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Mineral metabolism, dental bioch212 1

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Biochemistry …

Biochemistry
Second Year

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  • 1. 1
  • 2. 2 CLASSIFICATION OF MINERALS Two Types 1. PRINCIPAL ELEMENTS (MACROMINERALS) 2. TRACE ELEMENTS (MICROMINERALS) 1. PRINCIPAL ELEMENTS -Constitute about 60-80% of body’s inorganic materials. -It required in amounts greater than 100 mg/day. • CALCIUM • MAGNESIUM • SODIUM • POTASSIUM • PHOSPHORUS • CHLORIDE • SULPHUR 2. TRACE ELEMENTS -Required in amount in amount less than 100 mg/day. -Subdivided into three categories a. Essential Trace elements b. Possibly Essential Trace Elements c. Non Essential trace Elements
  • 3. 3 CALCIUM - Most abundant among all minerals in body - Total content about 1-1.5 kg in adult person - As much as 99% of it present in bones and teeth. - 1% of calcium found outside the skeletal tissue performs a wide variety of functions. =BIOCHEMICAL FUNCTION= 1. Development of bones and teeth -Osteoblast are responsible for Bone formation. - Osteoclast are responsible for Bone demineralization. 2. Muscle contraction -Ca ions interact with troponin C to trigger muscle contraction. 3.Blood coagulation Several reactions in the cascade of blood clotting process depends on Ca ions ( Factor IV)
  • 4. 4 4.Nerve impulse transmission - Ca ions is necessary for the transmission of nerve impulse. 5.Membrane integrity & permeability -Ca ions influence the membrane structure. 6.Activation of enzymes -Ca ions are needed for direct activation of enzymes such as- -PANCRETIC LIPASE -ATPase 8.Release of Hormone -The release of certain hormone from endocrine glands is facilitated by Ca. e.g. Insulin PTH Calcitonin 9.Secretory process -Ca ions regulates microfilament & microtubule mediated process such as *Endocytosis * Exocytosis
  • 5. 5 =DIATARY REQUIREMENT= ADULT MAN- 800 mg/day ADULT WOMAN- During Pregnancy & Lactation- 1500mg/day Postmenopausal- 1500mg/day =ABSORPTION OF CALCIUM IN GI TRACT= -Mostly absorbed in Duodenum by energy dependent process. Factor Promoting Ca Absorption 1. Vit D-(Through its active form calcitriol) Vitamin D (active form) Increased synthesis of Ca Binding protein in intestinal epithelial cells. Increased Ca Absorption
  • 6. 6 2. PTH PTH increased Ca Absorption through increased synthesis of calcitriol (active form of vitamin D). 3. Low pH in intestinal lumen is favoring Ca absorption. 4. Lactose Lactose increased Ca uptake by intestinal cell 5. Lysine & Arginine increased Ca absorption. Factors inhibiting Ca Absorption 1.Phytate & Oxalate -Forms insoluble salt of calcium and interfere with Ca absorption. 2.Dietary Phosphate - High content of dietary phosphate result in formation of insoluble calcium phosphate and prevent Ca uptake 3.Free fatty acid -The free fatty acids react with calcium to form insoluble Ca soap.
  • 7. 7 4.High pH in intestinal lumen -Alkaline condition in intestinal lumen is unfavorable for Ca absorption. 5.High content of dietary fiber - High content of fiber in diet interfere with Ca absorption. =CIRCULATING FRACTIONS OF CALCIUM
  • 8. 8 =Plasma Calcium Level= Normal level of Total Ca = 9-11 mg/dl Normal level of ionized Ca = 5mg/dl (ACTIVE Ca) Normal level of bound Ca = 4-5mg/dl = HORMONAL REGULATION OF PLASMA Ca LEVEL= -Major Hormonal factors maintaining homeostasis of Ca are 1. Calcitriol or 1,25 DHCC 2. PTH 3. Calcitonin 1.Calcitriol or 1,25 DHCC - The physiologically active form of vitamin D called calcitriol or 1,25 DHCC Calcitriol increased synthesis of specific Ca binding protein in intestinal wall Increased intestinal absorption of Ca & Phosphate Increased Blood Ca level
  • 9. 9 Calcitriol increased calcium uptake by Osteoblast of bone Promotes Calcification, mineralization and remodeling of bone 2. PTH (Parathyroid hormone) -PTH hormone secreted by two pairs of Parathyroid glands. -PTH (mol wt 95000) is a single chain polypeptide containing 84 amino acid. Pre-Pro PTH Pro-PTH Active PTH Secreted in blood -Low level of Ca ion concentration promoted release of PTH from parathyroid gland (Negative Feedback). -Prime function of PTH- Increased serum Ca level Three site of action of PTH- - A. Bone - B. Kidney - C. Intestine
  • 10. 10 A. Action on Bone by PTH - PTH causes decalcification or demineralization of bone. - This process is carried out by Osteoclast. B. Action on Kidney by PTH - PTH increased Ca reabsorption by Renal tubules Increased Blood Calcium level -This is the most rapid action of PTH to increased blood Ca level Leads to Increased blood Ca level
  • 11. 11 C. Action on Intestine by PTH PTH increased synthesis of Calcitriol Increased intestinal absorption of Ca Increased blood Ca level 3. Calcitonin -Calcitonin is secreted by parafollicular cell of thyroid gland. -Opposite action of PTH. -Calcitonin thus promote calcification by increasing the activity of Osteoblast. -Calcitonin decreased bone resorption & increased excretion of Ca through urine Decreased blood Calcium level
  • 12. 12 HOMEOSTASIS OF CALCIUM by PTH and CALCITONIN
  • 13. 13 = Diseased state= HYPERCALCEMIA 1.Serum Ca level increased. 2. Hypercalcemia is associated with hyperparathyroidism which is caused by increased activity of parathyroid gland. 3.Increased Alkaline Phosphatase activity. 4.Increased urinary excretion of Ca & P. 5.Formation of urinary calculi. -Clinical symptom of Hypercalcemia- *Lethargy *Muscle Weakness *Loss of appetite *Constipation *Nausea *Increased myocardial contractility
  • 14. 14 HYPOCALCEMIA -Fall of serum Ca below 7 mg/dl causing TETANY. -The clinical sign & symptoms of Tetany includes - Neuromuscular irritability - Spasms - Convulsion -Hypocalcemia is mostly due to Hypoparathyroidism which may happen after accidental surgical removal of parathyroid gland or due to an autoimmune disease. - Hypocalcemia is very serious and life threatening condition.
  • 15. 15 RICKETS -Defective calcification of bone. -Causes due to *Low level of Vit D in body due to dietary deficiency of Ca and P. -Serum Ca or P may be low or normal -Increased activity of Alkaline Phosphatase is characteristic feature of Rickets. OSTEOPORESIS -Demineralization of bone resulting in the progressive loss of bone mass. -Elderly people over age of sixty in both sexes are at risk but most predominantly occur in postmenopausal women. -It results frequent bone fracture in elderly. -Occurs due to less ability of formation of Calcitriol from Vit D in elderly. OR Deficiency of sex hormone in postmenopausal women.
  • 16. 16 Treatment -Estrogen administration along with calcium supplementation in combination with Vitamin D to postmenopausal women reduce the risk of Fracture. -Higher dietary intake of Ca (about 1.5 g/day) is recommended for elderly people. =FACTORS INCREASING THE RISK OF OSTEOPOROSIS=
  • 17. 17 SODIUM -Chief cation of extra cellular fluid -About 50% of body sodium presence in Bone, 40% in extra cellular fluid & 10% in soft tissue. =DIETARY REQUIRMENT= Normal individual- 5-10 gm/day as NaCl(10gm NaCl= 4gm Na) Hypertensive- Not more than 1gm/day = BIOCHEMICAL FUNCTION= 1. Regulate Acid-Base balance in association with Cl- and Bicarbonate. 2. Maintain Osmotic pressure & fluid balance. 3. Necessary for normal muscle irritability and cell permeability. 4. Promotes intestinal absorption of Glucose, Galactose & Amino Acid.
  • 18. 18 =PLASMA SODIUM LEVEL= -Normal serum level (Present as extra cellular cations) = 135-145meq/L -Blood cellular level= 35meq/L =ABSORPTION= -Absorbed mainly on GI Tract -Less than 2% normally found in feces =EXCREATION= -Kidney is the major source of excretion -800mg/day filtered through glomeruli -99% of this reabsorbed by renal tubules by active process controlled by ALDOSTERONE. -Through skin in case of extreme sweating. However there is individual variation in sodium loss through sweat.
  • 19. 19 =DISEASED STATE= HYPERNATREMIA -This condition is characterized by an elevation in the serum sodium level. -The symptom include increased blood volume and blood pressure. -Hyperactivity of Adrenal cortex (CUSHING’S SYNDROME) -Prolonged use of Cortisone, ACTH, Sex Hormones -Loss of water from the body (In Dehydration). HYPONATREMIA - Serum sodium levels falls below the normal level -Hypernatremia Occurs due to -Occur due to -Diarrhea -Prolonged vomiting -Chronic Renal Disease -Adrenocortical insufficiency (Addison's DESEASE) -Edema occurred due to water retention along with hypernatremia.
  • 20. 20 IRON -Total contain about 3-5 gm in an adult individual. -70% presence in erythrocytes of blood as a constitute of hemoglobin ,5% in myoglobin in muscles. -Heme is the most predominant iron containing substance. -Constituents of several proteins & enzymes like Hemoglobin Myoglobin Cytochrome Xanthine Oxidase -Certain other proteins contain ‘non- heme’ iron like Transferrin Ferritin Hemosiderin
  • 21. 21 =ABSORPTION, TRANSPORT & STORAGE= -In normal individual 10% of dietary iron is usually absorbed. -Dietary iron mainly absorbed in stomach and duodenum. -Iron mainly found in foods in ferric form (Fe+++) which bound to protein and organic acids. -Iron in ferrous form is soluble and readily absorbed.
  • 22. 22 =ABSORPTION, TRANSPORT & STORAGE= LUMEN OF GIT MUCOSAL CELL OF GIT PLASMA TISSUES Food Fe Fe+++( Ferric form) Fe++ apoferritine Fe++ Fe+++ FERRITIN Fe++ Fe++ Fe+++ Ferroxi dase Cerulloplasmin or Ferroxidase II Apotransferrin Transferrin Ferro reductase LIVER Ferritin Hemosidererin BONE MARROW (Hb) MUSCLE (Mb) OTHER TISSUE (Cyts) -HCl -Organic acid -Ascorbic acid -Cysteine
  • 23. 23 =STORAGE OF IRON As Ferritin= Liver Spleen Bone Marrow Hold 25% of Fe by weight As Hemosiderin -Hold 35% Fe by weight. -Hemosiderin accumulates in the body particularly in Liver and spleen when supply of iron is excess than body demand.
  • 24. 24 =BIOCHEMICAL FUNCTION= -Hemoglobin & Myoglobin required Fe for transport of O2 & CO2 -Cytochrome required iron for electron transport chain & oxidative Phosphorylation -Fe associated for effective immunocompetence of our body =DISEASED STATE= IRON DEFICIENCY ANEMIA -This is the most prevalent nutritional disorder worldwide. -Mostly occurred in growing children, adolescent girls, pregnant & lactating women -Characterized by Microcytic Hypochromic anemia with reduced blood Hb level (<12 g /dl.) -Features -Apathy -Sluggish metabolic activity -Retarded growth -Loss of Appetite etc
  • 25. 25 HEMOSIDEROSIS -Due to excessive Fe in the body -In repeated blood transfusion -Patient of Hemolytic anemia -Patient of Hemophilia -Excessive Fe deposited as Ferritin & Hemosiderin. -Due to high intake of Fe. HEMOCHROMATOSIS -Iron is deposited in tissue like Liver, Spleen, Pancreases, Skin. -Features are Bronzed pigmentation of skin Cirrhosis Pancreatic Fibrosis -Hemochromatosis causes a condition known as Bronze Diabetes.
  • 26. 26 PHOSPHORUS -Adult male person contained about 1kg of phosphorus and found in every cell of the body. -Mostly combined with Ca to deposit in bone & teeth(80%). -About 10% of body P is found in muscle & blood in association with protein, carbohydrate & lipid. -Remaining 10% is widely distributed in various chemical compounds. =SERUM PHOSPHORUS LEVEL= -In whole Blood- 40mg/dl -Serum level- 3-4mg/dl - Serum Phosphate -Free Form 40% -Complex form with Ca, Mg, Na, K ions is about 50%
  • 27. 27 =ABSORPTION= -Absorption mostly from Jejunum. -Calcitriol increased absorption of P among with Ca. -Acidity in intestinal lumen increased absorption of P. =EXCRETION= -Urinary excretion about 500mg/day. -Renal Threshold 2mg/dl. -Reabsorption of phosphate by renal tubules is inhibited by PTH.
  • 28. 28 =BIOCHEMICAL FUNCTION= -Phosphorus is essential for development of Bone and teeth. -It play a central role for formation & Utilization of high energy phosphate compound like ATP. -Required for formation of Phospholipids, phosphoprotein, Nucleic acid. -As phosphate buffer for maintenance of pH of blood (around 7.4) & cell.
  • 29. 29 MAGNESIUM -Body contain about 20 gm of Mg. -70% presence in bone in combination of Ca & P. -30% in soft tissues & body fluids. =DIATERY REQUIREMENT= -Adult Male= 350mg/day -Adult Female= 300mg/day = SERUM LEVEL= NORMAL LEVEL= 2-3mg /dl -Ionized form-60% -Protein Bound-30% -Combination with other ions-10%
  • 30. 30 =BIOCHEMICAL FUNCTION= -Required for formation of Bone & Teeth. -Mg ion serve as cofactor for several enzymes requiring ATP like *Hexokinase *Glucokinase -For proper neuromuscular function, Low Mg level leads to neuromuscular irritability. =DISEASES STATES= Mg Deficiency causes -Neuromuscular Irritation -Weakness -Convulsion Low level of Mg observed in -Uremia -Rickets -Abnormal Pregnancy
  • 31. 31 POTASSIUM - Potassium is a principle intracellular cation. =ABSORPTION= -90% Absorption in GI Tract. -Very little loss through feces, however a subject with diarrhea a good proportion of potassium lost in feces. =BIOCHEMICAL FUNCTION= -Potassium maintain intracellular osmotic pressure. -It is required for the regulation of acid base balance & water balance in the cell. -Potassium is required for transmission of nerve impulse. -Extra cellular K ions influence cardiac muscle activities.
  • 32. 32 =POTASSIUM BALANCE= =NORMAL VALUE IN SERUM- 3.5-5 mmol/L
  • 33. 33 =DISEASE STATES= Serum Potassium concentration is maintained within a narrow range. HYPERKALEMIA -Increased serum potassium level is called Hyperkalemia. -Observed in -Renal Failure -Addison’s Disease (Adrenocortical insufficiency) -Diabetic Coma -Severe Dehydration
  • 34. 34 =HYPOKALEMIA -Decreased serum potassium level is called Hypokalemia. -Observed in -Over activity of adrenal cortex (Cushing Syndrome) -Prolonged cortisone therapy -Intravenous administration of potassium free fluid. -Prolonged Diarrhea & vomiting -Prolonged administration of Insulin
  • 35. 35 COPPER -Body contain about 100mg copper =DIETARY REQUIREMENT= Adult= 2-3 mg/day Infants & Children= 0.5-2 mg/day = PLASMA LEVEL= Normal level in plasma= 100-200 mg/dl -95% bound to Cerulloplasmin -5% loosely held to Albumin
  • 36. 36 =BIOCHEMICAL FUNCTION= -Essential component of several enzymes like -Cytochrome Oxidase -Catalase -For synthesis of Hb ( Cu is a important component of ALA Synthase needed for heme synthesis) -Cerulloplasmin act as Ferroxidase, involved conversion of iron from ferrous to ferric form. -For synthesis of Melanin & Phospholipids -For development of Bone & Nervous System
  • 37. 37 2.MENKE’S DISEASE -Due to defect of intestinal absorption of Cu. -Symptoms of Menke’s Disease are -Decreased copper in plasma & urine -Anemia -Depigmentation of hair. =DISEASE STATES= 1. COPPER DEFICIENCY Severe deficiency of copper causes -Demineralization of Bone and -Demyelination of nervous tissue -Anemia -Fragility of arteries -Hypo pigmentation of skin -Graying of hair
  • 38. 38 3. WILSON’S DISEASE OR HEPATOLENTICULAR DEGENERATION =This disorder of abnormal copper metabolism is characteristics by the following manifestations -Copper deposited in liver & lenticular nucleus of brain leads to Hepatic cirrhosis & brain necrosis. -Low level of copper & ceruloplasmin in plasma -Increased excretion of copper in urine. -Copper deposition in kidney causes renal damage -Intestinal absorption of copper is very high , about 4-6 times higher than normal. =Probable cause of Wilson's disease. 1. A failure to synthesis of ceruloplasmin or an impairment in the binding capacity of copper to ceruloplasmin or both Copper is free in plasma which easily enter into tissue (liver, brain, kidney) Binds with protein & get deposited. 2.Reduced intestinal excretion of copper may be also responsible As a result
  • 39. 39 IODINE =Total body contains 20mg of iodine =80%presence in Thyroid gland =Muscle, Salivary gland & Ovaries also contain some amount of iodine =ABSORPTION, STORAGE,EXCRETION= -Absorb as Iodide in small intestine. -Normally 30% of Dietary iodine is taken by intestinal cell. -80% body iodide stored as Iodothyroglobulin in thyroid gland. This protein contains Thyroxin, Diiodotyrosine & Triiodothyronine in different proportion. -Excretion mainly through Kidney.
  • 40. 40 =BIOCHEMICAL FUNCTION= -Required for synthesis of Thyroid hormone namely Thyroxin(T4) and Triiodothyronine(T3). =DISEASES STATES= The disorder of iodine metabolism are *Simple goiter *Toxic goiter =PLASMA IODINE= -Normal concentration of plasma iodine is 4-10 mg/dl. -Most of it present as Protein Bound Iodine (PBI) and represent the iodine contained in circulating thyroid hormones. -RBC donot contain any iodine.
  • 41. 41 ZINC -The total content of Zinc in an adult body is about 2 gm. -Prostate Gland is very rich in Zn ( 100 mg/dl). -Zn is mainly an intracellular element SERUM Zn -Normal serum concentration of Zn is about 100mg/dl. DISEASE STATES -Zinc deficiency is associated with *Growth Retardation *Poor wound healing *loss of taste sensation *Impaired spermatogenesis *Anemia *Loss of appetite
  • 42. 42 -Congenital malformation of fetus if deficiency in intrauterine life. -Psychiatric disorder like *Depression *Other psychiatric disorders ZINC TOXICITY -The manifestation of Zn toxicity are *Nausea *Gastric Ulcer *Pancreatitis *Anemia *excessive salivation
  • 43. 43 FLUORINE -Fluuorine is mainly found in bone & teeth DIETARY REQUIREMENTS AND SOURCES -Daily requirment is less than 2ppm -drinking water is the main sources BIOCHEMICAL FUNCTION -Fluoride prevents the development of Dental carries ( It forms a protective layer of acid resistant fluoroapatite with Hydroxyapatite of the enamel and prevents the tooth decay by bacterial Acid) -Fluoride is necessary for the proper development of bone. -Fluoride inhibits the activities of certain enzymes *Fluoroacetate inhibits Acotinase ( of TCA cycle) *Sodium Fluoride inhibits Enolase ( of Glycolysis) =DISEASE STATES= •Dental Caries •Dental fluorosis