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CHAPTER 28 Plasma Proteins Chapter at a Glance The reader will be able to answer questions on the following topics: ¾¾Plasma proteins ¾¾Electrophoresis ¾¾Albumin, functions, clinical significance ¾¾Hypoalbuminemia ¾¾Globulins, alpha, beta, gamma Total blood volume is about 4.5 to liters in adult human being If blood is mixed with an anticoagulant and centrifuged, the cell components (RBC and WBC) are precipitated The supernatant is called plasma About 55–60% of blood is made up of plasma i If blood is withdrawn without anticoagulant and allowed to clot, after about hours liquid portion is separated from the clot This defibrinated plasma is called serum, which lacks coagulation factors including prothrombin and fibrinogen ii Total protein content of normal plasma is to g/100 mL iii The plasma proteins consist of albumin (3.5 to g/dL), globulins (2.5 – 3.5 g/dL) and fibrinogen (200– 400 mg/dL) The albumin : globulin ratio is usually between 1.2:1 to 1.5:1 iv Almost all plasma proteins, except immunoglobulins are synthesized in liver Plasma proteins are generally synthesized on membrane-bound polyribosomes Most plasma proteins are glycoproteins ¾¾Transport proteins in blood ¾¾Acute phase proteins in blood ¾¾Ceruloplasmin ¾¾Alpha-1 antitrypsin ¾¾Clotting factors v In laboratory, separation can be done by salts Thus, fibrinogen is precipitated by 10% and globulins by 22% concentration of sodium sulfate Ammonium sulfate will precipitate globulins at half saturation and albumin at full saturation vi In clinical laboratory, total proteins in serum or plasma of patients are estimated by Biuret method (see Chapter 4) Albumin is quantitated by Bromo cresol green (BCG) method, in which the dye is preferentially bound with albumin, and the color is estimated colorimetrically ELECTROPHORESIS In clinical laboratory, electrophoresis is employed regularly for separation of serum proteins The term electrophoresis refers to the movement of charged particles through an electrolyte when subjected to an electric field The details are given in Chapter 35 Normal and abnormal electrophoretic patterns are shown in Figures 28.1 and 28.2 Chapter 28: Plasma Proteins 379 Normal Patterns and Interpretations Abnormal Patterns in Clinical Diseases i In agar gel electrophoresis, normal serum is separated into bands Their relative concentrations are given below: Albumin : 55–65% Alpha-1 globulin : 2–4% Alpha-2 globulin : 6–12% Beta globulin : 8–12% Gamma globulin : 12–22% ii Albumin has the maximum and gamma globulin has the minimum mobility in the electrical field iii G a m m a g l o b u l i n s c o n t a i n t h e a n t i b o d i e s (immunoglobulins) Most of the alpha-1 fraction is made up of alpha-1 antitrypsin Alpha-2 band is mainly made up by alpha-2 macroglobulin Beta fraction contains low density lipoproteins Various abnormalities can be identified in the electrophoretic pattern (Figs 28.1A and B) Chronic infections: The gamma globulins are increased, but the increase is smooth and widebased Multiple myeloma: In para-proteinemias, a sharp spike is noted and is termed as M-band This is due to monoclonal origin of immunoglobulins in multiple myeloma (Fig 28.2) Fibrinogen: Instead of serum, if plasma is used for electrophoresis, the fibrinogen will form a prominent band in the gamma region, which may be confused with the M-band Primary immune deficiency: The gamma globulin fraction is reduced Nephrotic syndrome: All proteins except very big molecules are lost through urine, and so alpha-2 fraction (containing macroglobulin) will be very prominent Cirrhosis of liver: Albumin synthesis by liver is decreased, with a compensatory excess synthesis of globulins by reticuloendothelial system So albumin band will be thin, with a wide beta fraction; sometimes beta and gamma fractions are fused Fig 28.1A: Serum electrophoretic patterns = Normal pattern; = Multiple myeloma (M band) between b and g region; =Chronic infection, broad based increase in g region; general increase in a1 and a2 bands; = Nephrotic syndrome; hypoalbuminemia; prominent a2 band; = Cirrhosis of liver; decreased albumin; = Plasma showing fibrinogen (normal condition) This may be mistaken for paraproteins Fig 28.1B: Serum electrophoretic patterns 380 Textbook of Biochemistry Chronic lymphatic leukemia, gamma globulin fraction is reduced Alpha-1 antitrypsin deficiency: The alpha-1 band is thin or even missing ALBUMIN i The name is derived from the white precipitate formed when egg is boiled (Latin, albus = white) Albumin constitutes the major part of plasma proteins ii It has one polypeptide chain with 585 amino acids It has a molecular weight of 69,000 D It is elliptical in shape iii It is synthesized by hepatocytes; therefore, estimation of albumin is a liver function test (see Chapter 26) Albumin is synthesized as a precursor, and the signal peptide is removed as it passes through endoplasmic reticulum iv Albumin can come out of vascular compartment So albumin is present in CSF and interstitial fluid v Half-life of albumin is about 20 days Liver produces about 12 g of albumin per day, representing about 25% of total hepatic protein synthesis Half-life: Each plasma protein has a characteristic half-life in circulation; e.g half-life of albumin is 20 days, and that of haptoglobin is days The half-life is studied by labeling the pure protein with radioactive chromium (51Cr) A known quantity of the labeled protein is injected into a normal person, and blood samples are taken at different time intervals Half-life of a protein in circulation may be drastically reduced when proteins are lost in conditions, such as Crohn's disease (regional ileitis) or protein losing enteropathy Fig 28.2: Normal and abnormal electrophoretic patterns Functions of Albumin Colloid Osmotic Pressure of Plasma i The total osmolality of serum is 278–305 mosmol/kg (about 5000 mm of Hg) But this is produced mainly by salts, which can pass easily from intravascular to extravascular space Therefore, the osmotic pressure exerted by electrolytes inside and outside the vascular compartments will cancel each other But proteins cannot easily escape out of blood vessels, and therefore, proteins exert the ‘effective osmotic pressure' It is about 25 mm Hg, and 80% of it is contributed by albumin The maintenance of blood volume is dependent on this effective osmotic pressure ii According to Starling's hypothesis, at the capillary end, the blood pressure (BP) or hydrostatic pressure expels water out, and effective osmotic pressure (EOP) takes water into the vascular compartment (Fig 28.3) iii At arterial end of the capillary, BP is 35 mm Hg and EOP is 25 mm; thus water is expelled by a pressure of 10 mm Hg At the venous end of the capillary, EOP is 25 mm and BP is 15 mm, and therefore water is imbibed with a pressure of 10 mm Thus, the number of water molecules escaping out at arterial side will be exactly equal to those returned at the venous side and therefore blood volume remains the same iv If protein concentration in serum is reduced, the EOP is correspondingly decreased Then return of water into blood vessels is diminished, leading to accumulation of water in tissues This is called edema Chapter 28: Plasma Proteins 381 v Edema is seen in conditions where albumin level in blood is less than g/dL (see hypoalbuminemia) Clinical Applications Transport Function Albumin-fatty acid complex cannot cross blood-brain barrier and hence fatty acids cannot be taken up by brain The bilirubin from albumin may be competitively replaced by drugs like aspirin Being lipophilic, unconjugated bilirubin can cross the blood brain barrier and get deposited in brain The brain of young children are susceptible; free bilirubin deposited in brain leads to kernicterus and mental retardation (see Chapter 21) Albumin is the carrier of various hydrophobic substances in the blood Being a watery medium, blood cannot solubilize lipid components i Bilirubin and non-esterified fatty acids are specifically transported by albumin ii Drugs (sulfa, aspirin, salicylate, dicoumarol, phenytoin) iii Hormones: Steroid hormones, thyroxine iv Metals: Albumin transports copper Calcium and heavy metals are non-specifically carried by albumin Only the unbound fraction of drugs is biologically active Buffering Action All proteins have buffering capacity Because of its high concentration in blood, albumin has maximum buffering capacity (see Chapter 29) Albumin has a total of 16 histidine residues which contribute to this buffering action Nutritional Function All tissue cells can take up albumin by pinocytosis It is then broken down to amino acid level So albumin may be considered as the transport form of essential amino acids from liver to extrahepatic cells Human albumin is clinically useful in treatment of liver diseases, hemorrhage, shock and burns Blood Brain Barrier Drug Interactions When two drugs having high affinity to albumin are administered together, there may be competition for the available sites, with consequent displacement of one drug Such an effect may lead to clinically significant drug interactions, e.g phenytoin-dicoumarol interaction Protein-bound Calcium Calcium level in blood is lowered in hypoalbuminemia Thus, even though total calcium level in blood is lowered, ionized calcium level may be normal, and so tetany may not occur (see Chapter 39) Calcium is lowered by 0.8 mg/dL for a fall of g/dL of Albumin Therapeutic Use Human albumin is therapeutically useful to treat burns, hemorrhage and shock Edema Hypoalbuminemia will result in tissue edema (see Starling's law) Fig 28.3: Starling hypothesis a Malnutrition, where albumin synthesis is depressed (generalized edema) b Nephrotic syndrome, where albumin is lost through urine (facial edema) c Cirrhosis of liver (mainly ascites), where albumin synthesis is less and it escapes into ascitic fluid d Chronic congestive cardiac failure: Venous congestion will cause increased hydrostatic pressure and decreased return of water into capillaries and so pitting edema of feet may result 382 Textbook of Biochemistry Normal Value Chronic Infections Normal level of Albumin is 3.5–5 g/dL Lowered level of albumin (hypoalbuminemia) has important clinical significance Gamma globulins are increased, but the increase is smooth and wide based (Fig 28.1A) Hypoalbuminemia a Cirrhosis of liver: Synthesis is decreased b Malnutrition: Availability of amino acids is reduced and albumin synthesis is affected c Nephrotic syndrome: Permeability of kidney glomerular membrane is defective, so that albumin is excreted in large quantities d Albuminuria: Presence of albumin in urine is called albuminuria It is always pathological Large quantities (a few grams per day) of albumin is lost in urine in nephrotic syndrome Small quantities are lost in urine in acute nephritis, and other inflammatory conditions of urinary tract Detection of albumin in urine is done by heat and acetic acid test (see Chapter 27) In microalbuminuria or minimal albuminuria or paucialbuminuria, small quantity of albumin (30–300 mg/d) is seen in urine (Paucity = small in quantity) e Protein losing enteropathy : Large quantities of albumin is lost from intestinal tract f Analbuminemia is a very rare condition, where defective mutation in the gene is responsible for absence of synthesis Albumin-Globulin Ratio In hypoalbuminemia, there will be a compensatory increase in globulins which are synthesized by the reticuloendothelial system Albumin-globulin ratio (A/G ratio) is thus altered or even reversed This again leads to edema Hypoproteinemia Since albumin is the major protein present in the blood, any condition causing lowering of albumin will lead to reduced total proteins in blood (hypoproteinemia) Hypergammaglobulinemias Low Albumin Level When albumin level is decreased, body tries to compensate by increasing the production of globulins from reticuloendothelial system Multiple Myeloma Drastic increase in globulins are seen in para-proteinemias, when a sharp spike is noted in electrophoresis This is termed as M-band because of the monoclonal origin of immunoglobulins (Figs 28.1B and 28.2) The monoclonal origin of immunoglobulins is seen in multiple myeloma (see Chapter 55) Monoclonal gammopathies are characterized by the presence of a monoclonal protein, which can be detected by serum protein electrophoresis and typed by immunofixation electrophoresis.The light chains are produced in excess which is excreted in urine as Bence Jones proteins (BJP) when their serum level increases Multiple myeloma is the most common type of monoclonal gammopathy Free light chain assay along with kappa and lambda ratio in serum and urine is found to be very useful in early diagnosis, monitoring the response to treatment and prediction of prognosis TRANSPORT PROTEINS Blood is a watery medium; so lipids and lipid soluble substances will not easily dissolve in the aqueous medium of blood Hence such molecules are carried by specific carrier proteins Their important features are summarized in Table 28.1 Albumin : It is an important transport protein, which carries bilirubin, free fatty acids, calcium and drugs (see above) Pre-albumin or Transthyretin: It is so named because of its faster mobility in electrophoresis than albumin It is more appropriately named as Transthyretin or Thyroxin binding pre-albumin (TBPA), because it carries thyroid hormones, thyroxin (T4) and tri-iodo thyronine (T3) Its half-life in plasma is only day Retinol binding protein (RBP) : It carries vitamin A (see Chapter 36) It is a low molecular weight protein, and so is liable to be lost in urine To prevent this loss, RBP is attached to pre-albumin; the complex is large and will not pass through kidney glomeruli It is a negative acute phase protein Thyroxine binding globulin (TBG) : It is the specific carrier molecule for thyroxine and tri-iodo thyronine TBG level is increased in pregnancy; but decreased in nephrotic syndrome Chapter 28: Plasma Proteins 383 TABLE 28.1: Carrier proteins or transport proteins of plasma Name Plasma level Molecular wt (Dalton ) Compound bound or transported Electrophoretic mobility Biological and clinical significance Albumin 3.5–5 g/dL 69,000 Fatty acids, bilirubin, calcium, thyroxine, heavy metals, drugs e.g aspirin, sulfa Maximum anodal migration Bilirubin competes with aspirin for binding sites on albumin Prealbumin (Transthyretin) 25–30 mg/ dL 54,000 Steroid hormones, thyroxine, retinol Faster than albumin Rich in tryptophan Half-life is 1day It is a negative acute phase protein Transports T3 and T4 losely Retinol binding protein (RBP) 3–6 mg/dL 21,000 Retinol (Vitamin A) a1 Synthesized by liver RBP has a short half-life Level indicates vitamin A status Useful to assess the protein turn over rate Thyroxine binding globulin (TBG) 1–2 mg/dL 58,000 Thyroxine a1 Assessment of the binding sites on TBG is important in studying thyroid function It is synthesized in liver Transcortin; Cortisol binding globulin (CBG) 3–3.5 mg/ dL 52,000 Cortisol and Corticosterone a1 Synthesized by liver Increased in pregnancy Free unbound fraction of hormone is biologically active Haptoglobin (Hp) 40-175 mg/ 100,000 dL to 400,000 Hemoglobin a2 Synthesized in liver Low level indicates hemolysis Half-life of Hp is days; but that of Hb-Hp is only 90 minutes It is an acute phase protein (see Chapter 35) Transferrin 200–300 mg/dL 76,500 Iron 33% saturated b Conserves iron by preventing iron loss through urine (see Chapter 35) Hemopexin 50–100 mg/dL 57,000 Free heme b Helps in preventing loss of heme (and so iron also) from body (see Chapter 35) Transcortin: It is also known as Cortisol binding globulin (CBG) It is the transport protein for cortisol and corticosterone Haptoglobin: Haptoglobin (for hemoglobin), Hemopexin (for heme) and Transferrin (for iron) are important to prevent loss of iron from body Polymorphism The term polymorphism is applied when the protein exists in different phenotypes in the population; but only one form is seen in a particular person Haptoglobin, transferrin, ceruloplasmin, alpha-1-antitrypsin and immunoglobulins exhibit polymorphism For example, Haptoglobin (Hp) exists in three forms, Hp1–1, Hp2–1, and Hp2–2 Two genes, designated Hp1 and Hp2 are responsible for these polymorphic forms Their functional capabilities are the same These polymorphic forms are recognized by electrophoresis or by immunological analysis Study of polymorphism is useful for genetic and anthropological studies ACUTE PHASE PROTEINS The level of certain proteins in blood may increase 50 to 1000 folds in various inflammatory and neoplastic conditions Such proteins are acute phase proteins Important acute phase proteins are described below: C-Reactive Protein (CRP) So named because it reacts with C-polysaccharide of capsule of pneumococci CRP is a beta-globulin and has a molecular weight of 115–140 kD It is synthesized in liver It can stimulate complement activity and macrophage phagocytosis When the inflammation has subsided, CRP quickly falls, followed by ESR (erythrocyte sedimentation rate) CRP level, especially high sensitivity C-reactive 384 Textbook of Biochemistry protein level in blood has a positive correlation in predicting the risk of coronary artery diseases (see Chapter 25) Ceruloplasmin i Ceruloplasmin is blue in color (Latin, caeruleus=blue) It is an alpha-2 globulin with molecular weight of 160,000 Daltons It contains to copper atoms per molecule ii Ceruloplasmin is mainly synthesized by the hepatic parenchymal cells and a small portion by lymphocytes and macrophages After the formation of peptide part (apo-Cp) copper is added by an intracellular ATPase and carbohydrate side chains are added to make it a glycoprotein (holo-Cp) The normal plasma half-life of holo-Cp is 4–5 days iii Ceruloplasmin is also called Ferroxidase, an enzyme which helps in the incorporation of iron into transferrin (see Chapter 39) It is an important antioxidant in plasma iv About 90% of copper content of plasma is bound with ceruloplasmin, and 10% with albumin Copper is bound with albumin loosely, and so easily exchanged with tissues Hence, transport protein for copper is Albumin v Lowered level of ceruloplasmin is seen in Wilson's disease, malnutrition, nephrosis, and cirrhosis vi Ceruloplasmin is an acute phase protein Increased plasma Cp levels are seen in active hepatitis, biliary cirrhosis, hemochromatosis, and obstructive biliary disease, pregnancy, estrogen therapy, inflammatory conditions, collagen disorders and in malignancies Drugs increasing the ceruloplasmin level are, estrogen and contraceptives Reference blood levels of ceruloplasmin are: Adults Males 22 – 40 mg/dL Females 25 – 60 mg/dL Pregnancy 30 – 120 mg/dL Wilson's Disease a Level is reduced to less than 20 mg/dL in Wilson's hepatolenticular degeneration It is an inherited autosomal recessive condition Incidence of the disease is in 50,000 b The basic defect is a mutation in a gene encoding a copper binding ATPase in cells, which is required for excretion of copper from cells So, copper is not excreted through bile, and hence copper toxicity Please also see Chapter 39, under copper metabolism c Increased copper content in hepatocyte inhibits the incorporation of copper to apo-ceruloplasmin So ceruloplasmin level in blood is decreased Clinical Features a Accumulation in liver leads to hepatocellular degeneration and cirrhosis b Deposits in brain basal ganglia leads to lenticular degeneration and neurological symptoms c Copper deposits as green or golden pigmented ring around cornea; this is called Kayser-Fleischer ring d Treatment consists of a diet containing low copper and injection of D-penicillamine, which excretes copper through urine Since zinc decreases copper absorption, zinc is useful in therapy Alpha-1 Antitrypsin (AAT) It is otherwise called alpha-anti-proteinase or protease inhibitor It inhibits all serine proteases (proteolytic enzymes having a serine at their active center), such as plasmin, thrombin, trypsin, chymotrypsin, elastase, and cathepsin Serine protease inhibitors are abbreviated as Serpins The AAT is synthesized in liver It is a glycoprotein with a molecular weight of 50 KD It forms the bulk of molecules in serum having alpha-1 mobility Normal serum level is 75 – 200 mg/dL AAT deficiency causes the following conditions: Emphysema: The incidence of AAT deficiency is in 1000 in Europe, but uncommon in Asia The total activity of AAT is reduced in these individuals Bacterial infections in lung attract macrophages which release elastase In the AAT deficiency, unopposed action of elastase will cause damage to lung tissue, leading to emphysema About 5% of emphysema cases are due to AAT deficiency Nephrotic syndrome: AAT molecules are lost in urine, and so AAT deficiency is produced Liver Cirrhosis Deficiency of a1 antitrypsin is the most common genetic cause for liver disease in infants and children It starts as “neonatal hepatitis syndrome” and may progress to liver failure and cirrhosis a1 antitrypsin can be detected by serum electrophoresis Chapter 28: Plasma Proteins Alpha-2 Macroglobulin (AMG) It is a tetrameric protein with molecular weight of 725 KD It is the major component of alpha-2 globulins It is synthesized by hepatocytes and macrophages AMG inactivates all proteases, and is an important in vivo anti-coagulant AMG is the carrier of many growth factors, such as platelet derived growth factor (PDGF) Normal serum level is 130–300 mg/ dL Its concentration is markedly increased (up to –3 g/dL) in Nephrotic syndrome, where other proteins are lost through urine Negative Acute Phase Proteins During an inflammatory response, some proteins are seen to be decreased in blood; those are called negative acute phase proteins Examples are albumin, transthyretin (prealbumin), retinol binding protein and transferrin Transferrin is a specific iron binding protein (see Chapter 39) It has a half-life of 7–10 days and is used as a better index of protein turnover than albumin Plasma contains many enzymes (see Chapter 23), protein hormones (see Chapter 50) and immunoglobulins (see Chapter 55) A comprehensive list of normal values for the substances present in blood is given in the Appendix II CLOTTING FACTORS The word coagulation is derived from the Greek term, "coagulare" = to curdle The biochemical mechanism of clotting is a typical example of cascade activation The coagulation factors are present in circulation as inactive zymogen forms They are converted to their active forms only when the clotting process is initiated This would prevent unnecessary intravascular coagulation Activation process leads to a cascade amplification effect, in which one molecule of preceding factor activates 1000 molecules of the next factor Thus within seconds, a large number of molecules of final factors are activated The clotting process is schematically represented in Figure 28.4 and the characteristics of coagulation factors are shown in Table 28.2 Several of these factors require calcium for their activation The calcium ions are chelated by the gamma carboxyl group of glutamic acid residues of the factors, prothrombin, VII, IX, X, XI and XII The gamma carboxylation of glutamic acid residues is dependent on vitamin K (see Chapter 33), and occurs after synthesis of the protein (post-translational modification) Prothrombin It is a single chain zymogen with a molecular weight of 69,000 D The plasma concentration is 10–15 mg/dL The 385 prothrombin is converted to thrombin by Factor Xa, by the removal of N-terminal fragment Thrombin It is a serine protease with molecular weight of 34,000 D The Ca++ binding of prothrombin is essential for anchoring the prothrombin on the surface of platelets When the terminal fragment is cleaved off, the calcium binding sites are removed and so, thrombin is released from the platelet surface Fibrinogen The conversion of fibrinogen to fibrin occurs by cleaving of Arg-Gly peptide bonds of fibrinogen Fibrinogen has a molecular weight of 340,000 D and is synthesised by the liver Normal fibrinogen level in blood is 200–400 mg/ dL The fibrin monomers formed are insoluble They align themselves lengthwise, aggregate and precipitate to form the clot Fibrinogen is an acute phase protein Fibrinolysis Unwanted fibrin clots are continuously dissolved in vivo by Plasmin, a serine protease Its inactive precursor is plasminogen (90 kD) It is cleaved into two parts to produce the active plasmin Plasmin in turn, is inactivated by alpha-2 antiplasmin Tissue plasminogen activator (TPA) is a serine protease present in vascular endothelium TPA is released during injury and then binds to fibrin clots Then TPA cleaves plasminogen to generate plasmin, which dissolves the clots Urokinase is another activator of plasminogen Urokinase is so named because it was first isolated from urine Urokinase is produced by macrophages, monocytes and fibroblasts Streptokinase, isolated from streptococci is another fibrinolytic agent Clinical Significance Thrombosis in coronary artery is the major cause of myocardial infarction (heart attack) If TPA, urokinase or streptokinase is injected intravenously in the early phase of thrombosis, the clot may be dissolved and recovery of patient is possible Prothrombin Time (PT) It evaluates the extrinsic coagulation pathway, so that if any of the factors synthesized by the liver (factors I, II, V, VII,IX and X) is deficient prothrombin time will be prolonged It is the time required for the clotting of whole blood (citrated or oxalated) after addition of calcium and tissue thromboplastin So, fibrinogen is polymerized to fibrin by thrombin It is commonly assessed by the “one stage prothrombin time of Quick” (named after the inventor) The results are expressed either in seconds or as a ratio of the plasma prothrombin time to a control plasma time The normal 386 Textbook of Biochemistry control PT is – 11 seconds A prolongation of seconds is considered as abnormal Values more than 14 seconds indicate impending hemorrhage The PT is prolonged if any of the concerned factors are deficient The present techniques express the prothrombin level as a ratio as INR (Internationalized ratio) Liver dysfunction of acute onset will be reflected as prolonged prothrombin time Out of 13 clotting factors, 11 are synthesized by the liver Their synthesis is dependent on availability of vitamin K and normal hepatocellular function Prolonged PT may be the initial supportive laboratory parameter to diagnose an acute liver disease Persistent and progressing prolonged PT is suggestive of fulminant liver failure PT measurements are useful to differentiate cholestasis and severe hepatocellular disease When prolonged PT result is obtained; give vitamin K by intramuscular injection and after hours recheck PT If the PT becomes normal after vitamin K injection (which is needed for post-translational modification of prothrombin) the diagnosis of cholestasis can be made If the PT is prolonged, the possibility is severe hepatocellular disease ABNORMALITIES IN COAGULATION Hemophilia A (Classical Hemophilia) This is an inherited X-linked recessive disease affecting males and transmitted by females Male children of hemophilia patients are not affected; but female children will be carriers, who transmit the disease to their male offspring (Fig 28.5) This is due to the deficiency of factor VIII (anti hemophilic globulin) (AHG) It is the commonest of the inherited coagulation defects There will be prolongation of clotting time Hence, even trivial wounds, such as tooth extraction will cause excessive loss of blood Patients are prone to internal bleeding into joints and intestinal tract Until recently the treatment consisted of administration of AHG, prepared from pooled sera every months Since this was not generally available, the usual treatment was to transfuse blood periodically, which may lead to eventual iron overload, hemochromatosis (see Chapter 39) Several hemophilia patients, receiving repeated transfusions became innocent victims of AIDS Pure AHG is now being produced by recombinant technology and is the treatment of choice Hemophilia B or Christmas Disease It is due to factor IX deficiency The Christmas disease is named after the first patient reported with this disease Similar deficiencies of factors X and XI are also reported In these diseases, the manifestations will be similar to classical hemophilia Other Disorders Acquired hypofibrinogenemia or afibrinogenemia may occur as a complication of premature separation of placenta or abruptio placenta TABLE 28.2: Factors involved in coagulation process No Name Molecular weight (Daltons) Electrophoretic mobility Activated by Function I Fibrinogen 340,000 b and g Thrombin Forms the clot (fibrin) II Prothrombin 69,000 a2 Factor Xa Activation of fibrinogen and factors XIII, VIII and V IV Calcium — Activation of factor II, VII, IX, X,XI and XII V Labile factor 200,000 Thrombin Binding of prothrombin to platelet VII Proconvertin; serum prothrombin convertin antecedent (SPCA) 45,500 Thrombin Activation of factor X VIII Antihemophilic globulin (AHG) 1,200,000 b2 Thrombin Activation of factor X IX Plasma thromboplastincomponent (PTC); Christmas factor 62,000 a Factor Xla Activation of factor X X Stuart Prower factor 59,000 a Factor IXa Activation of prothrombin XI Plasma thromboplastin anticedent (PTA) 200,000 bg Factor XIIa Activation of factor IX XII Hageman factor 80,000 Kallikrein Activation of factor XI XIII Fibrin stabilizing factor (Liki Lorand factor) 320,000 Thrombin Stabilization of fibrin clot by forming cross links Prekallikrein 85,000 bg g Activation of factor XII Chapter 28: Plasma Proteins Proteolytic thromboplastic substances may enter from placenta to maternal circulation which set off the clotting cascade (disseminated intravascular coagulation or DIC) But the clots are usually degraded immediately by plasminolysis Continuation of this process leads to removal of all available prothrombin and fibrinogen molecules leading to profuse postpartum hemorrhage In some cases of carcinoma of pancreas, trypsin is released into circulation leading to intravascular coagulation This may be manifested as fleeting thrombophlebitis Trousseau diagnosed his own fatal disease as cancer of pancreas when he developed thrombophlebitis The combination of carcinoma of pancreas, migratory thrombophlebitis and consumption coagulopathy is termed as Trousseau's triad Prothrombin G20210A Polymorphism Another hereditary thrombophilia, the G20210A polymorphism in the prothrombin gene elevates the plasma concentrations of prothrombin (FII) without changing the amino acid sequence of the protein Patients Fig 28.4: Cascade pathway of coagulation 387 with this mutation have PT and aPTT results that fall within the normal range, as well as normal functional clot-based studies DNA studies will show a G-to-A substitution in the 3’-untranslated region of prothrombin gene at nucleotide 20210 Protein C and S Deficiency These two vitamin K-dependent factors interrupt the activity of clotting factors V and VIII Activated protein C is a proteolytic enzyme, while protein S is an essential co-factor Antithrombin Deficiency AT, formerly called AT III, is a vitamin K-independent glycoprotein that is a major inhibitor of thrombin and other coagulation serine proteases, including factors Xa and IXa AT forms a competitive 1:1 complex with its target but only in the presence of a negatively charged glycosaminoglycan, such as heparin or heparin sulfate Patients with AT deficiency will have little AT III activity as measured in a chromogenic assay Index Hyaluronic acid 80, 145 Hybrid cells 640 Hybridoma 98 Hydrochloric acid 550 secretion 356f Hydrogen 735 bonding 5, 575 peroxide 185, 257, 434, 566 Hydrolases 49 Hydrolysis 546, 673 of DNA 586 of starch 78 of triacylglycerols 88 of triglycerides 88f Hydroperoxidases 258 Hydrophobic interaction 6, 6f Hydroxyamino acids 24, 25f Hydroxycobalamin 492 Hydroxyeicosatetraenoic acid 191f Hydroxyfatty acids 85 Hydroxyindoleacetic acid 239 Hydroxylases 258 Hydroxylation of proline and lysine 497 Hydroxyproline 244 Hydroxypyruvate 214 Hyperammonemia 205, 207, 208f hyperornithinemia homocitrullinuria syndrome 208 Hyperargininemia 206 Hyperbilirubinemia 278, 279 Hypercalcemia 401, 507, 508, 512 Hyperchloremic acidosis 400, 401, 507 Hyperemesis 165 Hypergammaglobulinemia 382, 691 Hyperglycemia 313, 326, 412 Hyperglycemic glucosuria 317 hormone 313, 322 Hyperhomocysteinemia 221, 222, 490 Hyperhydroxyprolinemia 244 Hyperkalemia 397, 402, 415 Hyperkalemic periodic paralysis 416 Hyperkeratosis 468 Hyperlipidemias 326, 334, 342 Hyperlipoproteinemia 343 Hyperlysinemias 226 Hypermagnesemia 513 Hypermethioninemias 220 Hypernatremia 412 Hyperornithinemia 206, 428 Hyperosmolar nonketotic coma 328 Hyperparathyroidism 507, 508, 511, 512 Hyperphenylalaninemias 428 Hyperprolinemia 431 Hypertension 336, 339, 411, 536 Hypertonic contraction 411 expansion 411 fluids 413 hyponatremia 413 Hypertyrosinemia 239, 431, 428 Hyperuricemia 128, 566 Hyperventilation 395, 404 Hypervitaminosis 469 D 473 E 474 K 476 Hypoalbuminemia 382, 401, 535 Hypo-alpha-lipoproteinemia 342 Hypocalcemia 508, 512 Hypochloremia 417 Hypochloremic alkalosis 402 Hypochromic microcytic anemia 294 Hypogammaglobulinemia 691 Hypoglycemia 139, 140, 313, 330, 535 fatal 331f Hypoglycemic hormone 311 Hypokalemia 397, 402, 414, 535 Hypolipidemic drugs 340 Hypolipoproteinemias 341 Hypomagnesemia 415, 513, 535 Hyponatremia 412 Hypoparathyroidism 508, 511, 512 Hypophosphatemic rickets 472, 512 Hypopigmentation 236 Hypopituitarism 675 Hypoproteinemia 382 Hypothalamic and pituitary hormones 659 neuropeptides 659 Hypothalamus 537 Hypothyroidism 336, 344, 676 777 Hypotonic contraction 411 expansion 411 fluids 413 hyponatremia 413 Hypouricemia 568 Hypoventilation 403 Hypovolemia 410 Hypoxanthine 560 Hypoxia 292 I Identification of virus infection 621 Imidazole aminoaciduria 244 Imino acid 24, 26, 198 glycinuria 199 Immobilized enzymes 309 Immunoelectrophoresis 448, 448f Immunofluorescence 454, 454f Immunoglobulin 689 molecule 687f Immunological tests in liver disease 355 renal diseases 374 Immunology of AIDS 702 Immunoselection of virus 703 Impaired fasting glycemia 315, 324 glucose regulation 315 tolerance 315, 324 Importance of carbohydrates 530 creatinine clearance 367 glucuronic acid pathway 134 proteins 532 pyruvate dehydrogenase 116 urea clearance 369 In situ hybridization 635 In vitro synthesized-protein assay 642 Indole ring 240 Infantile beriberi 478 Refsum’s disease 155 scurvy 497 778 Textbook of Biochemistry Infarction 335 Infliximab 696 Infusion of fluids 411 Ingram’s technique 40 Inheritance of HBS-C disease 293f pattern of hemophilia 388f Inherited disorders 155 Inhibition of cell division 730 Inhibitors of ATP synthesis 265 DNA replication 586 oxidative phosphorylation 265 protein synthesis 605 in mammals 605 RNA synthesis 593, 593t TCA cycle 254 Inhibits gluconeogenesis 313 plasminogen activation 179f Initial number of cells 737 Initiation of protein synthesis 600 transcription 590 Inorganic acidosis 401 ions 59 mercury 552 pyrophosphate 258 Inositol triphosphate 495, 655f Insulin 113, 165, 318, 323 biosynthesis 318f deficiency 323, 416 dependent diabetes mellitus 323 injections 330 like growth factor receptor 742 resistance syndrome 325, 333 signaling pathway 656 therapy 512 Insulinoma 331 Integral membrane proteins 16 Integration of major metabolic pathways 251 Interconversion of amino acids 201 one-carbon groups 207 vitamin A molecules 464f Intermediate density lipoprotein 173, 176 filaments 726 Internal hemorrhage 498 Interorgan transport of amino acids 200, 200f Interpretation of blood urea value 370 creatinine clearance 368 gastric juice analysis 357 glycohemoglobin values 329 urea clearance value 370 Interrelations of amino sugars 142f Interstitial fluid 408 implantation for treating cancer 735 Intestinal digestion of proteins 198 malabsorption 508 system 228 villous cells 470 Intracellular fluid 408, 409 protein degradation 199 Intrahepatic cholestasis 305, 349, 351 Intralysosomal accumulation 145 Intravenous GTT 316 Inulin 79 clearance 371 Iodine 521, 735 metabolism 672 number 88 Ion channels 18 exchange chromatography 451, 451f Ionic bond 5, 5f in protein interactions 5f forms of amino acids 27f Ionization of aspartic acid 28f Ionized calcium 505 Ionophores 19 Iron absorption 517 containing proteins 514t deficiency 518 anemia 518, 519f produces free radicals 435f sulfur complexes 514 toxicity 520 vessels 520 Ischemia modified albumin 305 Ischemic heart disease 342 Isocitrate dehydrogenase 248, 253, 257 Isoelectric focusing 448 precipitation 41 Isoenzymes of alkaline phosphatase 306 CK 302 Isohydric transport of carbon dioxide 287 Isoleucine 26, 27, 223, 230, 450, 451 Isomaltose 77, 78f Isoniazid 482 Isonicotinic acid hydrazide 60 Isopentenyl pyrophosphate 171f Isosthenuria 373 Isotonic contraction 410 expansion 411 fluids 413 Isotope dilution technique 735 Isovaleric aciduria 208, 230, 430 J Jaffe’s test 367 Jaundice 278, 346f, 348 Jejunal mucosa 149 K Kartagener’s syndrome 724 Karyorrhexis 163 Kaschinbeck disease 523 Keratan sulfate 80, 143, 145 Keratomalacia 467, 468f Keshan disease 523 Ketogenesis 141, 163, 165, 322, 323, 326 Ketogenic amino acids 245, 252 Ketone bodies 100, 101, 103, 364, 365 Ketonemia 165, 326 Index Ketonuria 165, 326 Ketosis 165, 166, 326, 327, 400 Kidney 470 distal tubular cells 470 function tests 329, 361 scanning 736 Kill bacteria 185 Kimmelsteil-Wilson syndrome 316, 328 Kinase phosphorylates enzymes 652 Kjeldahl’s procedure 44 Klenow enzyme 643 fragment 580 Klinefelter syndrome 324 Klotho protein 505 Kornberg’s enzyme 580 Koshland’s induced fit theory 54f Krabbe’s disease 428 leukodystrophy 193 Krebs citric acid cycle 251f cycle 247, 249f, 254 Kussmaul’s respiration 166, 402 Kwashiorkor 535 L Lactalbumin 420 Lactate 77 dehydrogenase 67, 111, 303 production 100 Lactic acid cycle 114 acidemias 429 acidosis 117, 128, 140, 328, 400, 404, 428, 430, 478 Lactose 77, 77f free diet 140 intolerance 144, 430 synthesis 138, 420 Lactosuria 317 Lactosyl ceramidoses 193 Lambert’s law 455 L-amino acid oxidase 202f Large offspring syndrome 623 L-asparaginase 717 Late protein synthesis 621f Latent jaundice 278 Lathyrus sativus 555 Lead poisoning 276, 518, 519, 551 Leber’s hereditary 631 neuropathy 606 optic neuropathy 268 optic neuropathy 611 Lecithin 90 cholesterol acyl transferase 180f lysolecithin acyl transferase 192 Left ventricular hypertrophy 336 Leigh’s syndrome 606 Lens of eye 133 proteins 727 Lepore hemoglobin 611 Leprosy 375, 508 Lesch-Nyhan syndrome 430, 568 Lethal infantile mitochondrial ophthalmoplegia 268 mutations 614 Leuconostoc mesenteroides 66 Leucine 26, 27, 223, 230, 450, 451 aminopeptidase 198 Leukemia 641, 469 Leukocyte adhesion deficiency 144 alkaline phosphatase 306 esterase 364 migration 726 Leukoderma 234 Leukopenia 490 Leukotriene 188, 190, 191f Levels of organizations of proteins 37f Levy Jening’s chart 444 Liddle’s disease 20 Ligand binding domain 657 Limiting amino acid 534 Limits of compensation 405, 405t Lineweaver-Burk equation 58 plot 57, 57f 779 Linkage analysis 628 of heme with globin 284f Linoleic acid 186, 187, 187f Lipid accumulating 193, 347 peroxidation 186, 437 storage diseases 92, 193t, 194, 194f Lipogenesis 321 Lipolysis 165, 323 Lipolytic enzymes in intestines 148 Lipoprotein 173 cascade pathway 176 glomerulopathy 175 lipase 161, 176 metabolism 180f, 335f Liposomes 90 Lipoxin 190, 191f Lithium 524 Liver 101 adipose tissue axis 162 and gastric function tests 346 cells 307 cirrhosis 384 diseases 305, 353 function tests 346, 348, 349, 355t glycogen 123 metastases 354 mitochondria 163 regeneration 355 Lobry de Bruyn-van Ekenstein transformation 73f Location in human chromosome 710 of gout attack 567f Lohmann’s reaction 211, 212f, 222 Long chain fatty acids 184, 185 saturated fatty acids 339, 341 QT syndrome 20, 415 Lovastatin 61 Low blood sugar causes glucagon secretion 322f carbohydrate ketogenic diet 330 density lipoproteins 173, 177, 436 780 Textbook of Biochemistry HDL cholesterol 336 phenylalanine 237 Lower blood glucose 313 surface tension 147 Lowering of activation energy 51, 51f Lowry’s method 44 L-phosphatidic acid 89f Luminiscence 455 Lundh test 359 Lung maturity 423 surfactants 91 Lymph node enlargement in porta hepatis 349 Lymphoma 281, 375 Lynch syndrome 585 Lynen’s spiral 156 Lysine 26, 27, 29, 216, 223, 226, 451 vasopressin 659 Lysinuric protein intolerance 199 Lysolecithin 90 Lysosome 11, 12, 14, 199 M Macroamylasemia 358 Macrocytic anemia 490 Macrophage 687 colony stimulating factor 696 inflammatory proteins 696 migration inhibition factor 696 Maillard reaction 328 Main functions of kidney tubules 362t Maintaining blood sugar 311 Maintenance of nitrogen balance 533 Major catabolic pathway of tryptophan 240 Malabsorption 359, 512 Malaria 307 Malate aspartate shuttle 117, 118, 118f, 226, 260 dehydrogenase 118f, 248, 257 shuttle 260 Malic enzyme 159 Malignant hypertension 370 hyperthermia 121, 726 melanoma 234 transformation 711 Maltose 77, 77f Mammalian DNA polymerases 580 RNA polymerases 589 system 590 Mammary glands 132 Management of diabetes mellitus 330 hypercalcemia 508 ketoacidosis 166 ketosis 327 metabolic syndrome 325 sickle cell disease 292 Mancini’s technique 45 Manifestations of deficiency 475 liver dysfunction 348 mutations 614 Maple syrup urine disease 208, 230, 431 Marasmus 535 Marfan syndrome 222 Markers of bone diseases 510 formation 511 resorption 510 glomerular filtration rate 366 permeability 371 hepatic dysfunction 349 myocardial infarction 302t obstructive liver disease 353 Mass spectrometry 458, 458f Massive blood transfusions 512 Master lipid regulator in liver 160 Maternal serum alpha fetoprotein 425 Matrix assisted laser desorption ionization 458 metalloproteinases 742 McArdle’s disease 144 Measurement of alpha fetoprotein 423 bilirubin 349 glomerular filtration rate 366 osmolality 373 pancreatic enzymes 358 Mechanism of absorption of calcium 503 action of hormones and signaling molecules 649 insulin 319 nitric oxide 228 PTH 506 steroid hormones 667 thyroid hormone 674 HCl secretion 356 insulin secretion 319f regulation of pH 393 Medium chain fatty acids 184 Medullary carcinoma of thyroid 508 thyroid carcinoma 716 Megadose of vitamin C 499 Megaloblastic anemia 494 Meister cycle 199f Melanin synthesis pathway 234f Melanocyte stimulating hormone 234 Melatonin 239, 241, 242 Melting of DNA 576 Membranes of organelle 16 Memory aid for essential amino acids 27 Menke’s disease 355, 521 kinky hair syndrome 521 Mental retardation 139, 143, 145, 221, 244, 245 Mercury poisoning 552 Meselson-Stahl experiment 579f Messenger RNA 587, 588 Metabolic acidosis 166, 398, 399, 402, 416 alkalosis 398, 402, 403, 403t, 405 alterations in brain 100f cancer cells 712 Index derangements in diabetes mellitus 327f fate 228 of amino acids 245f of pyruvate 115 functions of cysteine 217 serine 214 junction point 117f pathways of carbohydrates 137 profile of organs 99 syndrome 324, 325, 333, 536 traffic circle 252 Metabolism of adipose tissue 161 alcohol 140 amino acids 197f, 200 sugars 142 arginine and ornithine 227f ascorbic acid 496 aspartic acid 225f catecholamines 235f chylomicrons 176f histamine 243f histidine 243f ketone bodies 163 sulfur 219 thyroid hormones 673f tryptophan 239f vitamin E 473 Metachromatic leukodystrophy 193 Metallo-enzymes 50 Metallopeptidase inhibitor 745 Metastatic breast cancer 641 carcinoma of bone 508 and hyperparathyroidism 354 Met-hemoglobin 218, 289 reductase system 289f Met-hemoglobinemias 134, 289 Methionine 24, 26, 27, 210, 216, 450, 451 adenosyl transferase 216, 229f Methotrexate 60, 61, 571, 620, 716 Methyl cobalamin 492 Folate trap 493 malonic acid 494 aciduria 155, 431, 493 malonyl CoA isomerase 493 mercury 552 transfer 216 reactions 217 transferase 489f Methylenetetrahydrofolate reductase 498 Methylmalonic aciduria 208, 429 Metyrapone test 667 Micellar formation 89 Michaelis constant 57 Menten theory 53, 67 Microalbuminuria 372 Microarray technique 635 Microcytic hypochromic anemia 519 normochromic anemia 521 Microsomal cytochrome 12, 258 ethanol oxidizing system 140 heme oxygenase system 277 system 186 Microsome 11, 155 Microtubules 726 Microvilli 16 Miester cycle 198 Migraine 236 Milk alkali syndrome 404, 512 Millon’s test 31 Minamata disease 552 Mineral content of milk 421t Mineralization of bone 509 Minor pathways of deamination 202 purine bases 560 Mitochondria 11, 13, 13f, 14, 248 Mitochondrial cytochrome 258 DNA and RNA 605 encephalopathy lactic acidosis 606 membrane permeabilization 268 permeability transition pore 268, 616 781 system 268 transport systems 267 Mitogen activated protein kinase 743 Mitomycin C 717 Mixed micelle formation 149 triglycerides 87 Mode of action of enzymes 51 Modifications of amino acids 603 Molecular structure of antigens 693 Molecule of polyunsaturated fatty acid 180 Molybdenum 51, 523, 565 Mono sodium glutamate 556 Monoamine oxidase 236, 241 Monoamino dicarboxylic acids 24 monocarboxylic acids 24 Monoclonal antibody 717 band 690 Mono-oxygenase 232, 258 Monosaccharides 69 Monounsaturated fatty acids 86, 185, 532 Movement of sperms 726 Mucopolysaccharidoses 80, 82, 145 Mucoproteins 81 Mucosal block theory 515 Multidrug resistance protein 278 Multienzyme complex 66, 210, 248, 570 Multifactorial disorders 611 Multiple endocrine neoplasia 245, 357, 711 myeloma 375, 382, 401, 508, 690, 715 sclerosis 16, 194, 422 Multispecific organic anion transporter 278 Multistep progression 707 Muscle 504 cramps 508 diseases 308 lacks glucose-6-phosphatase 125 proteins 724 weakness 511 782 Textbook of Biochemistry Muscular dystrophies 212, 303, 324 Mutagens 614, 705 Mutation detection techniques 641 Mutual supplementation 534 of cereals and pulses 539 of proteins 534 Myasthenia gravis 495 Mycobacterium tuberculosis 629 Myelin sheath 16, 495 Myeloperoxidase 133f, 304, 434 Myocardial infarction 169, 179, 202, 212, 302-305, 308, 335, 354, 436, 483 Myoclonic epilepsy 268, 606 Myoglobin 294, 304 chain 294f in urine and blood 295 Myoglobinuria 295 Myosin 724 kinase 504 Myotonic dystrophy 324 N N-acetyl glucosamine 82 glutamate 205 muramic acid 82 neuraminic acid 194f, 712 Naphthoquinone 474 Natural amino acids 29 course of disease 700 Needle shaped crystals 74 Negative acute phase proteins 385 Neonatal hypoglycemia 138 mortality 315 tyrosinemia 239 Neostigmine 61 Nephelometry 45 Nephron loss proteinuria 372 Nephrosis 370, 518, 519 Nephrotic syndrome 336, 344, 372, 412, 508 Nerve cell 632f conduction 504 Neural tube defects 352 Neurotoxins 551 Neutral amino acids 198 fats 87, 531 sulfur 514 Nezelof’s syndrome 692 Niacin 477, 480, 486 deficiency 240, 241, 481, 481f, 482 Nickel ions 306 Nicotinamide 50, 216 adenine dinucleotide phosphate 480 deficiency 240 Nicotinic acid 240, 340 pathway of tryptophan 240 Niemann-Pick disease 192, 193, 428, 430 Night blindness 467 Ninhydrin test 430 Nitric acid 279 oxide 223, 224, 227, 290, 434 synthase 227, 270, 434 Nitrogen balance 533 Nitrogenous substances 218 N-methyl D-aspartate 228 transferase 235 Nocturia 373 Node of Ranvier 16 Nomenclature of carbon atoms 87 Non-alcoholic fatty liver disease 163 steatohepatitis 163, 305, 325, 351, 353, 354 Non-carbohydrate reducing compounds 317 Non-competitive inhibition 61f Non-esterified fatty acids 181, 538 Non-HDL cholesterol 338 Non-Hodgkin’s lymphoma 641 Non-insulin dependent diabetes mellitus 324, 333 Non-isotopic immunoassays 453 Non-ketotic hyperglycinemia 208, 213, 245 Non-oxidative deaminations 202 Non-phosphorylated lipids 92 Non-protein nitrogen 365 Non-steroidal anti-inflammatory drugs 189, 195 Norepinephrine 216, 235 Normal anion gap 404 metabolic acidosis 400, 401 composition of amniotic fluid 422t constituents of cells 709 hydrochloric acid secretion 357t iron kinetics 515f oxygen atom 433f pH 393 RBCs 291f serum electrolyte 404, 405 level of magnesium 512 Normoglycemia 313 Normotonic hyponatremia 413 Nuclear receptors 657 Nucleated RBC 294f Nucleic acid 559, 560 of virus 708 research 735 testing 701 Nucleoside 560-562 diphosphate 562 monophosphate 562 triphosphate 562, 562t Nucleotide 561 excision repair 583, 584, 584f phosphatase 305, 306, 308, 354 Number of hydrogen atoms 279 Numbering of amino acids in proteins 35 Nutritional deficiency of iron 518 importance of lipids 531 Nyctalopia 467 Nystagmus 238 O Oasthouse syndrome 199, 220 Obermeyer test 242 Obesity 163, 336, 339, 536 index 536 Index Obstruction of bile duct 150 urinary tract 416 Obstructive jaundice 280, 281, 336, 350, 354 liver disease 354 stage of viral hepatitis 281 Oculocerebrorenal syndrome 729 Oculocutaneous tyrosinemia 239 Okazaki fragments 581 Oligomycin 264, 265 Oligosaccharides 69 Omega fatty acids 163, 339 oxidation 155 Oncogenes 709, 710 Oncogenic viruses 351, 707, 713f Optic neuritis 553 neuropathy 631 Oral cavity 498 contraceptives 412, 484 glucose tolerance test 314, 315f, 333 rehydration fluid 106 Organ perfusion 97 slices 97 Organic acid 208 disorders 208 acidosis 400 acidurias 154, 400, 428 mercury 552 Organization of electron transport chain 260 proteins 34 Organophosphorus 553 compounds 553 insecticides 307 Ornithine 31, 227, 450 decarboxylase 62, 229f transcarbamoylase 204, 209 Orotic aciduria 430, 570 Osazone formation 74 Oseltamiver 61, 621 Osmolal gap 401 Osmolality of extracellular fluid 408 plasma 408, 408t Osmotic diuresis 166, 373 Osteitis deformans 354 Osteoblastoma 354 Osteoblasts 305, 505 Osteocalcin 475, 509, 511, 743 Osteoclasts 506 Osteoid 498, 509 Osteomalacia 354, 471, 472, 510 Osteonectin 743 Osteopetrosis 510 Osteopontin 743 Osteoporosis 510 Osteoprotegerin 743 Ovarian cancers 714 hormones 669 Oxalic acid 515 Oxaloacetate 248 junction point 249 Oxidation 285 of acetyl CoA 165 of fat carbohydrate 252f of fatty acids 87 of homogentisic acid 237f of iodine 672 of odd chain fatty acids 154 of sugars 74 products of glucose 74f Oxidative deamination of glutamate 202 decarboxylation 248 phosphorylation 111, 256, 263 Oxidized fatty acids 336 Oxoprolinuria 199 Oxygen dissociation curve 284, 285 P Paget’s disease 508, 510 Palmitic acid 15, 85, 153, 156 Pancreatic digestion of proteins 197 elastase 358 enzymes 358 function tests 358, 359t lipase 148 Pancreozymin 197 Pantothenic acid 477, 484, 486 Paper chromatography 449, 449f Para amino benzoic acid 477, 488 Paracetamol 189 Paradoxic acidosis 402 Paralysis of respiratory 404 Paraproteinemia 401, 690 Parathyroid function tests 508 hormone 505, 509 Paraventricular nucleus 660 Parenchymal diseases 353 Parent cell 579f Paresthesia 508 Parkinson’s disease 245, 552, 606 Paroxysmal nocturnal hemoglobinuria 16, 144 Partial gastrectomy 357 hydrolysis 40 reversal of glycolysis 118 Pathogenesis of ascites 347f Prion diseases 728 Pathology of maple syrup urine disease 231f Pathways of glucose 105, 123 Pauly’s test 32 Pellagra 242, 481, 483 Penicillin 61 Pentagastrin stimulation test 357 Pentose phosphate 130 pathway 129, 159 sugar 559 Pentosuria 317 Penultimate carbon atom 70f Pepsin 197, 308, 357 Peptide bond formation 31, 31f, 34f, 601 partial double bond 34f Peptidyl transferase 592, 601, 602 783 784 Textbook of Biochemistry Peripheral blood picture 490 smear 519 neuritis 483 neuropathy 495 proteins 15 smear 494 Pernicious anemia 357 Peroxidase 13, 258, 435f Peroxidation of polyunsaturated fatty acids 438f Peroxisomal biogenesis disorders 185 defects 430 deficiency diseases 13 oxidation 185 Peroxisomes 13 Peroxy nitrite 228, 434 Pertussis toxin 653 Phagocytosis 22, 497 Phagosomes 22 Phenylalanine 26, 27, 29, 31, 232, 233, 245, 450, 451 catabolism 232f hydroxylase 232, 232f, 236, 258 load test 237 Phenylketonuria 236, 246, 431 carrier state 237 Philadelphia chromosome 708 Phosphate 19f, 142 buffer system 394 infusion 508 mechanism in tubules 396f Phosphatidates 89 Phosphatidic acid 89 Phosphatidyl ethanolamine 191f inositol 495 bisphosphate 655f serine 191f Phosphatidylcholine 90 Phosphatidylethanolamine 91, 91f Phosphatidylglycerol 91 Phosphatidylinositol 91, 91f Phosphodiester bonds 574 Phosphoenolpyruvate 258 carboxykinase 118, 118f, 320 Phosphofructokinase 63, 109, 113, 121, 320 Phosphoglucomutase 124, 124f Phosphogluconate oxidative pathway 129 Phosphoglyceromutase 111 Phospholipase 90, 189 Phospholipid 89, 495 synthesis 495 Phosphoproteins 214 Phosphoribosyl pyrophosphate 240f, 563, 563f Phosphoric acid 89, 92, 561 Phosphorus 507, 511, 551, 735 Phosphorylase enzyme 483 kinase 127, 504 Phosphorylation 603, 652 Phosphosphingosides 91, 92 Photoelectric colorimeter 455, 455f Photophobia 238 Phytanic acid 155 Phytic acid 515 Pineal gland 242 Pinocytosis 21 Pituitary adenoma 668 Plasma ACTH 667, 668 ammonium 428 bicarbonate 405 bile acids 355 bilirubin 278 cells 686 cortisol 668 lactate 428 lipids 173 membrane 14 osmolality 373 proteins 378 TSH 675, 676 Plasmacytoma 690 Plasmalogens 91, 192 Plasmid liposome complex 631 Plasminogen 179 Plasmodium falciparum 145 infection 134 Platelet aggregation 190 Plummer-Wilson syndrome 519 Pneumocystis carinii 704 Pneumonia 404 Polarity of DNA molecule 575 Polyacrylamide gel electrophoresis 447, 447f Polyamine synthesis 229f Polycystic ovarian syndrome 680 Polycythemia vera 737 Polydypsia 326 Polymerase chain reaction 638, 638f, 645 Polyneuritis 478 Polynucleotide 575f Polyol pathway of glucose 135, 135f Polypeptide 693 Polyphagia 326 Polyphenols 435 Polyribosomes 602, 603f Polysaccharides 70, 78 Polyunsaturated fatty acids 13, 85, 86f, 180, 186, 339, 437, 531, 532 Polyuria 326 Pompe disease 129, 144, 428, 429 Porphobilinogen synthase deficiency 275 Porphyria 274 cutanea tarda 275f Porphyrin ring 271f Portal hypertension 348 lymphadenopathy 351 vein thrombosis 348 Porter-Silber reaction 666 Positron emission tomography scan 736 Post-hepatic jaundice 350 Post-prandial blood sugar 313 hypoglycemia 331 Index Poststreptococcal glomerulonephritis 375 Post-translational processing of collagen 722 Potassium 363, 413 chromate 550 excretion 414 ion 19f Powerhouse of cell 13 Prader-Willi syndrome 324 Pre-eclampsia of pregnancy 221 Pre-hepatic jaundice 350 Preparation of specific human gene 626 Preventable blindness 468 Prevention of atherosclerosis 339 met-hemoglobinemia 133 Primary biliary cirrhosis 351 deficit of carbonic acid 403 excess of bicarbonate 402 carbonic acid 403 familial hypercholesterolemia 342 hemosiderosis 520 hepatoma 281 hyperoxaluria 213 hyperthyroidism 676 hypothyroidism 676 structure of human insulin 35f insulin 35 Principles of anti-sense therapy 593f heredity 608 radioimmunoassay 452, 452f thermodynamics Processing of rRNA 598 tRNA 597 Production of bilirubin diglucuronide 278f genomic library 630f homogentisic acid 233 hybridoma 640 niacin 483 Progression of atherosclerosis 335 Prokaryotes 570 Prokaryotic cell Prolactin stimulation test 663 Proline amino peptidase 198 Prolonged in liver disease 355 Promoters of cancer 706 Promotes glycogenolysis 313 glycolysis 313 Properties of amino acids 27 fatty acids 86 Propionic aciduria 208, 429 Propionyl CoA carboxylase deficiency 155 Prostacyclin 188, 190, 190t Prostaglandins 188 Prostate cancer 306, 308 Protease inhibitors 52, 554 Protein 422, 534 biosynthesis 596 bound calcium 381, 505 buffer system 394 calorie malnutrition 163 catabolism 674 deficiency 533 energy malnutrition 534 kinase 653, 653t, 655f misfolding diseases 729 phosphatase 127 phosphorylation 64 selectivity index 372 targeting 603 truncation test 642 Proteinuria 371 Proteoglycan 81, 142, 143 Proteolytic digestion of myosin 725f Prothrombin 385, 475, 476 time 352, 385 Proton motive force 264 pump 263 Proto-oncogenes are regulatory genes 709 785 Protoporphyria 351 Proximal convoluted tubule 361, 362, 395 histidine 283 Pseudocholinesterase 307 Pseudohyperkalemia 413, 415, 416 Pseudohypoparathyroidism 508, 509 Pseudouridine arm of tRNA 597 Pteroic acid 488 Pulmonary hypertension 228 Pulsed field gel electrophoresis 448 Purine nucleoside phosphorylase 566f synthesis 563t, 564f Puromycin 605 Purulent meningitis 422 Putrefaction of tryptophan 242 Pyranose ring 72f Pyridoxal phosphate 50, 124, 201, 215, 224, 271, 482 Pyridoxamine 482 Pyridoxine 477, 482, 486 Pyrimethamine 61, 491 Pyrimidine 477 ring 226 synthesis 571 Pyrrole ring 271f Pyrrolidine 26 Pyrrolysine 31 Pyruvate carboxylase 63, 120, 428, 486, 504 deficiency 121 reaction 117 dehydrogenase 115, 117, 247, 257, 320, 477, 504 complex 115 kinase 111, 113, 117, 256, 320, 504 transporter 115 Q Quantitation of proteinuria 372 Quantitative PCR 639 preparation of biomolecules 624 real-time PCR 639 786 Textbook of Biochemistry Quarter staggered arrangement 721 Quinolinate phosphoribosyl transferase 240, 240f R Radial immunodiffusion 45, 45f Radiation protection 738 Radioactive iodine 453, 675 Radioimmunoassay 452, 735 Radium needles 737 Rancidity of fat 88 Random blood sugar 313 Rapaport Leubering cycle 115 Raynaud’s disease 375 Reabsorption of bicarbonate 395 calcium 506 solutes in tubules 362 water 363 Reaction in liver 465f lungs 288f amide group 30 amino acids 29 CoA derivatives 485f cycle preparatory steps 247 glycogen phosphorylase 124f lactate dehydrogenase 50f monosaccharides 73 oxaloacetate 250f Receptor mediated endocytosis 21 Reciprocal regulation of glycogenolysis 126f Recommended daily allowance of thiamine 479 Red depicts blood 465f Reduce dietary cholesterol 339 Reduced DNA synthesis 490 excretion rate 567 Reflectance spectrophotometry 457 Refsum’s disease 155 Regeneration of glucose-6-phosphate 131 oxaloacetate 248 Regulation of acid secretion 357 ATP synthesis 265 beta oxidation 154 blood glucose 311 sugar 313f calcitriol formation 471 cholesterol synthesis 172f citric acid cycle 253 color of skin 234 deoxyribonucleotide formation 569t fatty acid synthesis 159 gene expression 616 gluconeogenesis 120 glycogen metabolism 126 glycolysis 112 glycosis 113f heme synthesis 273 HMG CoA reductase 172f HMP shunt pathway 131 ovarian hormones 669 purine synthesis 565 pyrimidine synthesis 570 secretion of HCl 356f sodium and water balance 409 synthesis 189 urea cycle 204 Relative capacity of buffer systems 394 Renal acid excretion 397 artery stenosis 415 blood flow 362 disease 370, 512 failure 400, 404, 508, 511 function tests 361 glucosuria 316, 317 impairment 417, 512 insufficiency 220 osteodystrophy 510 plasma flow 371 regulation of pH 395 rickets 472 tubular acidosis 401, 404, 412, 415, 417, 508, 511, 512 Renin angiotensin aldosterone 410f system 409 Reperfusion injury 436, 436f Replication bubble 580, 581f of DNA 578 of HIV 701 Requirement of biotin 486 iron 514 pantothenic acid 485 vitamin B12 494 C 498 D 473 zinc 522 Residual renal function 371 Respiratory acidosis 398, 403, 405 alkalosis 398, 403, 405, 512 burst 22, 434 chain 255, 479 diseases 436 distress syndrome 91, 436 tract 190 Restriction endonucleases 309, 586, 625 fragment length polymorphism 637 map 625 sites 625 Retention jaundice 350 Reticulocytosis 490 Retina 20 Retinal degeneration 244 isomerase 466 Retinitis pigmentosa 185 Retinoblastoma oncosuppressor protein 615 protein 744 Retinoic acid receptors 467 Retinol binding protein 372, 464 palmitate 464 Retrolental fibroplasia 436 Index Retroviruses 629, 630 Reverse transcriptase PCR 639 Reversible oxidation-reduction 496 Rheumatoid arthritis 144, 375, 436, 641 Rhodopsin 465 RIA and ELISA tests 45 Ribavirin 621 Riboflavin 477, 479, 486 deficiency 479 structure 479f Ribonucleic acid 559, 587 Ribonucleoside 561 phosphates 562 Ribonucleotide 561 reductase 571f complex 571 Ribosomal RNA 587, 598 Ribozymes 65, 592 Rickets 471, 354, 510 Right handed double helix 575 Rituximab 717, 718 RNA synthesis 621f viruses 629 Role of amylase 309 antioxidants 438 carnitine 151 cyclic GMP 655 liver in fat metabolism 162 Romberg’s sign 494 Rosenheim reaction 32 Rothera’s test 166, 326, 365, 429 Rotor syndrome 280 S S-adenosyl methionine 216, 217, 222, 229f, 235, 258, 548 Sakaguchi’s test 32 Salicylate 318, 400 Salivary alpha-amylase 105 Salvaging of iodine 674 Sandhoff’s disease 193 Saponification 88f Sarcoidosis 508 Sarcoplasmic reticulum 725 Saturated and transfatty acids 188 fatty acid 85, 86, 532 Schilling test 359, 494 Schlesinger’s reaction 279 test 279, 365 Schwann’s cells 16 Scleroderma 375 Scurvy 497 Second law of thermodynamics Secondary hyperthyroidism 676 hyperuricemia 567 hypothyroidism 676 immunodeficiency 692 structure of proteins 36 Secretin cholecystokinin test 358 Secretion of adrenal hormones 665 hormones 504 insulin 318 Segment of nephron 362 Selective serotonin reuptake inhibitors 240 Selenocysteine 31, 32, 214, 599 Self-monitoring of blood glucose 458 Seliwanoff’s test 317 Sensitive gel electrophoresis 642f Sephadex chromatography 451f Sequelae of protein calorie malnutrition 536 Sequence of amino acids in proteins 34 Serine 26, 29, 207, 210, 216, 450 metabolism 215f proteases 52 Serotonin 239, 240 and melatonin synthesis 241f Sertoli cells 670 Serum bilirubin 355 electrophoresis 352 ferroxidase 520 globulins 352 787 glutamate dehydrogenase 141 oxaloacetate transaminase 305 pyruvate transaminase 305 proteins 507 triglyceride 338 Severe hepatocellular disease 355 Sex hormone binding globulin 669 linked recessive inheritance 610, 610f steroids 509 Sheehan’s syndrome 676 Short chain fatty acids 195 hairpin RNA 594 Shunt bilirubin 274, 274f Sickle cell 291f anemia 636 disease 291 hemoglobin 291 trait 291, 292, 292f syndromes 291 Sickling test 292 Sideroblastic anemia 275 Signal molecule 653, 740 Significance of cholesterol 334 gluconeogenesis 118 glycolysis pathway 108 heat coagulation 42 HMP shunt pathway 131 isoelectric pH 41 lactate production 112 PUFA 86, 186 transamination 201 Sildenafil citrate 228, 656 Simple amino acids 25f Single nucleotide polymorphism 4, 637 strand conformation polymorphism 641 Site directed mutagenesis 614 Sjögren’s syndrome 12, 375 Skeletal muscle 100, 101, 107, 176 ollinger 788 Textbook of Biochemistry Skin diseases 436 Small and medium chain fatty acids 185 chain fatty acids 184 nuclear RNAs 592 RNA 588 Smell of acetone 166 Sodium channels 20 cyclamate 81 dodecyl sulfate 447 fluoride 442 hydroxide 550 ion 19f potassium pump 19f pump 20, 21, 23, 106, 411 restriction 412 Softening of cornea 467 Soluble matrix 259 Somatic mutation 584 recombination of DNA 693 Sorensen’s formal titration 29 Sources of biotin 486 C and N atoms of pyrimidine 569f calcium 502 carbohydrates 530t folic acid 490 iron 514 lead poison 551 pantothenic acid 485 PUFA 532t vitamin D 473 E 474 K 476 Southern blot technique 634, 634f Spectrophotometer 456, 456f Spermidine synthase 229f Spermine synthase 229f Sphingolipidoses 193, 194 Sphingolipids 91 Sphingomyelin 92, 92f, 192 Sphingosine 91, 91f Spiranolactone 363 Split gene 693 Spontaneous decarboxylation 164 mutations 610, 713f Stages of compensation 399t oxidation of foodstuffs 255 Standard deviation index 445 urea clearance 370 Staphylococcus aureus 692 Starch tolerance test 359 Starling hypothesis 381f Starvation 163, 165 ketosis 332 Stearic acid 85 Stem cells 631, 632f Stereoisomers 70, 70f Steroid hormone 169, 664, 669t enters nucleus 656f Stimulation test 667 Storage of iron 517 vitamin B12 492f Streptococcus thermophilus 66 Streptomycin 605 Structure of ADH and oxytocin 659f alpha helix 37f ATP 51f beta-pleated sheet 37f biotin 485, 485f cholesterol 170f chylomicrons 175f co-enzyme 484f collagen 720 DNA 574 folic acid 488f heme 270, 271f hemoglobin 283 HIV 701f immunoglobulins 687 insulin 318 lipoic acid 115f mitochondrion 259 niacin 480f pantothenic acid 484f primary bile acids 181f proteins 34 purines 560f riboflavin 479 starch 78 sucrose 76f T-cell receptor 694f thiamine 477 pyrophosphate 478f tRNA molecule 596 vitamin A 464f B12 491f Subacute combined degeneration 494 Subarachnoid hemorrhage 422 Subcellular movements 726 organelle 10, 11 Subclassification of metabolic alkalosis 402 Subluxation of lens 221 Substrate concentration 56, 56f level phosphorylation 110, 111, 248, 256 saturation curve 56f strain 52 Succinate dehydrogenase 248, 254, 257 Q-reductase 261 thiokinase 248, 256 Succinylcholine 307, 495 Sucrose 77, 530 Sugars of nucleic acids 76f Suicide inhibition 62, 568 Sulfate conjugation 547 Sulfonamide 60, 61, 491 Sulfur containing amino acids 24, 25f, 220t, 483 Sulfuric acid 550 Superoxide dismutase 13, 133f, 434, 435, 435f Index Surgical removal of gallbladder 360 Synthesis of catecholamines 234 ceramide 192, 192f cerebrosides 192, 193f cholecalciferol 469f CoA 484f collagen 721 compound lipids 191 deoxythymine nucleotides 571 ferritin and transferrin receptor 516 gangliosides 193, 193f glutathione 212 glycerophosphatides 191 glycosphingolipids 192 heme 212 leukotrienes 191f melanin 233 mineralocorticoids 665f nitric oxide 227 non-essential amino acids 30, 201 phosphatidylcholine 191, 191f phosphatidylinositol 191 pregnenolone 664f purines 212 pyrimidine nucleotides 570f secretory proteins 605f sex hormones 666f sphingolipids 192 sphingomyelin 192 steroid hormones 664 structural and functional proteins 196 sulfatides 193 thymidylic acid 208f thyroid hormones 236 triacylglycerols 160 triphosphates 569 Systemic lupus erythomatosus 375 T Tamoxifen 670 Tandem mass spectrometry 458, 458f Tangier disease 342 Tartaric acid 306 Tartrate resistant acid phosphatase 510 Tarui’s disease 144 Tata-binding protein 590 Tau protein 728, 729, 745 Tay-Sach’s disease 193, 194, 430 Tendinous xanthomata 342 Testicular hormones 670 Testosterone 669, 670 Tetracycline 412, 605 resistance gene 627 Tetrahydrobiopterine 227f, 232 Tetrahydrofolic acid 207f, 501, 572f Thalassemia 290, 293, 294f, 518 syndromes 294 Therapeutic potential of arginine 227 use of enzymes 308t niacin 482 vitamin A 469 vitamin C 499 Thermogenesis 162, 674 Thiamine 115, 230, 477, 486, 560 deficiency 134 pyrophosphate 50, 115, 130, 477 Thiazide 363 Thin layer chromatography 449, 450f Thioredoxin reductase 214, 571f Threonine 26, 27, 210, 450, 451 Thrombin 385 Thrombopoietin 745 Thrombosis 221, 335 Thromboxane 188, 190, 190t Thymine 477, 560 Thyroid cancer 716, 737 function tests 674 hormones 528, 672, 674 scanning 736 stimulating hormone 662 Thyrotoxicosis 508, 512 Thyroxine synthesis 673f Tissue of origin 303, 669 polypeptide antigen 715 Titration curve of glycine 28f Total iron binding capacity 516, 519, 524, 525 parenteral nutrition 541 Toxic exposure 354 hepatitis 349 Toxicity of folic acid 491 niacin 482 vitamin B6 484 C 499 Trait of disease 609 Transamination 30, 201, 483 of alanine 119f reaction 29f Transfatty acids 15, 86, 341, 532 Transfer RNA 588, 596 carrying serine 597f general structure 597f Transferrin receptor protein 525 Transformation of cells in tissue culture 712f Transforming growth factor 745 Transient glucosuria 317 Transketolase reaction 130 Transmembrane proteins 16 Transmethylation 30 reactions 489f Transmissible spongiform encephalopathies 728 Transport chain 255 of amino acids 219 of carbon dioxide 287 of cholesterol 335f of glucose 320 of thyroid hormones 674 proteins 39, 382 Transportation of ammonia 203 Trapping of ammonia 203 Treatment of adenocarcinoma of colon and breast 716 hemosiderosis 520 789 790 Textbook of Biochemistry hyocalcemia 509 hyperkalemia 416 hypokalemia 415 iron deficiency 519 lead poisoning 552 metabolic acidosis 402 obesity 536 protein-energy malnutrition 535 Triacylglycerol synthesis 160 Tricarboxylic acid cycle 249f Triglyceride 87f Tripeptidases 198 Triple stranded collagen fiber 721f stranded helix 721 Tropical splenomegaly syndrome 375 Trousseau’s sign 508, 509, 524 Tryptophan 26, 27, 29, 207, 232, 239, 450, 451 hydroxylase 240, 258 metabolism 497 pyrrolase 64, 240, 258, 270 Tubeless gastric analysis 357 Tuberculosis 326, 508, 700 Tuberculous meningitis 422 Tuberous xanthomata 342 Tubular dysfunction 374 maximum 362, 374 proteinuria 372 reabsorption of phosphate test 508 Tubules handle substances differently 366f Tumor cell destruction 686 index substances 713 marker 306, 308, 506, 713, 715 metastasis 722 necrosis factor 695 alpha 696 beta 696 receptor 746 of bile duct 349 of bladder 370 Turner syndrome 324 Types of acid-base disturbances 398t bilirubin 349 bond 547 calcium channels 503f jaundice 349 lactic acidosis 400 metabolic pathways 99 radiation 734 rickets 472 transport mechanisms 21t systems 21f tumor produced 708 Tyrosinase 234, 238 Tyrosine 26, 29, 232, 233, 450, 451 hydroxylase 234, 258 Tyrosinemia 239 U Unconjugated bilirubin 139, 280, 350 Uncouplers of oxidative phosphorylation 265 Uniport system 21, 106 Units of chondroitin sulfate 80f Unsaturated fatty acids 85 Upper part of jejunum 488 Urea clearance test 369 cycle 196, 203, 226 disorders 206t, 428 enzyme 571 Uremic syndrome 370 Uric acid 363, 565, 566, 567 Uridine diphosphate 142 Urinary acidification 373 bilirubin 349 buffer 396 calculi 468 excretion 366 of porphyrins 276t free cortisol 668 hydroxyproline excretion 510 osmolality 373 steroids 666, 667 urobilinogen 350 Urine appearance 364t bile salts 350 collection 442 excretion 366 of alkaptonuria 238f Urobilinogen 349, 350, 365 Urocanic aciduria 244 Urogenic proteinuria 372 Uronic acid 74 Use of radioisotope tracers 98 Utilization of glucose 210, 321 V Valinomycin 19, 23, 265 Van Den Bergh direct test 350 indirect test 350 reaction 349 test 279 Van Der Waals forces Vanillyl Mandelic acid 236, 246 Vascular cell adhesion molecule 746 diseases 328 endothelial growth factor 746 occlusion in sickle cell anemia 291f Ventromedial nucleus 660 Verner-Morrison syndrome 681 Very long chain fatty acids 184, 186 low density lipoproteins 173, 176 Vibrio cholerae 653 Vinyl phenols 553 Index Viral hepatitis 349, 351 infection 422 Virus 144, 620, 708 carrying gene 710 Visualization of chromatography 449 protein bands 447 Vitamin A 464, 465f, 507, 707, 758 deficiency 468 B12 217, 488, 491 B6 deficiency 240 C 317, 438, 495, 497, 509, 519, 707 deficiency 244 D 469, 505, 507 and absorption of calcium 471, 505 and bone 505 and innate immunity 472 and metabolic syndrome 473 and renal tubules 505 deficiency 471, 472, 512 resistant rickets 21 E 163, 438, 340, 473, 707 K 474, 474f cycle 475f deficiency 352 dependent carboxylase 475 reductase 475f Volatile acids 393 Voltage dependent anion channel 268 Vomiting 412 Von Gierke’s disease 128, 136, 144, 331, 365, 430, 567 W Wald’s visual cycle 465f Waldenstrom’s macroglobulinemia 375, 690 Warburg’s hypothesis 114, 712 Water soluble vitamins 463 Watson-Crick model of DNA structure 575 Weak and strong acids 391 Wernick’s disease 141 Westergard multirule chart 444 Western blot 700 analysis for proteins 634 Wet beriberi 478 Whipple’s disease 242 White adipose tissue 162 WHO classification of malnutrition 535t Williams-Beuren syndrome 723 Wilson’s disease 353, 355, 384, 430, 521 hepatolenticular degeneration 352 Wobbling phenomenon 599 Wolman’s disease 344 X Xanthaslasma 342 791 Xanthine 560 oxidase 434, 436 deficiency 569 Xanthomas 342 Xanthoproteic test 31 Xanthosine monophosphate 564 Xanthurenic acid 240 aciduria 483 Xeroderma pigmentosum 584, 585 Xerophthalmia 467 X-linked adrenoleukodystrophy 23 recessive 133 Xylitol dehydrogenase 135 Y Y-linked inheritance 610 Z Zanamavir 621 Zellweger syndrome 13, 156, 185, 186, 603 Zidovudine 621 Zimmerman reaction 666 Zinc 51, 522 chloride 550 deficiency manifestations 522 toxicity 522 Zollinger-Ellison syndrome 357, 681 ... carbonic acid which dissociates into CO2 and H2O CO2 is thus eliminated by the lungs HHb + O2 HbO2 + H+ – + HCO3 + H H2CO3 H2CO3 H2O + CO2 iv The activity of the carbonic anhydrase (also called... regulation of pH are: A Excretion of H+ (Fig 29 .2) B Reabsorption of bicarbonate (recovery of bicarbonate) (Fig 29 .3) C Excretion of titratable acid (net acid excretion) (Fig 29 .4) D Excretion of NH4+... (NaHCO3/H2CO3) It accounts for 65% of buffering capacity in plasma and 40% of buffering action in the whole body Box 29 .2: Mechanisms of regulation of pH First line of defense Second line of defense