Lecture 9 - Minerals & Trace Elements

What are the major minerals needed for our bodies?

*All form solid crystals

• Na

• Mg

• P

• S

• Cl

• K

• Ca

What is the importance of minerals in the body?

• Elements needed by the body in small amounts for health and maintenance

• Major elements are needed in the diet in amounts greater than 100mg/day or are present in the body in amounts greater than 0.01%

• Trace minerals are available in unprocessed foods, some processed foods, and dietary supplements

  • Not in pure form, unless in supplement

• Bioavailability is very important

• Upper limits have been established because certain minerals can be toxic if taken in too high an amount

  • Iron

How do minerals act as cofactors for particular enzymes?

• The mineral cofactor combines with the incomplete enzyme to form the active enzyme

• The active enzyme binds to the molecules involved in the chemical reaction and accelerates their transformation into the final product

• The final products are released, while the enzyme remains unchanged

What is calcium as a mineral?

• The most abundant mineral in the body

• Accounts for 1-2% of adult body weight

• 99% of calcium in the body is found in bones and teeth

• 1% found in fluids

  • Nerve transmission, muscle contractions, blood pressure regulation, and hormone release

What is the calcium absorption pathway?

• Calcium bioavailability decreases in the presence of tannins, fibre, phytates, and oxalates

  • In the small intestine, Ca can bind & inhibit; in the large intestine, it binds to bacteria, breaking down SCFAs

  • Ca is reactive to fibre, allowing binding

• Levels of Ca in the blood are tightly regulated by parathyroid hormone and calcitonin

1. Vitamin D turns on the synthesis of calcium transport proteins

2. Calcium transport proteins shuttle calcium across the mucosal cell

3. A calcium pump that requires energy moves calcium from the mucosal cells to the bloodstream

What is the connection between Ca and inulin/acid

• Increased Ca absorption by inulin/acid

• Inulin (a prebiotic fibre promoting colonic bacterial growth) and acid (specifically short-chain fatty acids produced by fermentation) enhance absorption in the large intestine

• Inulin increases the solubility and bioavailability of Ca, boosting bone health and density

What is the pathway of regulation of blood calcium levels?

Low blood Ca →

• Parathyroid glands →

• Parathyroid hormones →

  • Stimulates calcium release from bone →

    • Normal blood calcium

  • Ca reabsorbed by the kidney →

    • Normal blood calcium

  • Activates vitamin D →

    • Increases intestinal Ca absorption →

    • Normal blood calcium

High blood Ca →

• Thyroid gland →

• Calcitonin (osteoblast) →

• Inhibits calcium release from bone →

• Normal blood calcium

What is the pathway of bone remodelling?

1. Activation: Osteocytes detect damage and send signals to the bone surface, causing precursor cells to differentiate into active, mature osteoclasts.

2. Resorption: Osteoclasts attach to the bone matrix, creating a pit that degrades the inorganic and organic components, releasing calcium into the bloodstream.

3. Reversal: Osteoclasts undergo apoptosis. Mononuclear cells clean up the resorption site and signal osteoblasts.

4. Formation: Osteoblasts move into the resorption pit and deposit new, unmineralized matrix called osteoid.

5. Termination/Mineralization: The osteoid is mineralized with calcium and phosphate, becoming hard, new bone, lining the surface.

What is the calcium content of foods?

• In a range of foods

• Highest in milk and alternative products and fish with bones

• Soft drink consumption is affecting the calcium intake of teenagers by replacing milk

• Low calcium intake early in life increases the risk of osteoporosis and increases the number of overweight and obese individuals

What connection is there between sex and bone mass?

• Bone mass in men and women is the same until puberty

• Men achieve a higher peak and overall have higher bone density

• After age 35, men and women lose bone

  • Women lose a lot during menopause since estrogen increased bioavailability & absorption of Ca

What is T score?

• A numerical value of bone density

  • Osteoporosis < -2.5

  • Osteopenia < 1

• Osteoporosis causes a hump in elderly people since the front edge of the vertebrae collapses

• A broken hip is highly common in the elderly, causing a rapid decline

What is osteoporosis?

• Major public health problem in Canada

• 2 million Canadians over 50 have osteoporosis, twice as many women as men

• Estrogen increases calcium absorption

• Osteoporosis is responsible for 80% of fractures in people over 60

• The form of Ca is supplements is important

  • Calcium carbonate should be taken with a meal, Ca citrate can be taken any time

  • Antacids that contain aluminum and Mg may actually increase Ca loss

    • Some are just Ca carbonate, so it is okay

What are the risk factors for osteoporosis?

• Gender

• Age

• Race

• Genetics

• Body Size

• Smoking

• Exercise

• Alcohol abuse

• Diet

What is phosphorus?

• Makes up ~1% of an adult’s body

• 85% is found in the bones and teeth

• More readily absorbed than Ca

• In the extracellular environment, primarily in inorganic forms

  • HPO_^2-, H2PO^4-

• In the intracellular environment, primarily in organic molecules

  • ATP/ADP

  • DNA/RNA

  • Phospholipids

  • Phosphate sugars

• Although not common because it can be efficiently absorbed, deficiency can lead to bone loss, weakness, and loss of appetite

What is magnesium?

• About 50-60% of Mg in the body is found in bone, where it is essential for the maintenance of structure

• Most remaining Mg is present inside cells, where it is the second most abundant intracellular ion after K

• Cofactor for over 300 enzymes → necessary for generating energy from carbs, lipids and proteins

  • Required for Na+/K+ ATPase

• Variable Mg2+ reabsorption in nephron → homeostasis

• Deficiency is rare but can occur with alcoholism, malnutrition, Kidney and GI disease

How is Mg absorbed?

• Paracellular

  • Through a tight junction driven by electrochemical gradients

• Transcellular

  • Carrier-mediated mechanism becomes active to transport magnesium through the intestinal cells

• Mg2+ stabilizes the negative charge on phosphate-containing molecules

What is sulfur?

• Dietary sulphur is found in protein foods and sulphur-containing amino acids in vitamins (B1 & B7)

• Sulphur-containing amino acids (methionine, cysteine) needed for protein synthesis

• Found in nonfood additives

  • Preservative

• Typically considered bad because it is in “unhealthy” foods

• No recommended daily intake for sulphur

• No known deficiencies

How is iron in the body?

• Essential for the delivery of oxygen to cells

• 2 oxygen-containing proteins, hemoglobin and myoglobin, contain iron

• Most of the iron in the body is part of hemoglobin

What is iron?

• Hemoglobin: iron-containing component of the blood

• Iron from animal products is heme iron and from plants is nonheme iron

• Heme iron is more efficiently absorbed than nonheme iron

  • Bioavailability

• Ferritin is the major iron storage protein

  • Intracellular

• Transferrin is an iron transport protein in the blood

• Hemosiderin is an insoluble iron storage compound produced by the body when iron exceeds the storage capacity of ferritin

What is the pathway of heme iron absorption?

1. Heme iron is absorbed as part of the heme group; nonheme is absorbed in the ferrous form (Fe2+)

2. Once inside the mucosal cells, some iron may be bound to ferritin for storage

3. When mucosal cells die, iron that remains bound to ferritin is excreted in the feces

4. Iron that enters the blood is converted to ferric iron (Fe3+) by a copper-containing protein in the cell membrane. The Fe3+ binds to transferrin for transport

5. Transferring transports iron to the liver, bone, and other body cells,

6. When red blood cells die, they are broken down by cells in the liver, spleen, or bone marrow and the iron is released for reuse

7. Excess iron is stored primarily in the liver, bound to ferritin

8. Most iron loss is due to blood loss

What are the DRI for iron?

• Low in 0-6 months because in the third trimester, babies steal iron from mom and store it

• Females have an increased DRI than males due to menstruation

  • If taking the pill need less since it lessens blood loss

• Vegetarians need higher amounts due to the bioavailability of plant sources

What is iron deficiency?

• When there is insufficient hemoglobin, red blood cells are microcytic and hypochromic and unable to deliver sufficient oxygen to the tissues

• ~80% of the world’s population may be iron-deficient, and 30% suffer from iron deficiency anemia

• If hematocrit, hemoglobin, serum iron, or ferritin levels are low, one should be conscious of iron intake

What are the stages of iron deficiceny?

Adequate Iron Status

• Normal iron storage

• Normal iron in plasma

• Normal iron in RBCs

Low Iron Storage

• Low iron storage

• Normal iron in plasma

• Normal iron in RBCs

Depleted Iron Storage

• No iron storage

• Normal iron in plasma

• Normal iron in RBCs

Low Levels of Circulating Iron

• No iron storage

• Low iron in plasma

• Normal iron in RBCs

Iron Deficiency Anemia

• No iron storage

• Very low iron in plasma

• Medium iron in RBCs

What is iron toxicity?

• Hemochromatosis → iron deposits in liver, skin, etc.

• Primary

  • Some genetic mutation influencing the likelihood

• Secondary

  • Too much iron in the diet or other dietary factors

What is zinc?

• Most abundant intracellular trace element

• Essential in the diet for growth and development

• Better absorbed from animal sources than plant sources

  • Vegans ~50% more vulnerable due to the lower bioavailability of zinc from vegan sources

• Can be bound by phytates, affecting bioavailability

• Involved in the functioning of over 300 different enzymes, including superoxide dismutase, important for protecting cells from free radical damage

• Zinc homeostasis within cells is maintained by the ZIP (zinc transporter) and ZnT (zinc transporter protein)

What is the regulation of zinc absorption?

• When zinc is low, more zinc moves from the lumen into the mucosal cells and from vesicles into the cytosol, and little metallothionein is synthesized

• When zinc intake is high, little zinc is transported from the lumen into the mucosal cells, and more zinc moves out of the mucosal cells into the lumen and from the cytosol into vesicles

• The synthesis of metallothionein, which binds zinc and limits its uptake into the blood, increases

What are zinc fingers?

• Small, functional protein domains that use zinc ions to stabilize their structure, enabling them to bind DNA, RNA, or proteins

• Binds into the spiral of DNA like fingers

What are zinc lozenges?

• Started with an agar plate, and when zinc was added, growth stopped

• Created the conclusion that zinc helps with colds

• Studies using zinc with COVID infection was there was no significant difference between zinc and common care

How is copper absorbed?

• High levels of dietary zinc can inhibit copper absorption by stimulating the synthesis of metallothionein, which then preferentially binds copper and limits its absorption

• Zinc and copper are in competition for binding to metallothionein for storage

  • Since Zinc is more common, there is an association with copper deficiency

What are thyroid hormones?

• Tyrosine

• Thyroxine (T4)

  • Most common

  • Not biological active form

  • Can convert into T3

• Triiodothyronine (T3)

  • Biologically active form

*Every cell has receptor for thyroid hormones

What is the pathway for thyroid hormones?

1. T4 & T3 circulate in the blood bound to plasma proteins

2. T4 and T3 enter the cell, where a selenium-containing enzyme converts T4 to T3

3. T3 enters the nucleus and binds to a nuclear protein receptor

4. The T3-protein receptor complex then binds to a regulatory region of a target gene

5. Transcription of the gene is turned on, increasing the amount of mRNA made

6. mRNA directs translation, increasing the synthesis of the protein coded by this gene

7. There is an increase in the amount of protein, and hence the cellular functions and body processes affected by this protein

What is chromium?

• Least understood trace mineral

• Beneficial for blood glucose regulation

• When chromium is present, a small peptide inside cells becomes active and enhances the action of insulin by binding to the insulin receptor, which increases glucose uptake

• When chromium is deficient, the active peptide is not formed and thus cannot bind the insulin receptor

  • The result is that insulin is less effective and less glucose can enter the cell

What is fluoride?

• Naturally occurring mineral

  • Rocks with fluoride will leech into water

• Helps strengthen enamel

What is fluoride toxicity?

• High doses can cause staining and pitting of the teeth

• Exhibits why fluoride is good

  • Fluoride attaches itself to the teeth