava d. iodized salt

d. iodized salt That some natural foods are goitrogenic was evidenced many years ago when it was discovered that rabbits fed a fresh cabbage diet developed goiters that could be reversed by iodine supplementation. It was later shown that cruciferous vegetables, including cabbage, kale, cauliflower, broccoli, rutabaga, turnips, Brussels sprouts, and mustard greens, contain glucosinolates, which compete with iodide for uptake into the thyroid gland. Perhaps the only food to be identified directly with goiter etiology is cassava, which is consumed in large quantities in many developing countries. Cassava contains the cyanogenic glucoside linamarin that later became known as goitrin

Which mineral facilitates transfer of electrons in the electron transport chain? a. calcium b. nickel c. zinc d. iron

d. iron Heme-containing cytochromes in the electron transport chain, such as cytochromes b and c, pass along single electrons. The transfer of electrons along the chain is made possible by the change in the oxidation state of iron. In the reduced cytochromes, the iron atom is in the ferrous state. The iron atom of the reduced cytochrome becomes oxidized to the ferric state when a single electron is transferred to the next cytochrome. The iron atom of the cytochrome receiving the electron then becomes reduced.

Hemoglobin and hematocrit are common measurements for assessment of nutriture for which mineral? a. iodine b. zinc c. chromium d. iron

d. iron Numerous measurements are used to assess iron nutri- ture. The most common indices are hemoglobin (amount of iron-containing protein found in red blood cells per unit, usually deciliter or liter, of blood) and hematocrit (that proportion of the total blood volume that is red blood cells). However, although these indices indicate the presence of anemia, they are among the last to change as iron deficiency develops.

Which of the microminerals is considered essential for normal brain function? a. chromium b. fluorine c. vanadium d. manganese

d. manganese

A key enzyme in liver urea production requires four _____ atoms per molecule. a. iron b. copper c. zinc d. manganese

d. manganese Arginase, a hydrolase that requires four manganese atoms per molecule, is a cytosolic enzyme responsible for urea formation. The enzyme is found in high concentrations in the liver, the site of the urea cycle. The enzyme cleaves arginine to generate urea and ornithine. Low-manganese diets in animals have been shown to decrease arginase activity.

Which trace mineral is important for activating a key enzyme in gluconeogenesis? a. iron b. copper c. iodine d. manganese

d. manganese Phosphoenolpyruvate carboxykinase (PEPCK), a lyase activated by manganese, converts oxaloacetate to phos- phoenolpyruvate and carbon dioxide. This reaction is important in gluconeogenesis. The activity of phosphoenolpyruvate carboxykinase decreases in animals with manganese deficiency.

What is important in antioxidant DEFENSE? a. iron b. superoxide dismutase (SOD) c. glutathione d. more than one of these e. all three of these

d. more than one of these

Which of the following dietary components impedes copper absorption? a. gluconate b. phosphate c. citric acid d. phytic acid

d. phytic acid

Which micromineral is necessary for iodine metabolism? a. fluorine b. manganese c. chromium d. selenium

d. selenium Selenium is also necessary for iodine metabolism and may regulate thyroid hormone production. The thyroid gland contains several selenoproteins including selenoprotein P, glutathione peroxidase, thioredoxin reductase, and iodothyronine 5′ deiodinase . Iodo- thyronine 5′-deiodinases are selenocysteine-containing enzymes with the selenocysteine present at the active site.