Minerals and Water « Metabolism + Calcium, Phosphorus © Magnesium * Sodium * Potassium and Chloride * tron © Copper * Ziarc * Iodine * Selenium © Manganese * Cobalt © Chromium © Molybeduum © Fluoride. According to the body needs, minerals may be divided into two groups: 1, Macrominerals: (Major Elements) They are required in amounts greater than 100 mg/day. They include six elements : calcium, phosphorus, magnesium, sodium, potassium and chloride. Il. Microminerals (Trace Elements): They are required in amounts less than 100 mg/day. They include ten elements: chromium, cobalt, copper, fluoride, iodine, iron, manganese, molybdenum, selenium and zinc.) 1. MACROMINERALS TE A. Sources: 1. Milk and milk products (the richest sources). 2. Beans, leafy vegetables and egg yolk. B. Absorption: 1. Calcium is absorbed by an active transport mechanism in the upper small intestine. 2. Absorption requires calcium binding protein present in the intestinal mucosal cells. 3. Absorption is regulated by: (a) Vitamin D: (1, 25-dihydroxycholecalciferol (= calcitriol): Through the formation of calcium binding, protein. (b) Parathyroid hormone: Through the conversion of vitamin D to 1, 25- dihydroxycholecalciferol in the kidney. [636]Minerals and Water Metabolism ox) 4, Factors affecting calcium absorption: (a) Factors promoting calcium absorption: (1) High protein diet : Amino acids combine with calcium to form soluble calcium salts which are easily absorbed. (2)pH: An acidic pH in the upper small intestine is essential for calcium absorption. (3) High dietary lactate or citrate that form soluble salts with calcium. () Factors inhibiting calcium absorption: (1) High dietary phosphate, oxalate and phytate which form insoluble salts with calcium. (2) Alkalinity: Excessive alkali intake as during treatment of peptic ulcer decreases calcium absorption. (3) Impaired fat absorption: Fatty acids form insoluble calcium soaps with calcium. . Body calcium: 1. Calcium is the most abundant mineral in the body (1200 g). 2. Most of calcium is present in the skeleton (bones and teeth) 99%, in the form ‘of hydroxyapatite: 3 Ca,(PO4),. Ca(OH), i. three molecules of calcium phosphate and one molecule of calcium hydroxide. 3. Calcium salis in bones are not inert. They are in a constant state of turnover in skeleton being deposited in sites of bone formation and released at sites of bone resorption. In adult male about 700 mg calcium enter and leave bones each day. 4. Calcium in bones acts as a reservoir which helps to stabilize calcium ions in plasma and ECE. 5. The remaining 1% of calcium are present in body fluids and other tissues. D. Blood calcium: 1. Blood calcium level ranges from 9-11 mgjdl, 2. Blood calcium lies entirely in the plasma (RBCs contain no calcium). 3. Plasma calcium is present in three forms: (a) Ionized (diffusable): 50% (5 mgs%) + Its deficiency causes tetany. (t) Non-ionized (diffusable): 5% (1 mgs%) « Complexed with organic ions eg, citrate, () Non-ionized (non diffusable): 45% (4.5 mgs%) « It is bound to protein mainly albumin. + — Its deficiency occurs with conditions of hypoproteinaemia and causes no tetany, 4, Factors affecting blood calcium: (a) Hormonal regulation: Four hormones are concerned with regulation of blood calcium. These are parathyroid hormone, active vitamin D (calcitriol), calcitonin and Katacalcin, f(es Text Book of Biochemistry (1) Parathyroid hormone: It increases blood calcium level through: + Mobilization of caleium from bones (bone resorption). + Absorption of calcium ftom intestine (through conversion of vitamin D into calcitriol “active vitamin D" in the kidney). + Reabsorption of calcium by renal tubules. 2. Caleitriol: 1, 25 dihydroxycholecalciferol: It increases blood calcium level through: * Absorption of calcium from the intestine. + Reabsorption of calcium by renal tubules. * Mobilization of calcium from bones. 3, Calcitonin and Katacalein: + These two hormones are secreted by the parafollicular or “C” cells of the thyroid gland * Their function is doubtful, but they may be released in response to hypercalcemia and decrease blood calcium level through inhibition of its mobilization from bones, or increased calcium deposition in bones. FACTORS AFFECTING PLASMA CALCIUMMinerals and Water Metabolism (b) Other factors: (1) Solubility product: Normally Ca/P ratio must be constant. CaxP in children is 50 and in adults is 40. If plasma phosphate increases (as in renal feuilure) the plasma calcium decreases to keep the ratio constant. (2) Blood pH: Ionization of calcium occurs at normal blood pH (7.4), Alkalosis decreases ionized calcium. (3) Plasma proteins: In cases of hypoproteinaemia, the non-diffusable calcium decreases. E. Functions of calcium: 1, Unionized calcium: It is found in the structure of bones and teeth, act as calcium reservoir. 2. Tonized calcium: It is important for: (a) Transmission of nerve impulses. (b) Contraction of muscles with the presence of ATPase and troponin-e-. (©) Decrease of neuromuscular excitability. Deficiency of ionized calcium leads to tetany. (@) Blood coagulation mechanisms and milk rennin clotting. (e) Maintenance of cell membrane permeability for water and other ions. (f) Activation of enzymes eg. pyruvate kinase, pancreatic lipase. (g) Mediation of some hormone responses e.g. it acts-together with. calmodulin- as third messenger for hormones depending on cyclic AMP, (Chapter 17) (i Sarcoplasmic reticulum of skeletal muscle contains calsequestrin-calcium binding protein which helps in opening, of calcium channels for contraction. F, Excretion: 1. Most of calcium excretion is eleminated with faeces, 2. Small amount of calcium is excreted in urine (about 200 mg/day). G. Requirements: 1, Adult men and women: 800 mg/day. 2. Children, pregnant and lactating women: 800-1200 mg/day. H. Alterations of plasma calcium: 1. Hypercalcemia: It is caused by: (a) Primary hyperparathyroidism: Usually due to adenoma (benign tumor). Serum calcium usually ranges 12-20 mg/dl. (b) Tertiary hyperparathyroidism. (©) Excess intake of vitamin D or calcium or both, Usually it is due to overdosage or self-medication with vitamin D.ee) Text Book of Biochemistry patients who received, for long periods, excessive absorbable alkalies and milk (source of calcium), for the treatment of peptic ulcer. (e) Bone diseases: As malignancy, leukaemia, multiple myeloma and Paget disease. (f) Drugs: As thiazide diuretics. (g) Other causes: As thyrotoxicosis, cushing’s syndrome and sarcoidosis, . Hypocalcemia: It is caused by = (a) Hypoparathyroidism. (B) Alkalosis. (c) Kidney diseases where activation of vitamin D is inhibited. N.B. In all these conditions, if ionized calcium is much decreased, tetany with carpopedal spasm results. teed dal A. Sources: hi Bs 3. Milk and milk products Fish, meat, liver and kidney. Leafy vegetables and egg: yolk. B. Absorption: : Phosphorus {in the form of phosphate) is absorbed by an active transport mechanism in the mid-jgjunum and enters blood stream via portal circulation. Absorption is regulated by active vitamin D (calcitriol), Factors affect absorption of calcium will affect—in the same manner—the absorption of phosphorus. C. Bady phosphorus: 1. 2. 3. Total body phosphorus is about 800 g. Most of phosphorus (80%) is present in the skeleton (bones and teeth) in the form of hydroxyapatite : 3Ca,(PO)),Ca(OH),, The other 20% is present in other tissues (mostly intracellular) and body fluids. D. Blood phosphorus: 1. ‘Normal plasma inorganic phosphorus: 3-5 mgjdl. 2, Other forms are present:(@) Plasma: Phospholipids, (4) RBCs: Organic phosphate ¢g, ATP, glucose 6-phosphate. E. Factors affecting blood phosphorus: 1, Parathroid hormone: (a) PTH decreases blood phosphorus by stimulating its excretion (through inhibiting its renal tubular reabsorption). 2. Active vitamin D “Calcitriol”: (a) Hypophosphataemia stimulates directly the renal hydroxylation of 25(0H)D, into 1, 25 (GH),D, (calcitriol). (b) Calcitriol increases blood phosphorus through stimulation of: (1) Absorption of phosphorus from the intestine. (2)Bone resorption iz. mobilization of phosphorus from bones. (3) Renal reabsorption by renal tubules. Parathyroids Decreased serum 7 08 5 hosphate £ / I I PO. | \ \ \ * S \ __ Exeretian Oo“ F. Functions of phosphorus: 1. It is found in the structure of bones and teeth. 2. It helps in the formation of the following cellular components: (a) Nucleic acids: DNA, RNAs. (b) Phospholipids: e.g. lecithin, cephalin () Phosphoproteins. (d) Coenzymes: ¢.g, NAD', NADP",opi) text Book of Blochemistry () High energy phosphate compounds eg. ATP, GTP, creatine phosphate, (P) Cyclic AMP and cyclic GMP. (g) Carbohydrate intermediates e.g. glucose-6-phosphate, fructose-1-P. 3. It participates in the formation of blood buffers: G. Exeretion: Mostly (90%) is excreted in urine, H. Requirements: Same as for calcium. [0 MAGNESIUM A, Sources: 1. Leafy green vegetables (containing chlorophyll). B. Absorption: 1. Occurs in the upper small intestine. C. Body magensium: 1. Mostly (70%) in the skeleton (bones and teeth). 2. The remaining 30% is present in the other tissues and body fluids mostly intracellular. D. Blood magnesium: 1. Plasma magnesium: 2-3 mg/dl. 2. RBCs content of magnesium is 3 times greater than plasma. E. Functions: 1. It is found in the structure of skeleton (bones and teeth). 2. It activates many enzymes eg, kinase enzymes. 3. Ik is required for the active transport of other cations (Ca, Na‘, K*) across the cell membrane. 4. It is important for muscle contraction, nerve impulse transmission and it decreases neuromuscular excitability. F,_ Excretion: 1. Mostly (75%) in faeces, G. Requirements: 1. For an adult male (18 years) : 400 mg/day. “Minerals and Water Metabolism cee: A. Sources: 1, The main source of sodium is table salt, ie. salt which is added to prepared food. B. Absorption: 1. It occurs in small intestine (ileum). It is nearly camp!stely absorbed. C. Body sodium: 1, 23 of sodium is present in tissues and body fluids (sodium is the main extracellular cation). 2. About 1/3 of sodium is present in skeleton. D. Plasma sodium: 137 - 145 mEq/L. E. Functions: 1. Maintenance of osmotic pressure and volume of plasma and extracellular fluid. 2. Transmission of nerve impulses. 3, Contraction of muscles. 4, Regulation of acid base balance. G. Excretion: « For adults: 5 g/day. HYPERNATREMIA Nat -> 148 mEq Assess Assess Assess ECF ECF ECF DEPLETED HYPOVOLEMIC NORMAL ISOVOLEMIC EXPANDED HYPERVOLEMIC Loss af H,O + Nat Loss of HO Gain H,0 + Na* (H,0 loss > Na*) A: Diabet ttn Nat gain> H,0 Central Nephrogenic 1. Iatrogenic oo 2, Skin Losses 2. Mineralcortiooids 3, latrogenic Excess ~ Cushing disease. - Adrenal Hyperplasia - Exogenous, too sick | 00 ald, too youngText Book of Blochemistry HYPONATREMIA £130 mEgiL ‘dema ] | | ' ' t Hypovolemic. tsovolemic Hypervotemic nypotonie hypotonic ypatonic ~GHosses -H,0 intoxication ~ Congestive heart + Skin losses + Renal failure failure Lung losses K" losses = Liver damage + Reenal causes = SIADH ‘Cinthosis + Diuretics: ~ Chronic hyponatremia = Nephrosis + Renal damage + Partial urinary Obstruction Precaution: Infusion of sodium > 12mEq/l/day results in osmotic demyelination syndrome I. Toxicity: + Hypertension in susceptible individuals. We A. Sources: 1. Vegetables, fruits and nuts. B. Absorption: + Readily occurs in the small intestine. C. Body potassium: 1. 2/3 of potassium is present in tissues and body fluids (potassium is the main intracellular cation). 2. About 1/3 is present in skeleton. D. Plasma potassium: 35-5 mEq/L. E. Functions: 1. Maintenance of osmotic pressure and volume of intracellular fluid. 2. Transmission of nerve impulses. 3. Contraction of muscles. 4, Regulation of acid base balance. F. Excretion: ° Mainly in urine, G. Requirements: + 4 giday.Minerals and Water Metabolism HYPERKALEMIA > S.SmEq'. Renal Sion-Fenal isntes auetion Moderalolyeducoa Moderately duced in GFR normal GFR or normal GFR. "acute Renal faiure Addison's Disease Primary renal tubular K* “Chronic Renal faaure = Drug induced soeretion ‘ayAmionica -Amlodosis: Wo) Syslesporien = Dstnuctive uropathy {6} Sprorolacione “tonal transplantation {@} Tiamierene Siow ent disoace inadequate Distal + Systemic lupus Delivery of No Erythemaliosis Paeudorypoalsosteronism HYPOKALEMIA Non-enal <35meqt . ee: Marked reduction in GER Moderately recueed | normal GFR ~ Acute myelogenous leukemia ~ Aleohalisi (chronic) Barium salts, soubie = Cholera ~ Dari: iieaiieel of { Giermoea (Bactenal Inf & AIDS) mogaloblastic anemia = Geoshagia - Fail hypokalemia periodic ~ Hot slimate-sneating paralysis = inlestinal Fistula ~ Prolonged hypatherm “Lewin ot = Prolonger hy eof < si = Pancreatic islet tumor- + Vasonctva Peplide-K Secretion “Vomiting - Uratirosigmoidostomy + UreteroileaiostomyText Book of Biochemistry oe HYPOKALEMIA Renal Causes increased BP | ea Low renin High renin 1 . HIGH ALDOSTERONE LOWALDOSTERONE HIGH ALDOSTERONE Aldosterone produeing - Deoxycortisone axcoss = Cushing Syndrome | tumor |11fiHydroxylasa == Ectopic ACTH - Bilateral adrenal H7-cHydroxlase production hyperplasia - Liddle syndrome = High Aldosterone ~ Adrenal Carcinoma Licorice Ingestion = Malignant Hypertension Dexamethazone ~ Renal Artery Stenosis = Renin Producing turrors ~ Hydronephrosis A. Sources: © Table salt ic. salt added to prepared food. B. Absorption: * Readily occurs in small intestine C. Plasma chloride: © 96-106 mEq/L. CSF 120-130 mEq/L. D. Functions: 1. Chloride is the main extracellular anion. Together with sodium, it maintains the osmotic pressure and volume of plasma and extracellular fluid. 2. Chloride ions is essential for formation of HCl in the stomach. 3. Activation of enzymes: Cl activates salivary and pancreatic amylase enzymes E. Excretion: © Mainly in urine. F. Requirements: * For adults: 5 g/day. G. Alterations of plasma chloride: 1. Hyperchloremia (a) Cushing syndrome (b) Respiratory acidosis (©) Renal tubular acidosis (@) DehydrationMinorals and Water Metabolism 2. Hypochloraemia: (decreased plasma chlaride) (a) Results from excessive vomiting. (4) This leads to decrease plasma chloride and increase } sma bicarbonate as compensatory mechanism, causing alkalosis. This type of alkalosis called : hypochloraemic alkalosis. ‘Il. MICROMINERALS (TRACE ELEMENTS) vil ‘A. Sources: 1. Liver, heart, kidney, spleen and fish. 2. Sugarcane syrup (molasses). 3. Dates and egg yolk. 4. . Contrary to popular belief, spinach is a poor source of iron because it is bound ®y to phylate which is difficult to absorb. & B. Absorption: 1. Absorption of iron occurs in the duodenum and the proximal part of intestine, 2. In normal people, about 10-15% of dietiary iron is absorbed. 3. Mechanism: Mucosal block theory : (a) According to this theory, iron is absorbed in the ferrous state (Fe). Inside mucosal cells, it is oxidized to ferric state (Fe) and combines with apoferritin to form ferritin. (0) Ferritin liberates ferrous ions into the capillaries (plasma) and apoferritin is regenerated again. The rate of this liberation depends on body needs. {c) The intestinal content of apoferritin is limited and when all apoferritin molecules become saturated with iron, absorption is blocked ‘Text Book of Biochemistry [Seeines | aera onli I (8.000) | Ingestediron | 10-20 mpidey | | ! ! ! | I | | | I 10-20% “+ sorbed i Fo" Apoterritin Fortin i> Fe 80-90% not absorbed ABSORPTION OF IRON [MUCOSAL BLOCK THEORY] 4. Factors affecting iron absorption: Most of dietary iron is present in the ferric state (Fe"") as a ferric organic compounds. (a) Factors promoting iron absorption: (1) Cooking of food and gastric HCI facilitate the liberation of ferric ions (Fe) from organic compounds. (2)Reducing substances: Vitamin C and cysteine (-SH) of dietary protein help the reducing of ferric ions (Fe“*) into absorbable ferrous (Fe") state. (3) Body needs: Absorption occurs only if the body is in need to iron, More iron is absorbed when there is iron deficiency or when erythropoiesis is increasedMinerals and Water Metabolism cs (8) Factors inhibiting iron absorption: (1) High dietary phosphate and phytate: They form insoluble, non-absorbable organic iron complexes. (2) Steatorrhoea: Where fatty acids form on non-absorbable iron soaps. (3) Alkalies and tea. 5. Recent theory for iron absorption: (a) Iron binds with specific receptors on the brush borders of mucosal cells. (b) It passes inside mucosal cells by active transport system using specific carrier protein. (c) Inside mucosal cells, iron either: (1) Transported through the cell to portal circulation. (2) Incorporated into ferritin formation ie. ferritin acts as storage compound and not as a carrier for iron absorption. y fc Body iron: 1, The total body iron of an adult male is 35 g. 2. It is distributed as follows: RBCs iron (haemoglobin) : 66%, tissue iron (33%) and plasma iron 1%. | Plasma iron 1% Total body ironie Text Book of Blochamistry So 3. RBCs iron (haemoglobin): see haemoglobin metabolism. =— 4. Tissue iron: It includes: (a) Available forms (29 (1) Ferritin: « Contains 23% iron. ive. can be used by tissues when there is body need, + It is the main storage form of iron. « It is formed of a protein called apoferritin which can carry 24 atoms of iron to form ferritin. « It is present in iron stores : liver, spleen, bone marrow and intestine. (2) Hemosiderin: « When body contains very high content of iron more than the capacity of apoferritin, some of iron is found in granules called hemosiderin, «* These granules are composed of iron, protein and polysaccharides. (b) Non-available forms (4%): Can not be used even if there is body needs. All these forms are haemoproteins ie, contain heme ring. (1) Myoglobin: + It is hemoprotein formed of a single heme ring attached to one long polypeptide chain. + It is present in muscles and heart. + It acts as oxygen reserve for quick utilization by contracting muscles, (2) Respiratory cytochromes (b, ¢,, c, a, a): « These are components of respiratory chain in mitochondria. + They act as electron carriers. (3) Catalase and peroxidase: + These are two enzymes that act on the toxic hydrogen peroxide (HQ) converting it into H,0. (4) Tryptophan oxygenase (pyrrolase): * This enzyme is important for tryptophan catabolism. (5) Cytochrome P,,,: « These are a specific group of enzymes that present in liver, lung, Kidney, gut, adrenal cortex, heart and brain. ‘They act as electron carriers. ‘There are two types of cytochrome P,,! Mitochondrial: Which inactivates O, molecules. Microsomal: Mostly present in liver. It acts on toxic fat soluble drugs and xenobiotic agents i.e. foreign chemicals, converting them into water soluble compounds. This helps their excretion,Minerals and Water Metabolism atl NB. The non-available forms conlain a minor amounts of non heme iron in the form of flavoprotein enzymes as NADH dehydrogenase and succinate dehydrogenase, 5. Plasma iron: _(@) Plasma iron: Ranges from 60-160 ug/dl. ©) (8) Transferrin: (1) This is an iron containing glycoprotein synthesized in the liver. (2) Each molecule can carry two atoms of iron in ferric state (Fe). (3) Transferrin may carry up to 180-450 pg iron/dl. This is known as total iron binding capacity (I1KC). (4) This means that only 30% of the TIBC of transferrin is saturated (A). (8)So, TIBC may be defined as—The amount of iron with which plasma (transferrin) can combine. ) (6)In iron deficiency anaemia: plasma iron is decreased, Liver synthesizes more transferrin with subsequent increase of TIBC (B). (7)In liver diseases: both plasma iron and transferrin synthesis tend to decreased (+ Plasma iron and | TIBC) (C). LD) (8)in iron overload: transferrin synthesis is inhibited. This leads to increased \" plasma iron and decreased total iron binding capacity (D). ) (Q Plasma ferritin: (1) Very low concentration of ferritin is present in plasma (Males— 3-30 yg%, Females—3-15 ug%). (2) Measurement of plasma ferritin gives a good idea about body iron stores. (3) A low plasma ferritin indicates the presence of depleted iron stores eg. in iron deficiency anaemia. (4)A raised plasma ferritin is found in iron overload and also in many patients with liver disease and cancer.Text Book of Biochemistry TRANSFERRIN a Normal TI8C TRANSFERRIN |, pias iro ran cetciency anaemia: vee enn tae D ron averoas TIC IN NORMAL GONDITIONAND SOME CISEASES D. Functions of iron: Iron is found in the structure of the following compounds 1, Haemoglobin: Which carries oxygen. 2. Myoglobin: Which stores oxygen. 3. Respiratory enzymes: Which use oxygen, 4. Cytochrome P,, : Which detoxieates drugs and oxygen. E, Transport and storage of plasma iron: 1. Absorbed iron enters in the portal blood in ferrous state (Fe"). 2. In the plasma it is rapidly oxidized to ferric state (Fe). This oxidation is catalyzed by a protein containing copper called: ceruloplasmin.. _, Text Book of Biochemistry _ > TRANSFERRIN VT Normal TIES PPM TRANSFERRIN aaa Plana Hom | Iron ecficioney anomie: tee TRANSFERRIN e u @ ere aces Iron overload IBC IN NORMAL CONDITION AND. SOME DISEASES D. Functions of iron: Iron is found in the structure of the following compoun 1, Haemoglobin: Which carries oxygen. 2. Myoglobin: Which stores oxygen. 3, Respiratory enzymes: Which use oxygen. 4. Cytochrome P,,, : Which detoxicates drugs and oxygen. E, Transport and storage of plasma iron: 1, Absorbed iron enters in the portal blood in ferrous state (Fe). 2, In the plasma it is rapidly oxidized to ferric state (Fe). This oxidation is catalyzed by a protein containing, copper called: ceruloplasmin.Minerals and Water Metabotisan es) 3, Then ferric ions are carried by a transferrin, which is taken mostly by bone marrow to synthesize haemoglobin, 4. Iron, from iron stores (ferritin) can be released into plasma and carried by transferrin to be utilized by bone marrow and other tissues, Loss of blood 2 FERRITIN Ne eacration by kdnoy Oe ee ee ee METABOLISM OF IRON F. Excretion: 1. Iron excreted in the faeces is maily exogenous iz, dietary iron that has not been absorbed. 2. In males, there is an average loss of endogenous iron of about 1 mg/day. It is derived from desquamated cells from skin and the intestinal mucosa. 3. In females, there are additional sources of loss, due to menstruation and pregnancy, 4. Urine contains negligible amount of iron. G. Requirements: 1. Adulls: 10 mg/day. 2. Pregnant and lactating women: 30 mg/day. 3. Menstruation: 18 mg/day.(eee) Text Book of Biochemistry H. ALTERATIONS OF PLASMA IRON: 1, Iron deficiency anaemia: (a) Causes: (1) Deficient intake, (2) Impaired absorption: e.g. steatorrhoea, abdominal surgery: (3) Excessive loss e.g. menstrual loss, gastro-intestinal bleeding, bleeding due to some parasites (anchylastoma). (b) Biochemical changes: (1) Plasma iron is decreased. (2) Plasma TIBC is increased. (3) Plasma ferritin is decreased, Z (4) RBCs show: hypochromic, microcytic cells. (2. Iron overload: (@) Causes: (1) Repeated blood transfusion, (2) Intravenous administration of iron. (3) Hemochromatosis (hemosiderosis, bronze diabetes) () This is a rare hereditary disease characterized by abnormal increase *e of iron absorption. (i) Iron is deposited in the form of haemosiderin in : + Liver : Causing liver cirrhosis. Pancreas: Causing fibrosis and diabetes mellitus. + Skin: Causing bronze discolouration of skin. (b) Biochemical changes: (1) Plasma iron is increased. (2) Plasma TIBC is decreased. (@) Plasma fertin is increased. [vit SS A. Sources: 1. Most diets provide the amount of copper needed per day. 2. The richest sources are : liver, kidney, dried legumes and nuts. B. Absorption: + Mainly occurs in the upper small litestine. C. Body copper: 1. The adult human body contains 100-150 mg of copper.Minerals and Water Metabolism 2. 64 mg (80%) are found in muscles and the remaining present in other tissues. ©Xp. Blood copper: 1. In the plasma: 90 pg/dl. Il is present in association of two proteins : (@) Ceruloplasmin: (85%) A copper binding protein. Each molecule can bind 8 atoms of copper, It acts as ferroxidase enzyme during iron metabolism (Fe* and Fe"), (b) Albumin: (15%) It is loosely bound form of copper. It acts as a carrier for transport of copper in plasma. 2. In red cells: 100’ g/dl It is present in association of the enzyme superoxide dismutase (erythrocuprein) which deals with the toxic free radical superoxide ion 7 (O,) generated during aerobic metabolism) (8, Functions: 1. Copper is essential for: (a) Haemoglobin. synthesis. (b) Bone formation. (c) Maintenance of mylein of the nerves. 2. Copper is essential constituent of several metalloenzymes: (e) Ceruloplasmin: Which oxidizes Fe" into Fe“ in the plasma) (b) Superoxide dismutase: Which eleminates the toxic effect of superoxide ions (Q,)- + Superoxide dismutase is present in RBCs (erythrocuprein), liver (hepatocuprein) and brain (cerebrocuprein). (c) Cytochrome oxidase. 3. Copper activates many enzymes e.g. tyrosinase, uricase and dopamine hydroxylase) F. Excretion: 1. Mainly with bile. 2. Urinary exeretion is minimal due to large molecular weight of ceruloplasmin. G. Requirements: © Adults : 2-3 mg/day. HL. Alterations of plasma copper: 1, Hypercupremia (excess plasma copper and ceruloplasmin): + Ceruloplasmin is considered as acute phase protein ie. its plasma level is increased. in infections and malignancy. 2. Hypocupremia (decreased plasma copper and ceruloplasmin) = Wilson's disease (hepatolenticular degeneration):(tas Text Book of Biochemistry — DIFFERENCE BETWEEN WILSON AND MENKES DISEASES (@ This disease is characterized by accumulation of large amounts of copper (1) Liver causing hepatic cirrhosis, (2)Lenticular nucleus of the brain causing lenticular degeneration with abnormal movement. (3) Cornea: Causing greenish-brown discoloration of the corneal margin which is called: Kayser-Fleischer rings. (4) Kidney causing renal tubular damage which leads to: Increased excretion of copper and ceruloplasmin. This results in low a serum copper and ceruloplasmin (ii) Increased excretion of amino acids. This results in aminoaciduria, (b) The cause of the disease is most probably due to (1) Excessive copper absorption from intestine. (2) Inadequate excretion of copper in bile. Parameter Genetics Onset Tissues affected. Abnormality Clinical symptoms Laboratory diagnosis Drug effect Wilson disease Autosomal recessive Late childhood Liver, brain, kidney Cu incorporation into ceruloplasmin, and Cu exeretion into bile is defective. Hepatolenticular degeneration, late death, Cu and ceruloplasmin Tow, increased urinary Cu® excretion, pencillamine helps to to exerete Cu® by chelation. Menkes disease (Minke’s Kinky hair syn- drome) X-linked recessive. At birth. Except liver, all tissues. Due to deficiency of copper dependent enzymes and Cu* intestinal absorption. Cerebral degeneration and abnormal hair, early death Cu® and ceruloplasmin low increased Cu” in intestine and kidney. No effect of drugs.A. Sources: + Meat, liver, eggs, sea food, milk and whole grain products are good sources. B. Absorption: + Zine absorption occurs mainly in small intestine, especially from the duodenum. C. Body zinc: 1, Zine is essential for growth and reproduction, 2. It plays a role in tissue repair and wound healing. 3. Zine forms a complex with insulin in fi islet cells of the pancreas. This helps crystallization, storage and release of insulin. 4. Zinc is essential component of a number of enzymes ¢g:: (a) Alkaline phosphatase. (®) Carbonic anhydrase. (c) Superoxide dismutase. (d) Carboxypeptidase. 5. Zine is required for mobilization of vitamin A from the liver and subsequently maintain the normal concentration of vitamin A in plasma. F. Requirements: + An adult male: 10-20 mg/day. G. Excretion: + Mainly in faeces (mostly unabsorbed dietary zinc). H, Zine deficiency: Tt causes : 1. Hypogonadism 2. Poor healing of wounds. 3. Poor appetite and retarded growth in children. 4. Liver cirrhosis. IODINE A. Sources: 1. lodized table salt will provide daily body needs. 2. Fish, sea foods and weeds and vegetables grown near seaboard are good sources. B. Absorption: « Occurs mainly from small intestine. C. Body iodine: 1. The adult male body contains about 25-50 mg iodine. 2. It is present in: (a) Thyroid gland (50%): as thyroglobulin, (®) Other tissues and body fluids (50%): as T, and T,Gl Text Book of Blochemistry D, Plasma iodine: 1. Organic iodine: 4-8 g/dl 2. Inorganic iodine: 1-2 g/dl. E. Functions: + The only known function of iodine is the formation of thyroid hormones (T, - T,). F. Excretion: * Mainly (70%) in urine. G. Requirements: + For adult; 100-150 ug/day. H. Deficiency: «It results in thyroid hypertrophy (enlargement) and goiter. xt a ‘A. Selenium is an essential component of the enzyme glutathione peroxidase (GSH-PX) which catalyzes the reaction : 2¢SH + H,0, —S*. esse +2H,0 B. This reaction acts as protective mechanism against the oxidative damage of hydrogen peroxide (H,Q,) and fatty acid hydroperoxide by destroying them: 1. In RBCs, it protect haemoglobin and red cell membranes. 2. In liver, it is important for detoxifying lipid hydroperoxides and prevents necrosis. 3. In lens tissue of the eye, prevents its oxidative damage. C. Deficiency of selenium (GSH-PX) : It causes : 1. Haemolytic anaemia. 2. Liver cirrhosis. 3. Cataract. 4. Cardiomyopathy RDA-50-200 yg. (Keshan Syndrome). EG] MANGANESE ] ‘A. Manganese is essential for: 1, Normal bone structure, 2. Reproduction (spermatogenesis and ovulation). 3. Normal function of the central nervous system. B. Manganese is a component of 1. Pyruvate carboxylase. 2. Superoxide dismutase,Text Book of Biochemistry _—_ D. Plasma iodine: 1, Organic iodine: 4-8 ug/dl 2. Inorganic iodine: 1-2 g/dl. E, Functions: + The only: known function of iodine is the formation of thyroid hormones (T, - T). FE. Excretion: + Mainly (70%) in urine. G. Requirements: «For adult: 100-150 g/day. H. Deficiency: It results in thyroid hypertrophy (enlargement) and goiter. A. Selenium is an essential component of the enzyme glutathione peroxidase (GSH-PX) which catalyzes the reaction : B. This reaction acts as protective mechanism against the oxidative damage of hydrogen peroxide (H,O,) and fatty acid hydroperoxide by destroying them: 1. In RBCs, it protect haemoglobin and red cell membranes. 2. In liver, it is important for detoxifying lipid hydroperoxides and prevents necrosis. 3. In lens tissue of the eye, prevents its oxidative damage. C. Deficiency of selenium (GSH-PX) : It causes 1, Haemolytic anaemia, 2, Liver cirrhosis. 3, Cataract, 4, Cardiomyopathy RDA-50-200 tig. (Keshan Syndrome) a A. Manganese is essential for 1. Normal bone structure. 2. Reproduction (spermatogenesis and ovulation). 3. Normal function of the central nervous system. B, Manganese is a component of: 1. Pyruvate carboxylase, 2, Superoxide dismutase,3. Arginase 4, Isocitrate dehydrogenase C. Manganese activates the arginase. D. RDA : 5-6 mg. Minerals and Water Metabolism e EC) COBALT A. Cobalt is a component of vitamin B,, which is necessary for normal blood cell formation. B. Cobalt gives vitamin B,, its red colour. C. Enzymes requiring vitamin B,, for their activities are: 1. Methylmalonyl CoA mutase. 2. Methyltetrahyc folate oxidoreductase, 3. Homocysteine methyltransferase. 4, Ribonucleotide reductase. D. Deficiency of Vitamin B,, causes pernicious anaemia. Fg CHROMIUM y A. It acts only together with insulin to promote glucose utilization. B. Its deficiency leads to impairment of glucose utilization by tissues. C. Antiatherogenic (LLDL THDL). Ex@gViolYBDENUM ‘A. It is a component of oxidase enzymes eg. xanthine oxidase and aldehyde oxidase. A, It increases the hardness of bones and teeth. B. Its deficiency causes dental caries and osteoporosis. C. Now-a-days, it is supplied in drinking water. D. Excess flouride leads to fluorosis : mottling and discolouration of the enamel of teeth and changes in bones. E. RDA: <2 ppm. LYE WATER METABOLISM A. Functions of watet: Water is the most abundant compound in living cells, which usually constitutes about 60% of adult body weight.' itu Text Book of Biochemistry Tt has the following functions : Water is a solvent for many ionic compounds and neutral molecules. Vater is important to maintain the structure and functions of macromolecules of cells vg. proteins and polynuclegtides. Regulation of body temperature by evaporating the moisture in the lungs and from the skin. 4, Water is the main constituent of all body fluids. B. Total body water Total body water is distributed between two main compartments; 1. Intracellular fluid : This is the fluid within body cells. It constitutes about 40% of total body weight, and 2/3 of total body water. 2. Extracellular fluid ; This is all the fluids outside the body cells. It constitutes about 20% of total body weight and 1/3 of total body water, Extracellular fluid can be subdivided into (a) Plasma. (®) Interstitial and lymph fluid. (©) Transcellular fluids : These are fluids present inside organs as liver, salivary glands, mucous membranes of the respiratory and gastrointestinal tract. It also includes fluids in spaces within the eye, CSF and other body fluids. {d) Bones, dense connective tissue and cartilage : Because of relative avascularity, these tissues do not exchange fluid or electrolytes with plasma and classified as subdivision of extracellular fluid, C. Water balance: It means that water intake is equal to water loss. 1. Water intake : Water is derived from : » (@ Drinking water and other liquids 1400 mi/day. (b) Solid foods (approximately, 80% of normal 800 ml/day. diet consists of water) (€) Metabolic water (derived from oxidation of 300 mi/day. organic food inside the cells) 2500 mi/day. 2. Water loss : Water is lost from the body through four routes * (a) Skin : Sensible (sweat) and insensible perspiration, 850 ml/day. (b) Lungs : Water vapour in the expiration. () Kidneys : Urine 1500 ml/day. (d) Intestine : Feces. 150 mi/day. 2300 mi/day. 3. In very hot weather, or during periods of prolonged heavy exercise, water loss in sweat my increase up to 3000 ml/hour, which could deplete the body water rapidly. 4. Additional water losses in diseases : (@) In kidney diseases, in which concentrating ability is limited.Minerals and Water Metabolism ee (®) Diarrhoea and vomiting especially in infants {c) Fevers due to excessive sweating, (d) Individuals subjected to high environmental temperature. Disturbance of water balance: Inspite of large amount of water content (60% of adult body weight), there is no water reserve in the body. Loss of 5% of body water making the subject thirst, loss of 10% making him very ill and he will die if losses 20% of total body water. (a) Dehydration is the increase of water loss than water intake. It may be due to pure water loss or electrolyte deficit: (1) Water loss (Hypertonic dehydratis wi Causes: Restriction of water supply for any reason, or when the losses are excessive, Metabolic disturbances : The water loss exceeds the rate of electrolyte loss. The extracellular fluid becomes concentrated and hypertonic to the cell. Water then shifts from the cells to the extracellular space to compensate, creating what is called : intracellular dehydration. Symptoms: The patient becomes progressively weaker, but he does not complaint of thirst and his urine volume is not markdly changed. Treatment: Extracellular dehydration is corrected by giving water and electrolytes (saline) intravenously until symptoms disappear and urine volume is restored. (2) Electrolyte deficit (Hypotonic dehydration): Causes: This condition results when water and electrolyte loss is corrected by giving water only. This will lead to a deficiency of electrolytes in the presence of normal or excess total body water. Metabolic disturbance: The deficiency of sodium in extracellular fluid results in hypotoicity of this fluid compartment so, some water passes into the cells, which are hypertonic to the extracellular fluid, causing the so-called ; intracellular edema. This will lead to diminution in extracellular fluid volume with decrease in blood volume, fall in blood pressure, and consequent impairment in renal function. Symptoms: The patient becomes progresseively weaker, but he does not complaint of thirst and his urine volume is not markedly changed. ‘Treatment; Extracellular dehydration is corrected by giving water and electrolytes ( saline ) intravenously.(ied Text Book of Biochemistry ORIGIN OF WORDS é Hypertonic (Greek) Hyper-above, Tenos-Tension Hypotonic (Greek) Hypo-Below, Tonos-Tension Tsotonic (Greek) Iso-Equa, Tonos-Tension Ceruloplasmin (Latin) Caeruleus-Blue eee Rel Calcitonin Calcitriol Manganese Magnesium Hemosiderosis Hemochromatosis It is peptide hormone secreted by thyroid gland and functions at hypocaleemic agent. It is an active form of D, secreted by kidney and functions as hypercalcemic agent Tt is a trace element and RDA is 5-6 mg. It is macro element and RDA is 400 mg. It is an excessive iron accumulation in tissues (spleen and liver) due to secondary causes like high iron-low phosphorus diets, tepeated blood transfusions, hereditary hemolytic anemias and thalassemias. It is an excessive iron accumulation in tissues like spleen, liver, pancreas, joints and skin caused by excessive intestinal iron absorption due to genetic disorder.