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Other Minerals

Zn, Cu, Cr, I, Mn, Mo

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Zinc

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  • —Found in body mainly as Zn2+

  • —In food bound to proteins and nucleic acids

  • —Heat treatment can cause zinc to form complexes that resist hydrolysis

  • —Malliard browning inhibiting zinc absorption

Zn Digestion and Absorption

  • —Digestion

    • —Needs to be hydrolyzed from proteins and nucleic acids by HCl, proteases, nucleases

  • —Absorption

    • —Mainly at proximal small intestine

    • —2 mechanisms

      • —Carrier mediated (ZIP 4)

      • —Diffusion at high intake

    • —Wide range: 20-60%

    • —Low intakes absorbed more efficiently

    • inhibitors

      • —Antacids

      • —Zantac

      • —Phytate

      • —Oxalate

      • —Polyphenols

      • —Fibers

      • —Fe2+, Cu2+, Ca2+

        • compete for binding receptor sites​

  • enhancers

    • —Citric acid

    • —Picolinic acid (from tryptophan)

    • —Certain amino acids (histidine, cysteine, lysine)

    • —Low Zn status

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Zn Transport and Storage

  • —Zinc transport

    • —In blood bound to albumin --> liver

    • —After liver, transported on albumin and other plasma proteins—globulins, transferrin

  • —Storage

    • —Found in all tissues, esp.

    • —Liver, kidney, muscle, skin, bones

    • —Also in soft tissues: muscle, brain ,heart, lung

    • —Soft tissue Zn doesn’t equilibrate with other Zn pools to release Zn if intake low

  • —Plasma Zn-containing enzymes and metallothionein provide Zn when intake low 

How does Zn Interact with Other Nutrients?

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  • —Vitamin A: Zn is required for alcohol dehydrogenase that converts retinol to retinal, and RBP

    • —low Zn --> decreased vitamin A mobilization from liver

  • —­high Zn    -->   decreased Cu absorption

  • —high­ Zn    -->   decreased Ca absorption

  • —Cadmium  --> decreased Zn function

  • —Folate digestion requires a Zn-dependent hydrolase

  • —Lead may replace Zn in an enzyme necessary for heme synthesis

study question

  • why does high Zn decreased Cu and Ca absorption?

Zn Functions

  • —Catalytic role

    • —Zinc is a component of many metalloenzymes

  • —Structural role

    • —Zinc finger motif helps stabilize protein structure

    • —Zinc also help maintain membrane structure

  • —Regulatory role

    • —Zinc finger proteins modulate gene expression

    • —Zinc also affects release of certain hormones

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Zn Deficiency

  • —RDA has been established

  • —Risk factors

    • —Fast growth and pregnancy

    • —Alcoholism

    • —Chronic diseases, stress, trauma, surgery

    • —Malabsorption eg in Celiac Disease

  • —Varies symptoms includes

    • —Dermatitis

    • —Retarded growth in children

    • —Delayed sex maturation in children

    • —Pica

Zn Toxicity

  • —Chronic high Zn intakes can lead to copper deficiency

  • —Acute toxicity

    • —Nausea, vomiting, bloody diarrhea,

    • —Abdominal cramps

    • —Weakness

    • Sweating

Copper

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  • Present as cuprous (Cu+) or cupric (Cu2+)

  • Richest in organ meat and shellfish

  • Some plant food is rich in copper

Cu Digestion and Absorption

  • —Cu+ and Cu2+ bind to organic compounds esp protein in food

  • —Need to be freed by HCl and pepsin in stomach and proteolytic enzymes in small intestine

  • —Can be absorbed in the stomach, but small intestine is the main site

  • —Like some other minerals

    • —Active transport (saturable carrier): DMT1

    • —Passive diffusion when concentrations high

    • inhibitors​

      • —Phytate

      • —Some minerals

      • —Zn, Fe, Ca, Mo, P

      • —Antacids: neutralize HCl

      • Vitamin C

  • enhancers​

    • —Amino acids, esp. histidine, methionine, cysteine

    • —Acids: citrate,  lactate, acetate, etc

Cu Transport and Storage

  • —<150 mg Cu stored in the body

    • —Mainly in liver, brain, and kidneys

    • —Within cells, Cu binds to amino acids, proteins, and chaperones

    • —Ceruloplasmin released from the liver is the major form of Cu in circulation

    • —Cu can also bind to other plasma protein such as albumin

Cu Functions

  • Iron Metabolsim

    • ​—Ceruloplamin transports Cu in blood, and also serves as an oxidase and an antioxidant

    • This reaction is what coverts Fe to the form that can bind to transferrin

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  • Antioxidant function

    • —Extracellular and cytosolic superoxide dismutase (SOD) is Cu- and Zn-dependent

  • Energy metabolism

    • —Cytochrome C oxidase contains Cu and functions in the terminal step of respiratory chain, transferring electrons to molecule oxygen to form water. This is critical for ATP synthesis in the mitochondria

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Cu Deficiency

  • —RDA has been established

  • —Risk factors

  • —Infants fed only cow milk which is low in Cu

    • —Premature infants

    • —Malabsorption

  • —Hypochromic anemia that does not respond to iron supplement

    • —Anemia caused by impaired Fe mobilization due to low ceruloplasmin level

Cu Toxicity

  • —UL has been established

  • —Rare in the US

  • —Symptoms include abdominal pain, nausea, vomiting, and diarrhea

  • —Wilson’s Disease (a genetic disorder)

    • —Cu accumulates in liver, kidneys, and brain

    • —Causes tissue damage

Chromium

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  • A metal element that exists in several oxidation states

  • Cr2- to Cr6+

  • Cr3+ most stable- probably most important in human body

  • —Food sources

    • —Brewer’s yeast

    • —Tea, beer, wine

    • —Meats (esp. organs), grains, cheese, mushrooms

    • —Apple, banana, orange and grape juices

    • —Spices (cinnamon, cloves, bay leaves, etc)

    • —Content affected by food processing and refining

Cr Absorption

  • —Absorption: exact mechanism unclear

    • —Organic form (eg. in Brewer’s yeast) is better absorbed

  • —Absorption enhanced by:

    • —Amino acids (methionine, histidine, phenylalanine)

    • —Vitamin C

  • —Absorption inhibited by

    • —Antacids

    • —Phytate

Cr Transportation and Storage

  • —Transported in blood bound to transferrin and albumin

    • —Large intakes may affect iron binding capacity

  • —Storage: thought to be stored with ferric iron because of its transport by transferrin.

    • —Tissues high in Cr:

      • —Kidney, Liver, Muscle, Spleen, Heart, Pancreas, Bone

Cr Functions

  • —Glucose Tolerance factor (GTF)

    • —Organic complex of Cr3+  

    • —Insulin more effective in the presence of Cr

    • —Insulin binding to insulin receptor seems to bring more Cr into cell

    • —Cr affects kinase activity that influences IR

    • —Cr signals the translocation of GLUT4 to cell surface to enhance uptake of glc from blood

      • —Muscle

      • Adipocytes

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study question

  • explain the relationship between Cr and insulin receptors

Cr Deficiency

  • —AI has been established

  • —Risk factors

    • —Total parenteral nutrition

    • —Increased needs: stress, trauma, intense exercise

    • —Diseases such as diabetes and heart disease

  • —Signs and symptoms

    • —Weight loss

    • —Peripheral neuropathy

    • —Insulin resistance

Cr Toxicity

  • —Cr6+ is a known carcinogen for lung cancer if inhaled

  • —Cr3+  appear to be safe

  • —No UL has been established due to lack of evidence

  • —“Use with caution”

Iodine

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  • Non-metal element

  • Functions in its ionic form, iodide I-

  • Iodine contents in plants and animal products reflect Iodine level in the soil

  • Seafood is rich source

    • Including sea weeds

I Absorption

  • —Rapid, complete absorption throughout the whole GI

  • —Iodide absorbed more efficiently

  • —The thyroid hormones (T3 and T4) can be absorbed unchanged

I Functions

  • —Iodide is distributed in all tissues

  • —Thyroid gland contains 70% of total iodide

    • —Sodium-dependent active transport

  • —Thyroid gland uses iodine to synthesize thyroid hormones

    • —Thyroxine (T4)

    • —Triiodothyronine (T3)

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I Deficiency

  • —RDA has been established

  • —Risk factors

    • —Living in regions where soil is deficiency in iodine

    • —Increased requirements (eg pregnancy, lactation)

    • —Goitrogens: compounds that interfere with iodine metabolism

  • Goiter, Cretinism, Hypothyroidism

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  • —Goiter

    • —I deficiency -->  I depletion in thyroid --> Decreased plasma T4 levels --> Increased TSH level --> Hyperplasia of thyroid gland

    • Thyroid gland can return to normal size if adequate I intake is restored

  • —Cretinism

    • —Affect fetus

    • —Retarded mental development

    • —Retarded physical growth

    • —Deaf mutism

    • —Muscular rigidity

  • —Hypothyroidism

    • —Fatigue

    • —Edema ( --> weight gain)

    • —Lassitude (lack of energy)

      • —Cold intolerance

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I Toxicity

  • —UL has been established

  • —Acute toxicity

    • —Nausea, vomiting

    • —Burning of throat and the mouth

    • —Diarrhea

    • —Fever

  • —Excessive iodine

    • —Can cause hyperthyroidism in individuals with chronic deficiency

    • —Can cause hypothyroidism in iodine sufficient people

Manganese

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  • In body exists at Mn2+ or Mn3+ 

  • Good sources include

    • Whole-grain cereals

      • Differs by plants

      • Processing affect Mn contents

    • Dried fruits and nuts

    • Leafy vegetables

Mn Absorption

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  • —Limited information on Mn absorption

  • —Absorption rate is low an varies, often <5%

  • —Mn in tea is not well absorbed

  • —Women absorb more than men

  • —Mn from MnCl2 is absorbed more efficiently than Mn from plant foods

  • —Thought to be absorbed as divalent ion, Mn2+

  • —May involve DMT1

  • —The same transporter needed for iron absorption

    • inhibitors​​

      • —Histidine

      • —Citrate

  • enhancers​

    • —Fiber

    • —Oxalate

    • —Phytate

    • —Iron, zinc, calcium

      • All three can form divalent ion, competing for DMT1

Mn Transport and Storage

  • —Mn2+  can be free in blood or bind to plasma proteins such as albumin and globulins

  • —Mn3+ Can bind to transferrin

    • —Another site to compete with Fe

  • —Rapidly cleared from blood and accumulates mainly in mitochondria

  • —Found in most tissues/organs

    • Highest in bone, liver, pancreas, and kidneys

Mn Functions

  • —At the molecular level, Mn, like other trace elements, can function both as an enzyme activator and as a constituent of metalloenzymes

  • —Mn binds to substrate or enzyme directly, inducing conformational changes.

    • —Enzymes from nearly all classes can be activated by Mn in this manner

    • —Activation of most of these enzymes, however, are not Mn specific; therefore, not affected by Mn deficiency

Mn Deficiency

  • —Generally does not develop in human unless deliberately eliminated from the diet

  • —Associated with striking and diverse physiological malfunctions

  • ​Low levels of Mn is observed in certain chronic diseases. Studies indicate that Mn insufficiency might contribute to certain diseases.

  • —Symptoms

    • —Nausea and vomiting

    • —Dermatitis

    • —Decreased growth of hair and nails

    • —Poor bone formation and skeletal defects

    • —Loss of equilibrium and neonatal ataxia

    • —Altered carbohydrate and lipid metabolism

Mn Toxicity

  • —Accumulation in brain leads to neurological abnormalities

  • —Can occur in people with liver failure

    • —Mn is excreted mainly via bile in the feces

  • —In neonates on total parenteral nutrition

    • —Lack of absorption control because nutrients are delivered to blood directly

  • —Inhalation leads to Parkinsonism-like symptoms

    • —High risk for certain professions, eg welders, workers at military factory factories (many weapon systems require Mn)

  • —AI and UL have been established​

Molybdenum

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  • A metal element that is primarily found as Mo4+ and Mo6+

  • Widespread among foods

    • True to many minerals, the levels in food are determined directly (in plants) or indirectly (in animal products) by the level in the soil.

  • Good sources: legumes, meats, fish, poultry, grains

  • Dairy and fruits are low in Mo

Mo Absorption, Transport and Storage

  • —Molybdate in foods does not appear to need digestion

  • —Absorption

    • —Absorption rate relatively high, 50~90%

  • —In blood, Mo bound to proteins (such as albumin) as molybdate

  • —Low tissue concentration

    • —Main storage sites: liver, kidneys, bone

Mo Functions

  • —Biological role of Mo centers around the redox function of the element

  • —The biological form of molybdenum, present in almost all molybdenum-containing enzymes (molybdoenzymes), is an organic molecule known as the molybdenum cofactor.

  • —Mo cofactor is needed by three enzymes in human body

    • —Sulfite oxidase

      • —catalyzes the final step in the metabolism of methionine and cysteine

    • —Xanthine Dehydrogenese and Xanthine Oxidase

      • —Catalyzes breakdown of DNA and RNA to form uric acid, contributing to anti-oxidant capacity in blood

    • —Aldehyde oxdiase

      • —Very similar to xanthine oxidase

Mo Deficiency

  • —RDA has been established

  • —Rare unless diet is rich in copper, sulfite, or tungstate

  • —Low Mo intakes have been associated with esophageal cancer in China

    • —Mainly squamous cell cancer

  • —Signs

    • —Low blood uric acid

    • —High blood methionine, hypoxanthine, and xanthine

Mn Toxicity

  • —Relatively nontoxic

  • —Seen in people living in area with high Mo level in the soil or with high occupational Mo exposure

  • —Signs: increased blood uric acid levels è Gout

  • —UL has been established

©2023 by Syracuse University Dr.Margaret Voss

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