Dental Biochemistry 2 – (Lec. 8)

Minerals

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• A few minerals are required for the normal growth and maintenance of the body. If the daily requirement is more than 100 mg, they are called major elements.

• If the requirement of certain minerals is less than 100 mg/day, they are known as minor elements or micro-minerals or trace elements.

• Major elements Trace elements

1. Calcium 1. Iron

2. Magnesium 2. Iodine

3. Phosphorus 3. Copper

4. Sodium 4. Manganese

5. Potassium 5. Zinc

6. Chloride 6. Molybdenum

7. Sulfur. 7. Selenium

8. Fluoride

• The following minerals are toxic and should be avoided: aluminium, lead, cadmium and mercury

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CALCIUM (Ca++) • Total caIcium in the human body is about 1 to 1.5

kg, 99% of which is seen in bone and 1% is extracellular.

• Sources of Calcium

• Milk is a good source for calcium. Egg, fish and vegetables are medium source for calcium. Cereals (wheat, rice) contain only small amount of calcium.

• Daily Requirement of Calcium

• An adult needs 500 mg per day and a child about

• 1200 mg/day. Requirement may be increased to 1500 mg/day during pregnancy and lactation.

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Absorption of Calcium • Absorption is taking place from the first and

second part of duodenum. Absorption requires a carrier protein, helped by calcium-dependent ATPase.

• Factors affecting absorption of calcium are:

i. Vitamin D: Calcitriol induces the synthesis of the carrier protein (Calbindin) in the intestinal epithelial cells, and so facilitates the absorption

of calcium.

ii. Parathyroid hormone: It increases calcium transport from the intestinal cells.

iii. Acidity: It favors calcium absorption.

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iv. Phytic acid: It is present in cereals. It reduces uptake of calcium. Cooking reduces phytate content.

v. Oxalates: They are present in leafy vegetables, which cause formation of insoluble calcium oxalates; so absorption is reduced.

vi. Phosphate: High phosphate content will cause precipitation as calcium phosphate.

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Functions of Calcium 1. Activation of enzymes:

• various regulatory kinases.

• pancreatic lipase.

• enzymes of coagulation pathway.

• Rennin (milk clotting enzyme in stomach).

2. Muscles:

• Calcium mediates excitation and contraction of muscle fibers.

• Calcium decreases neuromuscular irritability.

• Calcium deficiency causes tetany.

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3. Calcium is necessary for transmission of nerve impulses through synaptic region.

4. Secretion of hormones: Calcium mediates secretion of insulin, parathyroid hormone, etc. from the cells.

5. Second messenger: Calcium and cyclic AMP are second messengers of different hormones. One example is glucagon.

6. Coagulation: Calcium is known as factor IV in blood coagulation cascade.

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7. Myocardium: Ca+ + prolongs systole. In hypercalcemia, cardiac arrest is seen in systole. This fact should be kept in mind when calcium is administered intravenously. It should be given very slowly.

8. Bone and teeth: The bulk quantity of calcium is used for bone and teeth formation. Bones also act as reservoir for calcium in the body.

(N.B. Osteoblasts induce bone deposition and osteoclasts produce demineralization).

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Factors Regulating Blood Calcium Level

(A) Vitamin D • The active form of vitamin D is called calcitriol.

• The calcitriol induces a carrier protein in the intestinal mucosa, which increases the absorption of calcium. Hence blood calcium level tends to be elevated.

(B) Parathyroid Hormone (PTH)

• i. This hormone is secreted by the four parathyroid glands.

• ii. Control of release of the hormone is by negative feedback by the ionized calcium in serum.

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Mechanism of action of PTH i. PTH acts through cyclic AMP. Increase Ca absorption from intestine.

ii. PTH and bones:

• In the bone, PTH causes demineralization or decalcification.

• It induces pyrophosphatase in the osteoclasts. The number of osteoclasts are also increased.

• Osteoclasts release lactate into surrounding medium which solubilizes calcium.

• PTH also causes secretion of collagenase from osteoclasts. This causes loss of matrix and bone resorption.

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iii. PTH and kidney:

• In kidney, PTH causes decreased renal excretion

of calcium and increased excretion of phosphates.

• The action is mainly through increase in

reabsorption of calcium from kidney tubules.

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(C) Calcitonin • i. It is secreted by the thyroid parafollicular or clear cells.

Calcitonin is a single chain polypeptide. It contains about 32 amino acids.

• ii. Calcitonin secretion is stimulated by serum calcium.

• iii. Calcitonin level is increased in medullary carcinoma of thyroid and therefore is a tumor marker.

• iv. Calcitonin decreases serum calcium level. It inhibits resorption of bone. It decreases the activity of osteoclasts and increases that of osteoblasts.

• v. Calcitonin and PTH are directly antagonistic. The PTH and calcitonin together promote the bone growth and remodeling.

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Calcitonin, Calcitriol and PTH Act Together

• When blood calcium tends to lower, PTH secretion is stimulated and calcitonin is inhibited; bone demineralization leads to entry of more calcium into blood.

• When blood calcium is increased, PTH is inhibited and calcitonin is secreted, causing more entry of calcium into bone.

• Bone acts as the major reservoir of calcium

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(D) Phosphorus There is a reciprocal relationship of calcium with phosphorus. The ionic product of calcium and phosphorus in serum is kept as a constant. (In normal adults, calcium = 10 mg/dl x phosphorus 4 mg/dl; so ionic product is 40).

(E) Children

In children, the calcium level tends to be near the upper limit. In children, ionic product of calcium and phosphorus in blood is about 50 (instead of 40 in normal adults).

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Homeostasis of serum calcium

Gut ↓ ← D ← PTH PTH Bone ↔ Serum calcium ← Reabsorption of D. C. Calcium from kidney tubules C= Calcitonin; D= Vitamin D; PTH= Parathyroid hormone

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IRON (Fe) Distribution of Iron

• Total body iron content is 3 to 5 gm, 75% of which is in blood. Iron is present in almost all cells.

• Heme containing proteins are hemoglobin, myoglobin, cytochromes, cytochrome oxidase, catalase.

• Non-heme iron containing proteins are transferrin, ferritin, hemosiderin.

• Blood contains 14.5 g of Hb per 100 ml. About 75% of total iron is in hemoglobin, and 5% is in myoglobin and 15% in ferritin.

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Factors Influencing Absorption of Iron • i. Reduced form of iron: Only Fe++ (ferrous) form

(reduced form) is absorbed. Fe+++ (ferric) form is not absorbed.

• ii. Ascorbic acid: Ferric ions are reduced with the help of gastric HCl, and ascorbic acid. Therefore these will favor iron absorption.

• iii. Interfering substances: Iron absorption is decreased by phytic acid (in cereals) and oxalic acid (in leafy vegetables) by forming insoluble iron salts. Calcium, copper, lead and phosphates will inhibit iron absorption.

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Mucosal Block Theory • i. Duodenum and jejunum are the sites of

absorption. Iron metabolism is unique because homeostasis is maintained by regulation at the level of absorption and not by excretion. No other nutrient is regulated in this manner.

• ii. When iron stores in the body are depleted, absorption is enhanced. When adequate quantity of iron is stored, absorption is decreased. This is referred to as "mucosal block" of regulation of absorption of iron.

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• iii. Iron in the intestinal lumen enters the mucosal cell in the ferrous state. This is bound to transferrin molecule present on the brush border surface of intestinal cell.

• iv. This is then complexed with a specific receptor. The iron-transferrin-receptor is internalized. Iron is taken in by the cells, and receptor molecules are externalized.

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• v. This receptor mediated uptake is more in iron deficient state. When iron is in excess, receptors are not produced; this is the basis of "mucosal block".

• vi. The absorbed iron binds with apoferritin, to form ferritin. It is kept temporarily in the mucosal cell. If there is anemia, the iron is further absorbed into the blood stream.

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Iron Transport in Blood • i. Transport form of iron is transferrin. It is a beta1

globulin. Normal plasma level of transferrin is 250 mg/100 ml. In iron deficiency, this level is increased.

• ii. In iron deficiency anemia, Total iron binding capacity (TIBC) is increased (transferrin level is increased); but serum iron level is reduced.

• iii. Transferrin takes up iron with the help of ferroxidase.

• In blood, ceruloplasmin is the ferroxidase, which oxidizes ferrous to ferric state.

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Ferroxidase

• Apo-transferrin ----------------------------------------------------------------------------------------1) Transferrin combined

• +2 Fe+++ 1/2 02 with 2 Fe+++ + H2O

• Storage of Iron • The storage form is ferritin. It is seen in

intestinal mucosal cells, liver, spleen and bone marrow.

• In iron deficiency anemia, ferritin content is reduced.

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Iron Is Conserved

• i. When RBC is lysed, hemoglobin enters into circulation. Being a small molecular weight substance, Hb will be lost through urine. To prevent this loss, Hb is immediately taken up by haptoglobin (Hp).

• ii. When the globin part is removed from Hb, the heme is produced, and is released into circulation. In order to prevent its excretion through urine, heme is bound with hemopexin.

• iii. Iron is very precious for biological systems. Hence these elaborate mechanisms are necessary for conservation inside the body.

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Excretion of Iron • i. Iron is a one-way element. That is, very little of it is

excreted.

• The regulation of homeostasis is done at the absorption level.

• Almost no iron is excreted through urine. Feces contains unabsorbed iron as well as iron trapped in the intestinal cells.

• ii. Any type of bleeding will cause loss of iron from the body. Menstrual flow is the major cause for loss of iron in women.

• iii. All the cells in skin contain iron. The upper layers of skin cells are constantly being lost, and this is another route for iron loss from the body.

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