TRACE MINERALS ( Zinc, Selenium, Boron and Cobalt)Ms. Latika Yadav (Research Scholar), Dept. of Foods and Nutrition, College of H.Sc,Maharana Pratap University of Agriculture and Technology, MPUAT, Udaipur, rajasthan-313001, email.id: firstname.lastname@example.org
MICRO NUTRIENTSMicronutrients are nutrients required by humans and other livingthings throughout life in small quantities to orchestrate a wholerange of physiological functions, but which the organism itselfcannot produce. For people, they include dietary trace minerals inamounts generally less than 100 milligrams/day as opposed tomacrominerals which are required in larger quantities.The microminerals or trace elements include at least iron, cobalt,chromium, copper, iodine, manganese, selenium, zinc andmolybdenum.Micro nutrient elements or trace elements, are present lessthan0.005% (50ppm) of the body weight. It is essential that the term“trace” not be interpreted to mean “unimportant”.
Micronutrients are generally divided into 2 groups:1) Trace minerals: that includes Iron, Copper, and Zinc.2) Ultra trace minerals :includes Chromium, Manganese, Flouride, Iodide, Cobalt, selenium, Silicon, Arsenic, Boron, Vanadium, Nickel, Cadmium, Lithium, Lead and Molybdenum.Minerals explained in my presentation are:1) Zinc2) Selenium3) Copper and4) Boron.
1. ZINCOverview:• 30th element in the periodic table (IIB element) – MW = 65.37, completely filled d orbitals• In aqueous solutions – One oxidation state, namely Zn2+ – Prefers tetrahedral complex formation• Not a redox active metal – readily complexes with amino acids, peptides, proteins and nucleotides – affinity for thiols, hydroxy groups & ligands with electron-rich nitrogen donors• Approximately 300 enzymes are associated with zinc• Biological functions of Zn are divided into three categories – Catalytic, Structural, Regulatory
FUNCTIONS OF ZINC1.) Zinc-containing enzymes : serving as an essential cofactor •More than 70 enzymes •Secondary & tertiary protein structures •Metal stabilized active sites •Examples of general types of enzymes requiring Zn as cofactor: Dehydrogenases Anhydrase Polymerases dismutases phosphatases peptidases kinases deaminases
2. Zn: Nuclear transcription factors (>130) •Same protein structural role forms “zinc-fingers” •“Zn-fingers” bind DNA •allow different nuclear hormones to interact with DNA via different DNA binding proteins •up to 37 “fingers” have been found on a single transcription factor •Vit. A, Vit. D, steroid hormones, insulin-like growth factor-1, growth hormone, and others bind to zinc-finger proteins to modulate gene expression. •Zn is responsible for thymidine incorporation3. Cu/Zn Superoxide Dismutase General class of enzymes that protect against oxidative damage in the body.4. Insulin Zn important structurally Zn needed for insulin “stored” in pancreas Functionality drops rapidly so more of a “working store” than a static store
Transcription Factors• Transcription factors – Regulate gene expression – Involved in virtually all biological processes: • Development, differentiation, cell proliferation, response to external stimuli – Consists of 2 domains • DNA Binding Domain (DBD) – recognizes and binds to specific DNA sequence elements in the promoter of target genes • Protein-interacting Trans activation Domain (TAD) – influences the rate of transcription.• Revelation – Gene expression is controlled by specific proteins call transcription factors • Zinc containing transcription factors account for 1% of genome – Zinc plays key structural role in transcription factor proteins – Ligands for transcription factors include: • Vitamin A • Vitamin D • Bile acids • Thyroid hormones
Zinc Finger Proteins• Zinc finger proteins are characterized by their utilization of zinc ions as structural components• C2H2 zinc finger binding motif – Predominant motif in eukaryotic transcription – Involved in skeletal differentiation – Zinc binding motif is determined by the Zinc-finger presence of 2 cysteine and 2 histidine Interacting with DNA residues that engage in a four coordinate bond with a singe Zn ion – Bind to response elements in the upstream promoters of genes transcribed by RNA poly 2 – Binds to 5S ribosomal RNA gene, and 5S RNA, and activates transcription by RNA polymerase 3.
Membrane Stability• Membrane fractions contain high concentrations of Zn – Increases rigidity of cell• Protection from oxidative damage – Competition for binding sites with redox metalsMembrane FunctionIn deficient animals: – Failure of platelet aggregation • Due to impaired Calcium uptake – Peripheral neuropathy • Brain synaptic vesicles exhibit impaired calcium uptake – Increased osmotic fragility in RBCs • Decreased plasma membrane sulfhydryl concentration Immune Function• After Zinc depletion – All functions within monocytes were impaired – Cytotoxicity decreased in Natural Killer Cells – Phagocytosis is reduced in neutrophils – Normal function of T-cells are impaired – B cells undergo apoptosis• High Zn supplementation shows alterations in cells similar to Zn depletion
Whole Body Fluxes Plasma/Serum 2.4 mg Target tissues Diet Zn++ a-2 macroglobulin Including 4-15 mg/da (30%) Liver (~0.15 mM) albumin 1.2 g (60%) IntestineZn++ (50-100mM) Milk: 2-3 ug/mL 1-2 mg/da Pancreatic & Metallothionine Biliary Other Losses: Excretion: Sweat, Skin, Hair up to Chelating Agents 1 mg/da Phytates 4-5 mg/da Seminal Fluid: 196 ug/mL Menstrual Loss: 0.1-0.5 mg Feces: 3-14 mg/da Urine: 0.4-0.6 mg/da
Absorption• Absorption takes place throughout the intestine – Primarily in the jejunum – Some absorption in the rumen – No measurable amounts absorbed from stomach cecum or colon• In small intestine – Nonmediated (nonsaturable) process • Not affected by dietary Zn intake – Mediated (saturable) process • Stimulated by Zn depletion
Dietary Factors that Affect Zn Absorption• Feed/Food source • Presence/Absence of other divalent cations• Phytate (calcium-phytate-zinc – Fe, Ca complex) • Efficiency of absorption can vary – Mainly hexa- and from 15-60% pentaphosphate derivatives – Under normal conditions 1/3 of – Highly dependent on calcium dietary Zn is absorbed – Zn status alters efficiency of• Amino Acids absorption – histidine, cysteine • Uptake and retention is > in growing animals
Transport in blood• Plasma contains approx .1% of the total zinc of the body• Albumin is major portal carrier• Binds to albumin by tetrahedral ligation to sulfur atoms – 70% of Zn is bound to albumin in plasma – 20-30% bound to α-2 macroglobulin – Other plasma proteins • Transferrin, histidine-rich glycoprotein, metallothionine• Plasma Zn concn’s respond to external stimuli – Intake fluctuations – Fasting – Acute stresses • infection• Plasma Zn levels do not influence absorption from mucosa• Most reductions in plasma levels reflect increased hepatic uptake – Hormonal control
Excretion• Lost via hair, sweat, desquamation, bile pancreatic secretions, seminal fluid, urine, feces• Main endogenous loss – Secretions into gut • Bile and pancreas – Mucosal cells• Urinary and integumental losses • < 20% under normal conditions – Losses increase with trauma, muscle catabolism, and administration of chelating agents (EDTA)• Primarily in fecal material – Unabsorbed Zn – Secreted Zn (endogenous sources) • From pancreatic and intestinal
Regulation• Metallothionein – Concentrated in liver, kidney, pancreas, intestine – Acts as a Zn2+ buffer • Controls free Zn2+ level • Control intracellular Zn pool responsive to both hormones and diet• Zn-binding protein, metallothionein (MT), is involved in the regulation of Zn metabolism• MT is inducible by dietary Zn via the metal response element (MRE) and MTF-1 mechanism of transcriptional regulation – ↑ in cellular MT ↑ Zn binding within cells• Acute infections associated with proinflammatory cytokines increses Zn uptake into liver, bone marrow and thymus and reduces the amount going to bone, skin and intestine
Storage• Storage sites – No specfic storage sites are recognized • Within cells, amounts sequestered within metallothionine could be considered as stores • Anorexia, muscle catabolism, tissue zinc release – Metalloenzymes cling tenaciously to zinc – Serum/plasma zinc drops rapidly (~1 week) with zinc deficient diet • Zinc turnover is extensive and rapid – Two-components of turnover, fast ~12.3 days, and slow, ~300 days • Fast pool is also called the “exchangeable” pool – Usually amounts to 157-183 mg Zn
Interactions• Copper: - High Zn diets reduce Cu absorption • electronic configuration competition – Metallothionine synthesis induced • sequesters Cu in mucosal cell preventing serosal transfer – Happens with 150mg Zn for two years – Can be used with Wilson’s disease patients – High copper diets do not interfere with Zinc absorption• Iron: Supplements inhibit zinc absorption • Ferrous > Ferric, heme no effect • Pregnant and taking >60mg Fe/day should also take Zn• Calcium: High Ca diets reduce Zn absorption • effect enhanced in phytate rich diets • not sure how much of a problem in humans – post menopausal women yes, adolescent girls, no• Other: – Tin (Sb), not usually high in diet, but diets high in Tin can increase fecal Zn excretion – Cadmium (Cd), alter Zn distribution in body rather than altering absorption – Folic acid, conjugase requires Zn • High doses sometimes impair Zn status further in low Zn situation - mechanism currently unclear
Mechanisms of Toxicity• Excess accumulation within cells may disrupt functions of biological molecules – Protein, enzymes, DNA • Leads to toxic consequences• Anemia – Impaired copper availability• Acute excessive intakes – Local irritant to tissues and membranes • GI distress, nausea, vomiting, abdominal cramps, diarrhea• Relatively non-toxic – Sources of exposure – drinking water, feed, polluted air
Deficiency• Signs • More signs – Growth retardation – Night blindness – Delayed sexual maturation & impotence – Impaired taste (hypoguesia) • Impaired testicular development – Delayed healing of wounds, burns, – Hypogonadism & hypospermia decubitus ulcers – Alopecia – Impaired appetite & food intake – Acroorifical skin lesions – Eye lesions including photophobia • Other, glossitis, alopecia & nail & lack of dark adaptation dystrophy – Immune deficiencies – Behavioral changes
Sources• Relatively abundant mineral – Good sources: shellfish, beef and other red meats – Slightly less good: Whole-grains – most in bran and germ portions • 80% lost to milling • phytates, hexa & penta phosphates depress absorption – P/Zn ratios of 10 or more – Relatively good sources: nuts and legumes• Eggs, milk, poultry & fish diets lower than pork, beef, lamb diets – High meat diets enhance absorption • 280g or 10 oz fits right into food pyramid guide • cys & met form stable chelate complexes
2. SELENIUM•Selenium as a metal was first reported by Berzelius in 1817 and occurin nature in variety of forms and colours.•Selenium is frequently found in combination with lead, copper,mercury and silver. These combinations are called selenides.•Selenium is an allotropic metal in group 6 of the fourth period of theperiodic table. Its molecular weight is 78.96 Da and its atomic weight is34.•Selenium has 26 isotopic forms, only 5 of these are naturally occuring:Se76,Se78,Se77,Se80,Se82.Of the radioisotopes.•Se and Vit.E both play important roles in the detoxification of peroxideand free radicals.
FUNCTIONS OF SELENIUM:1. Component of glutathione peroxidase • catalyzes removal of hydrogen peroxideGSH + H2O2 GSSG + H2OGSH = reduced glutathioneGSSG = oxidized glutathione2. Component of iodothyronine-5’- deiodinase • Converts T4 to T33. Improves killing ability of neutrophils • Reduces the prevalence and severity of mastitis4.Protects cells from auto oxidative damageShares this role with vitamin E 5.) Important antioxidant
Relationship of glutathione peroxidase,selenium, and vitamin E GSH peroxidase contains selenocysteine
Selenoproteins: Enzyme Activities1. At least 25 selenoproteins have been identified in human biochemistry.2. Glutathione peroxidase (GPx) has been the functional parameter used for the assessment of Se status. GPxs catalyze the reduction of peroxides that can cause cellular damage.3. Thioredoxin reductase (Trx R) provides reducing power for several biochemical processes and defends against oxidative stress.4. Selenoprotein P, the majority of the Se found in the bloodstream, acts as an antioxidant enzyme.5. Selenoprotein W may play a role in oxidant defense.6. The peroxiredoxins (Trx PX) define an emerging family of peroxidases able to reduce hydrogen peroxide and alkyl hydroperoxides.7. Selenophosphate synthetase is an enzyme required for the incorporation of selenocysteine into selenoproteins.
ABSORPTION, METABOLISM AND EXCRETIONAbsorption is very efficient , with most of the ingested selenium absorbedreadily from a variety of food stuffs. The source of the mineral can haveeffects on its absorption.Se is transported from the gut on the VLDL and LDL : Red cells, liver,spleen, muscles, nails, hair and tooth enamel all contain significantquantities of the mineral.DAILY SELINIUM FLUX IN A 70 KG MAN Sweat, skin loss ~ 80 μ g/day Diet 6- Plasma VLDL,or LDL, 0.5-2.0g/ml Feces ~ 50 200μg/day μ g/day (50-200 μ g/L) Urine~ 50 μ g/day Selenoproteins in tissues
Food Sources Food content tends to follow Se content of soil – richest food sources are organ meats and sea foods, followed by cereals and grains, dairy products, fruits and vegetables Se content of grains can vary by 10,000 fold• Requirements determined based on serum glutathione peroxidase activity.• The NAS-NRC has recommended that an intake no less than 50 and no mare than 200g/day should be sufficient to meet need of average adult. Selenium Deficiency Diseases• Major problem in livestock• Human deficiency is rare except in areas with low Se content in soil Keshan disease occurs in Keshan China: endemic cardiomyopathy and muscle weakness (due to oxidized lipids) Aggressive supplementation has eliminated disease• Iatrogenic deficiency TPN without supplemental Se
Selenium Toxicity• Range of dietary Se intake without toxicity is narrow• Acute selenium poisoning can result in cardiorespiratory collapse• Chronic toxicity (selenosis) changes in nail structure and loss of hair• Hair and nail brittleness• Se toxicity in farm animals is characterized by Hoof loss and a neuromascular condition known as “Blind Staggers”.
Selenium and Cancer Prevention• Epidemiologic evidence indicates low intakes of Se are associated with higher risk of prostate cancer• Prospective study of Se supplementation demonstrated 42% reduction in cancer incidence• Small sample size and other confounding factors have diminished enthusiasm for the results of these studies.• In 1977, Gerhard Schrauzer and his team reported that Se is a potential human cancer-protective agent.• Later human epidemiological studies indicate a statistically significant inverse relationship between Se level and risk of cancer overall, particularly in men. Moreover, clinical trials showed that supplemental Se reduced the incidence and mortality of several types of human cancers.• In the 1980s, the birth of synthetic organoselenium derivatives as cancer chemopreventive agents in laboratory rodents was reported by Karam El- Bayoumy.• Currently two clinical invention trials in the U.S. (Selenium and Vitamin E Cancer Prevention Trial, SELECT), Phase III, and in Europe (Prevention of Cancers by Intervention with Selenium, PRECISE) are in progress.
3. BORON•Boron is the chemical element with atomic number 5 and thechemical symbol B. Because boron is produced entirely by cosmic rayspallation and not by stellar nucleosynthesis, it is a low-abundanceelement in both the solar system and the Earths crust. However, boronis concentrated on Earth by the water-solubility of its more commonnaturally occurring compounds, the borate minerals. These are minedindustrially as evaporate ores, such as borax and kernite.•Boron was shown to be an essential element for plants early thiscentury and there is now evidence that it is also necessary for humans.Boron is distributed throughout the human body with the highestconcentration in the bones and dental enamel.•Prior to 1981, boron was not considered an essential nutrient; boronwas first shown to be an essential mineral for growing chicks. It wasnot until 1990 that boron was accepted as an essential nutrient forhumans.
FUNCTIONS OF BORON:• Boron seems to be essential for healthy bone and joint function, possibly via effects on the balance and absorption of calcium, magnesium and phosphorus. It seems to affect cell membranes and the way signals are transmitted across these membranes.• Boron affects the metabolism of steroid hormones and may also play a role in converting vitamin D to its more active form, thus increasing calcium uptake and deposition into bone. Boron also increases male sex hormone levels.• Boron is required for the maintenance of bone and normal blood levels of estrogen and testosterone; within eight days of supplementing boron women lost 40 percent less calcium, 33 percent less magnesium and less phosphorus through their urine.1. Through reactions with certain bio substances to maintain proper cell membrane function or stability and influences hormone reception and transmembrane signaling.
Absorption and metabolismBoron is efficiently absorbed and excreted in the urine.Deficiency•Boron deficiency seems to affect calcium and magnesium metabolism, and affectsthe composition, structure and strength of bone, leading to changes similar to thoseseen in osteoporosis.•This is likely to be due to decreased absorption and increased excretion of calciumand magnesium.•Boron deficiency combined with magnesium deficiency appears especiallydamaging in cases of osteoporosis. Due to its effects on calcium and magnesiummetabolism, boron deficiency may also contribute to the formation of kidneystones. Boron deficiency also seems to decrease mental alertness.•There may also be a link between boron deficiency and osteoarthritis.
Dietary need and sourcesHuman requirement of Boron most likely between 0.5 and 1.0 mg/day; rich foodsources include noncitrus fruits, leafy vegetables, nuts, pulses and legumes.Boron toxicologyToxic effects appear at intakes of about 100 mg. The World Health Organizationhas banned boron (in the form of boric acid) as a food additive and preservative.Toxic effects include a red rash with weeping skin, vomiting, diarrheacharacterized by a blue green color, depressed blood circulation, coma andconvulsions. A fatal dose in adults is 15 to 20 g and in children 3 to 6 g. Repeatedintakes of small amounts can cause accumulative toxicity. Signs of toxicity includenausea, vomiting, diarrhea, dermatitis, and lethargy. In addition, excess boronintake induces riboflavinuria. Landauer found that boron-induced teratogenicproblems include skeletal abnormalities and were reduced with riboflavin therapy.
SupplementsSodium borate is the most common form of supplement.Boron is increasingly used in calcium and bone-replenishing nutritional formulas. It may be particularlyuseful in those whose magnesium intake is low. Thiseffect may be useful in the prevention of kidney stones.Because of its effect on testosterone levels, boronsupplements have been marketed to athletes on thebasis of their ability to increase muscle mass andstrength. A 1994 study of the effects on ten malebodybuilders did not find any increases in those withboron supplements.
Therapeutic uses of supplementsBoron may be beneficial in the treatment of osteoporosis.Supplements of around 3 mg per day have been shown toenhance the effects of estrogen in postmenopausal women.This is likely to contribute to its beneficial effects on bonehealth.Studies done in 1994 on athletic college women suggest thatboron supplements decrease blood phosphorus concentrationand increase magnesium concentration. Both of thesechanges are beneficial to bone-building.Because of its sexhormone-enhancing effects, boron may help to protect againstatherosclerosis.OsteoarthritisBoron supplements of 6 to 9 mg per day have been used totreat osteoarthritis with some improvement of symptoms.Boron content in arthritic bones may be lower than that ofnormal bones and extra boron may increase bone hardness.
Interactions with other nutrients•boron is an essential element and that it is involved in regulatingparathormone action. Therefore, it is likely that boron influences themetabolism of calcium, phosphorus, magnesium and cholecalciferol.•Animal studies have indicated that cholecalciferol deficiencyenhances the need for boron, and that boron might interact in somemanner other than through an effect on cholecalciferol metabolism.•The relationship seemed strongest between boron and magnesium,because boron supplementation alleviated magnesium deficiencysigns in chicks. Boron does not seem to consistently alleviate signsof calcium and phosphorus deficiency.•Boron and boron compounds can influence calcium metabolism,and tissue boron level changes in animals with abnormal calciummetabolism. In humans, a low caries incidence has been associatedwith adequate boron levels; however other studies indicated that highlevels of orally administered boron increased dental caries.
4. COBALT:Cobalt is another essential mineral needed in very smallamounts in the diet. It is an integral part of part of vitamin B12,cobalamin, which supports red blood cell production and theformation of myelin nerve coverings. Some authorities do notconsider cobalt to be essential as a separate nutrient, since it isneeded primarily as part of B12, which is itselfessential.Cobalt, as part of vitamin B12, is not easily absorbedfrom the digestive tract. The body level of cobalt normallymeasures 80-300 mcg. It is stored in the red blood cells and theplasma, as well as in the liver, kidney, spleen, and pancreas .Sources: Cobalt is available mainly as part of B12. There issome question as to whether inorganic cobalt is actually usablein the human body. Meat, liver, kidney, clams, oysters, andmilk all contain some cobalt. Ocean fish and sea vegetableshave cobalt, but land vegetables have very little; some cobalt isavailable in legumes, spinach, cabbage, lettuce, beet greens,and figs.
Functions: As part of vitamin B12, cobalt is essential to redblood cell formation and is also helpful to other cells.Uses: Cobalt, as part of B12, is used to prevent anemia,particularly pernicious anemia; vitamin B12 is alsobeneficial in some cases of fatigue, digestive disorders, andneuro-muscular problems. There are no other known usesexcept for the radioactive cobalt-60 used to treat certaincancers.Deficiency and toxicity: Toxicity can occur from excessinorganic cobalt found as a food contaminant. Beer drinkerscardiomyopathy (enlarged heart) and congestive heartfailure have been traced to cobalt introduced into beerduring manufacturing. Increased intake may affect thethyroid or cause overproduction of red blood cells,thickened blood, and increased activity in the bone marrow.
.Requirements: No specific RDA is suggested for cobalt. Our needs arelow, and vitamin B12 usually fulfills them. The average daily intake ofcobalt is about 5-8 mcg. It is not usually given in supplements.Absorption and bioavailability:The extent of gastrointestinal absorption of cobalt depends upon thedose, with very low doses being almost completely absorbed, whereaslarger doses are less well absorbed. Nutritional factors also influenceabsorption, for example, absorption is reduced by amino acids, andincreased in iron deficiency.Distribution and metabolism:In human autopsy studies, the liver (the organ where vitamin B12 isstored) contains the highest concentration of cobalt (approximately 20%of the total body content). In the human body there is no evidence ofaccumulation of cobalt with age.Excretion:Cobalt is mainly excreted in the urine but also in the faeces. Independentof the route of exposure, most cobalt is eliminated rapidly, with a smallproportion being eliminated slowly and having a half-life of the order ofyears.
studies related to cobalt:Human dataSeghizzi et al., 1994A review of the literature from the 1960s described endemics of cardiomyopathywith mortality rates of up to 50 % in heavy consumers of cobalt-fortified beer(containing cobalt concentrations of 1 – 1.5ppm). The intake of cobalt in such consumers was estimated to be 6 – 8 mg daily.Dietary protein deficiency may be an important factor in cobalt inducedcardiomyopathy, and zinc and magnesium deficiency may also play a part.Animal dataPedigo et al., 1988Cobalt chloride was administered to groups of 10 mice in drinking water providing23, 42 or 72 mg cobalt/kg bw/day for up to 13 weeks. The highest dose levelresulted in a dose- and time-dependent decrease in testicular weight anddecreased epididymal sperm concentration, along with decreases in both motilityand percent motile forms of sperm. Fertility was decreased at week 13. There wasa dosedependent decrease in testicular weights (as a ratio to body weight), whilstserum testosterone levels were increased 5 to 7 fold at all dose levels.
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