Biochemistry Part 1 PDF Past Paper - October 6 University

October 6 University ‫ أكتوبر‬6 ‫جامعة‬ Biochemistry For Medical Students Part 1 Dr./ Ismail Hegazy Professor of Biochemistry  Introduction...

October 6 University ‫ أكتوبر‬6 ‫جامعة‬ Biochemistry For Medical Students Part 1 Dr./ Ismail Hegazy Professor of Biochemistry  Introduction The objective of these handouts is to provide the students of the first level with the basic knowledge and understanding of the principles of biochemistry and to integrate the biochemical studies with the other topics of the basic medical sciences. Biochemistry deals with what happen inside the cell in order to generate energy needed for the normal cellular biological function. The contents concentrate on the basic structure. Types and normal functions and the recommended daily needs of the major components of the human food. Prof. Ismail Hegazy Professor of Biochemistry II Vision Faculty of Applied Medical Sciences is a locally and regionally leading faculty, characterized by graduating specialists with high efficiency in various applied medical specialties and by high production of distinct applied researches. Mission Faculty of Applied Medical Sciences is an educational, research and community institute aiming to prepare graduates able to compete locally and regionally in the field of applied medical specialties, through an advanced educational strategy, distinct scientific research and clear role in community service and environmental development. The mission is carried out through efficiency human expertise's and modern information technology. ‫ تهذف إلى إعذاد خشيجين قبدسين على المنبفست محليب وإقليميب في‬، ‫مؤسست تعليميت وبحثيت ومجتمعيت‬ ‫ ورلك من خالل استشاتيجيت تعليم وتعلم متطىسة وبحث علمي‬، ‫مجبل التخصصبث الطبيت التطبيقيت‬ ‫ من خالل خبشاث بششيت‬، ‫ ورلك لتنفيز سسبلتهب‬، ‫متميز ودوس واضح في الخذمت المجتمعيت وتنميت البيئت‬.‫راث كفبءة وتكنىلىجيب المعلىمبث الحذيثت‬ III  Content 1- Water metabolism………………………………………………….. 1 2- Physio-chemical principles………………………………………… 4 3- Carbonhydrates…………………………………………………….. 21 4- Lipids of physiological importance………………………………... 38 5- Proteins…………………………………………………………….. 57 6- Immunoglobulins………………………………………………….. 78 IV  Unit (1) Water Metabolism Water H2O  Tasteless, clear, odoulress fluid.  Humans can servive for 4-6 weeks without food, but for only few days without water. Biological importance of water: 1- Water is the principle chemical constituents of the body. It represents about 65% of the body weight in an adult male (55% in female). 2- Water is the medium in which chemical reactions takes place inside the cells. 3- It is the universal solvent in the body. 4- It is the important in regulation and maintenance of constant body temperature. 5- It is the principle constituent of all body fluids “blood, lymph, tissue fluid”. 6- It is the transporting agent of the body. 7- Water is the main constituent of secretions as saliva, gastric juice, bile, intestinal juice, sweat. 8- Water is the main constituent of the excretory fluid “urine”. The reference daily intake of water:  The daily needs of water depends on the water losses. Water losses are affected by the amount of physical exercise, the environmental temperature and humidity and the condition of the subject. -1-  The recommended daily intake is about 2500 ml – 3000 ml/day) for male.  Normally the water input “intake should equal the water output losses” Input = output  Water output: Water losses or output occur through the following: a) Urine = 750-1500 ml/day b) Perspiration “sweating” + water vapor in expired air = 500-800 ml/day “insensible fluid losses as they can not be easily measured. c) Water in the faeces = 100-150 ml/day The sum of output 2500 ml/day  Water output is regulated by: a) ADH = Anti Diuretic Hormone = Vasopressin ADH is secreted by the hypothalamus and stored and released by the posterior pituitary gland. - If the body is deficient in water as in dehydration, the secretion of ADH increases to suppress “decrease” the volume of urine. - If the fluid “water: level in the body is increased, “Hydration”, the secretion of ADH is decreased and the urine volume increases. b) Aldosterone Hormone: The decreases in water in the body  Stimulates Rennin-angiotensin system in the kidney  Stimulates Secretion of Aldosterone hormone from the adrenal cortex which stimulate the absorption of Na+ water form renal Tubules. -2-  Water input=intake Water supply occur through the following : a) Ingestion of fluids “drinking" = 1200 ml/day b) Ingestion of goods = 1000 ml/day c) Metabolic water = 300 ml/day Total = 2500 ml/day - Ingestion of fluids “drinking” is regulated by thirst. Water insufficiency increase osmolarity of extra cellular fluid stimulate osmoreceptors in the brain increase thirst sensation. -3-  Unit (2) Physio-chemical Principles Expression of Concentration: A solution is formed of a substance dissolved n a liquid. The dissolved substance is called a solute. The liquid in which the solute is dissolved is called the solvent. Together (solute + solvent) they represent a solution. Concentration: Concentration of a solute in solution can be expressed in many ways including the percent solutions, molarity, molality and normality. (a) Percent solutions : It is equal to the amount of solute per 100 total units of solution. The expression of percent solution can be done in three ways, namely - Weight/weight (W/W) - Volume/volume (V/V) - Weight/volume (W/V). This is the most commonly used unit. Examples of percent solution: Glucose solution (%%) contains 5 grams of glucose dissolved in 100 ml of distilled water. Saline (NaCl solution 0.9%) contains 0.9 grams of NaCl salt in 100 ml distilled water. -4- (b) Molarity (M): Molarity is expressed as the number of moles per liter of solution. One more of a substance equals its gram molecular weight (the molecular weight expressed in grams). The system International d’Unites (SI) used mole/litre (mol/L) to express the concentration of a solution. Millimoles/liter (mmol/L), micromoles/Liter ( mol/L) and nauromoles/ Liter (nmol/L) are commonly used units. N.B. : One liter = 1000 milliliter (ml) One mole = 1000 millimole (mmol). One millimole = 1000 micromole ( mol) One micromole = 1000 nanomole (n mol) (c) Molality : Molality represents the amount of solute per one kilogram of the solvent. It is always expressed as moles per kilogram of the solvent. (d) Normality : Normality is defined as the number of gram equivalent weight per liter of solution. An equivalent weight of a substance is equal to the molecular weight of that substance divided by its valence. Normality is no longer used to express concentrations. N.B : - Dilute solution contains very little solute. - Concentrated solution contains large quantity of solute in solution. -5- - Saturated solution contains excess of undissolved solute particles. Law of Mass Action: This law describes the relation between the velocity of a chemical reaction and the product of concentration of the reacting substances. In a reversible reaction. Velocity (V1) A+B C+D Velocity (V2) V1 is proportional to [A] X [B] V2 is proportional to [C] X [D] V1 = K1 X [A] X [B] V2 = K2 X [C] X [D] At equilibrium V1 = V2 K1 X [A] X [B] = K2 X [C] X [D] K1 [C] X [D] ________ _________________ = = K (equilibrium contant) K2 [A] X [B] Applying this law for the dissociation of water, we get the following at equilibrium : V1 - H2O H+ - OH V2 - V1 [H+] X [OH ] ________ = ____________________ = K V2 [H2O] - K X [H2O] = [H+] X [OH ] -6-  As the concentration of H2O is nearly constant due to its weak ionization, its concentration can be considered a unit (1 mole/litre) -.. K X 1 = [H+] X [OH ] - The [H+] at equilibrium is very small and equals 10 -7 mol/L. Also [OH ] equals 10-7 mol/L The pH of water is defined as negative log its hydrogen ion concentration. pH = - log [H+] pH of water = - log 10-7 = - X – 7 =7 True and titrable acidity : An acid is defined as a proton (H+) donor and a base is a proton acceptor. True acidity is the amount of free hydrogen ion in solution. It determines the pH of the solution. True acidity is low in weak acids and high in strong acids. Combined acidity represent the non-ionized hydrogen in a substance in solution. The term Titrable acidity represent all the hydrogen in a solution whether free or combined. All these hydrogen ions can be used during neutralization (Titration) with a base. -7- pH and its Determination : The hydrogen ion concentration is often expressed as pH (pH represent the potential or the actual H) pH = - log [H+] or 1 ________ pH = log [H+] The hydrogen ion concentration is inversely proportional with the pH value. The pH of pure water is 7 “neutral” because the [H+] in water is 10-7. Any pH value below 7 is acidic and above 7 is alkaline Determination of pH : Methods for determination of pH include : 1. Colorimetric methods by using indicators. Indicators are weakly ionized acids or bases that change their colour with the change in the pH value. The degree of colour changes is matched with the colour of different standard buffers of known pH. Litmus paper change its colour according to the changes in the pH, thus Red litmus paper turns blue in alkaline pH, blue litmus paper turns red in acid pH. 2. Electrometric method by using the pH meter. This method depends on the difference in [H+] between an electrode and the solution whose pH is to be determined, thus creating a potential difference that can be measured. Determination of the pH of the blood is important in assessment of the acid-base balance and is essential in diagnosis of acidosis or alkalosis. -8- Buffers, Acidosis, Alkalosis: Definition: Buffers are solutions that keep the pH of a solution constant. Buffers resist any change in the pH after addition of acids or bases to the solution. Structure: Buffers are composed of weak acid and its salt or less commonly of weak base and its salt. Examples of buffers in the blood : (A) Extracelullar buffers: (1) Carbonic acid/bicarbonate buffer (H2CO3)/Na HCO3). It is the main buffers system in the blood. It is responsible for 60% of the buffering capacity of the blood. (2) Sodium acid phosphate/sodium alkaline phosphate (NaH2PO4/ Na2HPO4). (3) Plasma proteins (acid proteins/sodium proteinate). (B) Intracellular buffer “Red cell buffers” : 1. Hemoglobin buffer (acid Hb/K Hemglobinate). 2. Biocarbonate buffer (H2CO3/KHCO3). 3. Phosphate buffer (KH2PO4/K2HPO4). Mechanism of action of buffers: Buffers help to keep the pH of the blood constant inspite of continuous formation or addition of acids or bases to the blood during metabolism. -9- Examples of acids added to the blood : (a) Lactic acid arises from oxidation of carbohydrates in the muscles during muscular contraction and from the red blood cells (RBCs). (b) Phosphoric acid is formed during metabolism of phospholipids, phosphoroteins and nucleoproteins. (c) Sulphates from the sulphur containing amino acids. (d) Keto acids as aceto acetic acid and -hydroxybuteric acid which increase in untreated diabetes mellitus. Examples of alkalies that enter the blood include citrates, oxalates, bicarbonates. The main sources of these alkalies are the vegetables, the fruits and the milk. - Buffers acting in the plasma react directly with the added acids or alkalies as in the following examples : (a) If a strong acid as HCl is added, it will react with sodium bicarbonate. HCl + NaHCO3 NaCl (neutral) + H2CO3 (weak acid) (b) If a strong alkali as NaOH is added, it will react with H2CO3 as follows : H2CO3 + NaOH NaHCO3 (weak base) + H2O (neutral), thus the pH of the solution will not be changed significantly. Hemoglobin as a buffer acts in this way: At the tissues, CO2 is produced in excess and enters into the red blood cells. Inside the RBC, CO2 forms carbonic acid that dissociates into H+ and - HCO3 - 10 -  Carbonic anhydrase CO2 + H2O H2CO3 - H2CO3 H+ + HCO3 The released H+ is then buffered by hemoglobin Hb-O2 + H+ ---------- Hb.H + O2 - The bicarbonate passes to the plasma in exchange with the Cl chloride shift” - At the lungs, the reverse will happen. HCO3 enters the red blood cell in - - exchange with Cl , the H+ in hemoglobin reacts with HCO3 to form carbonic acid (H2CO3) that changes to H2O and CO2 by carbonic anhydrace enzyme. The CO2 is then released in the expired air Acid-base disorders: The pH of the arterial blood is constant at the level of 7.4 + 0.04. This is equivalent to [H+] of 40 nmol/L. pH range 7.36  7.4 7.44 [H+] range 44 nmol/L  40 nmol/L 36 nmol/L Stabilization of the pH at this range is important for the normal metabolic reactions occurring inside the cell. Deviation of the pH from this range will cause serious complications that may lead to coma and death. A pH below the normal level is referred to as acidosis, while a pH above this normal level is called alkalosis. - 11 -  The normal range of the arterial pH is controlled by 3 systems. These include : (a) Buffers. They neutralize the added acids or bases. (b) Respiratory system. It regulates the amount of carbonic acid. (c) The kidney system. It regulates he amount of bicarbonates and H+. Acidosis In health, when the kidney and the lungs are normal the ratio between bicarbonate and carbonic acid is constant at 20:1 and the pH is within normal range. [Bicarbonate] 24 mmol/L 20 _______________________ __________________________ _______ = = [Carbonic] 1.2 mmol/L 1 Acidosis is classified according to the cause into : (A) Metabolic acidosis due to primary decrease in bicarbonate concentration. (B) Respiratory acidosis due to primary increase in carbonic acid as result of CO2 retention. (A) Metabolic Acidosis: Causes: The bicarbonate level decreases as a result of the following : 1. Accumulation of non volatile acids that are buffered by bicarbonate leading to decrease in bicarbonate levels as in the following cases. (a) Uncontrolled diabetes mellitus and severe starvation. In these cases keto acids as acetoacetic acid and -hydroxybuteric acid are increased and consume a large amounts of bicarbonate to be buffered. - 12 -  (b) Administration of acidifying salt as calcium chloride or ammonium chloride. (c) Reduced excretion of acids by the kidney due to renal diseases. 2. Excessive loss of bicarbonate as in diarrhea. * Metabolic acidosis is compensated by: 1. Hyper ventilation, which is an increase in the rate and depth of respiration in order to remove more CO2 that leads to decrease in H2CO3, the ratio between bicarbonate and carbonic acid level returns to normal [20:1] and the [H becomes normal too. 2. The kidney retains the bicarbonate and decrease its loss in the urine. (B) Respiratory acidosis: It is caused by decreased rate of breathings that leads to accumulation of CO2 that change into H2CO3. CO2 + H2O H2CO3 The increase in H2CO3 will change the ratio between bicarbonate and carbonic towards acidosis. The decrease in the rate of breathing is termed hypoventilation. The cases that cause hypoventilation include: 1. Obstructive lung diseases as the bronchial asthma, and bronchopneumonia. 2. Mechanical obstruction of the air ways as in drowning, and suffocation. 3. Heart failure due to decrease in the blood going to the lungs. - 13 - 4. Drugs as Morphine, barbiturates and alcohol cause inhibition of the respiratory centre in the brain and hypoventilation. * Respiratory acidosis is compensated by the kidneys. The excretion of H+ - and the reabsorption of HCO3 by the kidney is increased to return the ratio between bicarbonate and carbonic acid levels to the normal (20:1) and the pH becomes normal. Alkalosis In alkalosis the level of bicarbonate is increased or the level of carbonic acid is decreased leading to disturbed ratio between bicarbonate and carbonic acid. [Bicarbonate] 20 ______________________ ____________ = [Carbonic] 1 The pH of the blood is increased. There are two types of alkalosis according to the causes. 1. Metabolic alkalosis due to increase in the level of bicarbonates as in: (a) Administration of large amounts of bicarbonates as during treatment of peptic ulcers or by infusion. (b) Loss of excessive amounts of HCl as in vomiting. * Metabolic alkalosis is compensated by decreasing the respiration “hypoventilation” to retain CO3 that produce more H2CO3 which can return the bicarbonate/carbonic ratio to normal (20:1) and the pH returns to normal level too. - 14 - 2. Respiratory alkalosis: * It is caused by increased rate of breathing “hyperventilation” that leads to excessive removal of CO2 by the lungs, the causes of hyperventilation include: 1. Drugs as salicylates that increase the activity of the respiratory centre. 2. Fever causes hyperventilation in a trial to reduce the body temperature through loss of heat with the expired air. 3. Hysteria. 4. Pulmonary fibrosis. * Respiratory alkalosis is compensated by excretion of the bicarbonate and retension of H+ by the kidney. - 15 -  OSMOTIC PRESSURE * If a semipermeable membrane separates two solutions, the water moves from the dilute solution to the concentrated solution. This movement of water molecule is called osmosis. * Osmotic pressure is the pressure needed to stop or prevent the osmotic flow. * Osmotic pressure can be measured by:\ 1. Osmometer 2. Changing the physical properties of a solution after osmosis as the change in melting point, freezing point. FIG (1): Osmosis is demonstrated by the following figure Water moves from (A) Diluted Solution to (B) Consented solution * Osmotic pressure is affected by the concentration of the solution and the number of particles in a solution. Biological significance of osmotic pressure: The osmotic pressure has many applications in the medical field. - 16 - 1. The normal distribution of water between the blood and intercellular space. The osmotic pressure of the plasma proteins help to absorb the water from the intercellular space to the blood capillaries at the venous end. This prevents accumulation of water between the cells “oedema”. 2. The normal kidney function depends on filtration of fluids in the glomeruli and reabsorption of fluids in the renal tubules. 3. The movement of water from outside the cell to the inside of the cell depends on the osmotic pressure inside the cells. 4. Fluids that are used for intravenous injection should be isotonic solutions as 5% glucose solution or 0.9% NaCl solution. Isotonic solution have the same osmotic power as the plasma. Hemolysis “breaking the RBCs, “occurs in hypotonic solutions having osmotic pressure less than that of the plasma. Surface Tension: * Surface tension is the force that helps the surface molecule to be held together. The molecules of a liquid at the surface are attracted by other molecules inwards and sidwards, while the molecules in the inner part of the liquid are attracted equally in all direction. This attraction between the molecules help the surface to occupy the least possible area. - 17 - * Soups, lecithin “a phospholipid” and bile salts reduce the surface tension of water. Hydrotropy : Hydrotropic substances can make a water insoluble substance as fatty acids and cholesterol more water soluble. Bile salts and phospholipids “lecithin” are examples. Bile salt help to make cholesterol in the bile more water soluble to prevent its precipitation that leads to gall stone in the gall bladder. Adsorption: Adsorption occurs when a solid particle attract and concentrate on its surface a molecules of gas, liquid, or any dissolved substance. The particles that attract other molecules are called (adsorbent particles). - The adsorbed molecules re called adsorbate. Adsorbents include: - Charcoal - Kaolin - Talc powder Characoal is used to adsorbe gases as charcoal tablets in flatulence to adsorb gases in the intestine. Characoal is used also in the masks used to adsorb toxic gases in wars. - 18 - Elution: It is the process by which the adsorbed substance is removed by a suitable solvent. Adsorption followed by elution is used as method to separate and purify substances as in chromatography. Solutions : Solutions are formed of : (a) Solutes “dissolved substance” (b) Solvents “dissolving liquid” Solutions are classified into three types 1. True solutions 2. Colloidal solutions. 3. Suspensions. The following table shows the comparison between the 3 types of solutions: True solutions Colloidal solutions Suspensions Example : Starch, protein solutions Blood cells in plasma NaCl sugar solutions Chalk powder in water. Diameter: of solute particle < 1 nm 1-200 nm >200 nm Particles cannot be seen by Can be seen by Can be seen by ordinary any microscope ultramicroscope microscope Particles can pass through They can pass Cannot pass filter paper They can pass through They cannot pass They cannot pass cellophane membrane (dialyzable) Stable Stable Unstable, sediment - 19 -  Properties of colloidal solutions Tyndall phenomenon: If colloidal is put in a dark chamber and illuminated from one side only, the colloidal particles appear as bright points. This is because the colloidal particles reflects light. This is the bases of ultra-microscope. Brownian movements: When the colloidal solution is examined by ultramicroscope, the solute particles are seen to move in a Zigzag like manner. This is due to bombardment of the solute particles with the solution. Gel-sol transformation: The semisolid state of colloids is called gel and it can be changed to sol. Or fluid state. The gel-sol transformation occurs during Imbibition and syneresis: Certain colloids like gelatin and agar-agar can keep large amounts of water. This is called imbibitions. After sometimes they expel this water out, this is called syneresis. Syneresis is observed during contraction of the blood clot expelling the serum as yellowish fluid. - 20 -  Unit (3) Carbohydrates Carbohydrates are polyhydroxy aldehydes or ketones and their derivatives or polymers. Importance: 1. Glucose is the major fuel of mammals. 55% of the total caloric requirements per day should be obtained from carbohydrates. 2. Carbohydrates enter in the structure of the cell membranes. About 5% of the cell membrane components are carbohydrates. 3. Carbohydrates enter in the structure of important compounds as glucoproteins, glycolipids, DNA, RNA, coenzymes as NAD, FAD,…. 4. Carbohydrates can be changed into triacylglycerol in the adipose tissue. Excess carbohydrates in the diet is an important cause of obesity. 5. Diseases related to carbohydrates include diabetes mellitus, glycogen storage diseases, galactosaemia, milk intolerance….. Classification: Carbohydrates are classified according to the number of saccharide units “simple units” into : 1. Monosaccharides: The molecule is formed of one sugar units. 2. Oligosaccharides “oligo= few”. On hydrolysis, the molecule produce 2-10 monosaccharide units. The most important types are the Disaccharides. 3. Polysaccharides. “poly = many” The molecule consist of more than 10 sugar units “>10 monosaccharides”. - 21 - Monosaccharides: Monosaccharides are either aldoses which contain an aldehyde group (-C=0 – H) or ketoses which contain a keto group (-C=0). They are further classified according to the number of carbon atoms in each unit into : Type Aldose Ketose 1- Triose Glyceraldehyde Dihydroxy aletone (3 carbons) CO – H H2C – OH H.C – OH C=O H2C – OH H2C – OH 2- Tetrose Erythrose Erythulose (4 carbons) CO – H H2C – OH H.C – OH C=O H.C – OH H.C – OH H2C – OH H2C – OH 3- Pentoses CO – H H2C – OH (5 carbons) H.C – OH C=O Ribose H.C – OH Ribulose H.C – OH H.C – OH H.C – OH H2C – OH H2C – OH CO – H H2C – OH H.C – OH C=O Xylose HO – CH Xylulose HO – CH H.C – OH H.C – OH H2C – OH H2C – OH - 22 - 4- Hexoses CO – H H2C – OH (6 carbons) H.C – OH C=O Glucose HO – CH Fructose HO – CH H.C – OH H.C – OH H.C – OH H.C – OH H2C – OH H2C – OH CO – H H.C – OH Galactose HO – CH HO – CH H.C – OH H2C – OH CO – H HO – CH Mannose HO – CH H.C – OH H.C – OH H2C – OH - 23 - Hexoses of physiological importance : 1. Glucose : * It is present in grapes and can be obtained by hydrolysis of sucrose, maltose, lactose, starch and glycogen. * Glucose is the main sugar of the blood. Its normal level in blood is : 70 – 110 mg/dl “Fasting level” This level increases in diseases as Diabetes mellitus. The rise of blood gluycose level above the normal is termed Hyperglycaemia. On the other hand, Hypoglycaemia is the decrease in the level of blood glucose below 70 mg/dl. * The appearance of glucose in urine is called Glycosuria. * Glucose is dextrorotatory, therefore it is sometimes called Dextrose. Dextrose solution (5%) is isotonic solution that can be given intravenously for patients. 2. Fructose: * It is present in the honey “bee honey” and in ripe fruits. It is mainly obtained by hydrolysis of sucrose “can sugar”. Inulin is a polysaccharide formed of fructose units. * Fructose can be changed to glucose in the liver and can be used in the tissues. It is the main sugar of the seminal plasma. * It is levorotatory “laevulose”. - 24 - 3. Galactose : It is obtained by hydrolysis of lactose (Milk sugar). It is used by the mammary gland to synthesize lactose of the milk. It can be changed to glucose in the liver. It is a constituent of glycolipids and glycoproteins. 4. Mannose: It is obtained by hydrolysis of plant mannans. It is a constituent of glycoproteins. Pentoses of physiological importance : 1. D-Ribose. It is found in the nucleotides as in RNA, ATP and nucleotide coenzymes as NAD, NADP and COA-SH Ribose is mainly synthesized from glucose through the hexose monophosphate pathway. 2. 2`-deoxyribose It is obtained by removal of (o) from carbon number 2 in the ribose. This process occurs during the synthesis of the deoxyribonucleatides that are used in the formation of DNA (DNA= deoxyribonucleic acid). A. Physical properties of monosaccharides: * All monosaccharides are soluble in water. * They are mostly sweet. Fructose is very sweet. Mannose is bitter. - They have one or more asymmetric carbon atom. An asymmetric carbon atom is attached to 4 different groups or atoms. The presence of asymmetric carbon atom allows: 1. Formation of isomers. 2. Optical activity. - 25 - Optical activity : If a plane polarized light passes through a solution of a monosaccharide, it deviates either to the right side (dextrorotatory (+) or d or to the left side (laevorotatory (-) or 1). Glucose is dextrorotatory “dextrose”, while fructose is laevorotatory “laevulose”. Isomers of monosaccharides: Compounds that have the same formula but differ in the spatial “space” configuration “shape” are called isomers “sterioisomers”. Types of isomerism: (I) D and L isomerism. D-sugar has its (OH) group attached to the carbon atom before the last one to the right side, while L-sugar has this (OH) to the left side. C-HO C-HO C-HO C-HO HC-OH H-C-OH HO.C-H HO.C-H H2C-OH HO.C-H H2C-OH H.C-OH H.C-OH HO.C-H H.C-OH HO.C-H H2C-OH H2C-OH D-glyceraldehyde D-glucose L-glyceraldehyde L-glucose D-Isomers of sugars are the only important forms in animals because the animal cells have enzymes that can deal with D-isomers. * D and L-isomers are mirror image and are called optical isomers. - 26 - 2. Anomers (α and ) – ring STRUCTURE The carbon atom in the aldehyde or the keto group of sugars is called anomeric carbon. This anomeric carbon may form a ring structure either with C-4 (furan) or with C-5 (pyran). If the OH group in the ring structure at the anomeric carbon is to the right side, the isomer is α and if this OH is to the left side it is called  form. H - C - OH HO - C - H H-C-OH H - C OH HO - C - H HO - C - H H - C - OH O H - C - OH O H-C H-C H - C - OH H2 - C OH α-D-glucopyranose -D-glucopyranose 3. Epimers : Epimers of glucose are isomers that differ in the configuration “shape” of –OH and –H on carbon atoms 2,3 and 4 of glucose. Galactose is an epimer of glucose since it has its OH group on C-4 at the left side. Mannose is an epimer of glucose because its OH on C2 is to the left side. 4. Aldose-ketose isomers: Glucose is aldose and fructose is a ketose, both are isomers. - 27 - B. Chemical properties of monosaccharides: 1. Reducing properties: All monosaccharides are reducing sugars due to the presence of free aldheyde or keto groups. They can reduce Benedicts reagent. Cupric hydroxide cuprous oxide (blue) (red) This property is used to detect the sugars in urine in cases of glycosuria. 2. Oxidation of monosuccharides: Oxidation of sugars gives the corresponding sugar acids. (A) Oxidation of the carbon 1 gives aldonic acids as gluconic acid from glucose. (B) Oxidation of the terminal carbon gives uronic acids. H - C - OH Oxid. at C6 Glucose glucuronic acid H - C OH * Glucuronic acid enter in the structure of HO - C H glycosaminoglycans. H - C OH O * Glucuronic acid is used to conjugate H-C C - OOH α-D-glucuronic the water isoluble materials to make them more water soluble and easily excreted. - 28 - (C) Oxidation of both C1 and C6 in Hexoses gives dicarboxylic acids. Glucose glucaric “saccharic” acid. Galactose galactaric “Mucic” acid. 3. Reduction of the aldehyde or keto groups : Reduction of the carbonyl carbon gives the corresponding alcohol : Ribose Glucose or Frultose Mannose Galactose Reduction Red Red Red H2C-OH H2C-OH H2C-OH H2C-OH H.C-OH H.C-OH HO.C-H H.C-OH H.C-OH HO.C-H HO.C-H H.C-H H.C-OH H.C-OH H.C-OH HO.C-H H2C-OH H.C-OH H.C-OH H.C-OH H2C-OH H2C-OH H2C-OH Galactitol Ribitol Sorbitol Mannitol (dulcital) * Ribitol is a constituent part of riboflavin (Vitamin B2), FMN and FAD “coenzymes” * Sorbitol production increases in patients with diabetes mellitus “DM”. Its accumulation in the eye tissues “esp. the retina” causes complication in the eye. * Mannitol is used to reduce oedema especially in the brain due to its osmotic effect. 8 Dulcitol accumulation in the lens of the eye causes cataract. - 29 - 4. Formation of sugar amines “Amino sugars”. * The – OH groups on carbon 2 of hexoses are replaced by amino group (-NH2) Glucosamine, galactosamine and mannosamine enter in the structure of glycosaminoglycans as hyaluronic acid, heparin and chondroitin sulphate. C-HO C-HO H C- NH2 H2N – C-H HO- C-H HO-C H H-C-OH H-C-OH H-C-OH H-C-OH H2C-OH H2C-OH Glucosamine Mannosamine Disaccharides : On hydrolysis, disaccharides produce 2 monosaccharide units. Lactose glucose + galactose. Maltose glucose + glucose. Sucrose glucose + fructose. The two sugar units are linked together by a glycosidic bond between C-1 in one unit and C4 or C2 in the other unit. The bond in lactose and maltose is 1 4 glycosidic bond, while in sucrose the bond is 1 2 glycoside bond. - 30 - Lactose : It is the milk sugar. It can occur in the urine of pregnant females. * It contains galactose and glucose units liked together by  1 4 glycosidic bond. * It is a reducing sugar. It is non-fermentable Sucrose : (Table sugar) * It is present in cane, beets, pinapple, sorghum and carrot roots. * It contains glucose and fructose units linked together by α-1 2 glycosidic bond. - It is non-reducing sugar since, the aldehyde and keto groups are not free. Maltose : * It is derived from digestion of starch by amylase enzyme. * It can be obtained from germinating cereals and malt. * It is formed of 2 glucose units linked together by α-1 glycosidic bond. * It is reducing. - 31 - Polysaccharides: * They produce more than 10 monosaccharide units on hydrolysis. * They are classified into 2 types: (A) Homopolysaccharides They contain one type of sugar units. They include: 1. Starch 2. Glycogen They are all made up of glucose units “glucosans” 3. Dextrins 4. Cellulose. 5. Inulin “It contains only fructose units (fructosan) (B) Heteropolysaccharides: They contain more than one type of sugar units or sugar derivatives as sugar amines, glucuronic acid or iduronic acid. The most important type of heteropolysaccharide is Glycosaminoglycan “mucopolysaccharide” which when linked to a protein in the tissue, the compound is termed Proteoglycans. (A) Homopolysaccharides 1. Starch : * It is a store of carbohydrates in plants. * It is the most important and abundant source of carbohydrates in our food. * It is found in cereals, potatoes, sweet potatoes, legums… - 32 - * Starch is formed of glucose units linked together by α-1 4 glycosidic bonds. Starch granule is formed of 2 parts, an amylase and an amylopectin. Amylose is non-branching, being formed of glucose units linked by α-1 4 bonds. Amylopectin is branching having both α-1 6 bonds at the branch point. C1 C1 C1 C1 C1 C1 C1 O O O O C4 C4 C4 C4 C4 C6 C6 C6 C6 C6 C6 C6 C1 C1 C1 O O C4 C4 C6 C6 C6 Amylose chain branch point * Starch is digested into maltose units. * Starch gives blue color with iodine. 2. Glycogen : * It is a storage form of carbohydrates in animal cells. * It is found in animal cells especially the liver cells and muscles. * Glycogen is formed of highly branched chain of glucose units linked by α- 14 bonds and α-1 6 bonds at the branch points. - 33 - * Muscle glycogen is used up by the muscle to get the energy needed for muscle contraction, while liver glycogen is changed into glucose to the blood during fasting to be used by other tissues. 3. Dextrins : They are produced during digestion of starch by α-amylase enzyme. α-amylase Starch -------------- - maltose + dextrins. 4. Cellulose : * It forms the cell wall of plant cells. * It is formed of -glucose units linked together by -1 4 glycosidic bonds. This bond cannot be digested by α-amylase enzyme in humans. Therefore cellulose cannot be digested in man. * The cellulose in the intestine forms the bulk of the stool and prevents constipation. 5. Inulin : * It is formed of fructose units. * It is found in the roots and tubers of dahlias, artichokes. * Inulin has been used for testing the kidney function “Inulin clearance”. - 34 -  (B) Heteropolysaccharides On hydrolysis, they produce more than one type of sugars, and sugar derivatives as : - Uronic acids. - Sugar amines. - Iduronic acid. - Sialic acid. - Sulphates. The types of heteropolysaccharides include : (1) Gums and mucilages. They are sticky plant exudates. They consists of a mixture of pentoses, hexoses and sugars acids with K, Ca and Mg. They are used as demulcents and emulsifiers and adhesives. * Plant guns can be sweetened and flavored and used for chewing. (2) Pectins : They are formed of galacturonic acid and other sugars. They occur in ripe fruits. They can be used as thickening agents and in drugs used in treatment of infantile diarrhea. (3) Glycosaminoglycans: They represent the most important types of the heteropolysaccharides. They include: - 35 - Hyaluronic acid: * It is formed of repeated units of glycuronic acid and N-acetyl glycosamine. [-Glucuronic acid (13) – N-acetyl glucosamine (1 4)] - Hyaluronic acid occurs in the matrix of the connective tissue, in the synovial fluids of the joints, the vitreous humour of the eye, the umbilical cord and around the mature ovum. * Importance of Hyaluronic acid: 1. It acts as a barrier in the connective tissue against invasion by bacteria. Some bacteria and the spermatozoa contain Hyaluronidase enzyme that can hydrolyse hyaluronic acid in the subcytaneous tissues that helps the bacteria to spread in the tissues and the spermatozoa to penetrate the ovum during fertilization. 2. Lubricaiton of joints. 3. It supports the eye tissue and gives the eye its form as it is present in the vitreous humour of the eye. 2. Chondroitin sulphate: * It is formed of repeated units of glucuronic acid and N-acetylgalactosamine. Sulphate groups are attached to –OH groups of the galactose. * Chondroitin sulphate occurs in the connective tissue of the cartilage, bones, joints and ligaments. (N.B., Chondro=cartilage). * Its function is to absorb the shock of the trauma as in the joints during movements. - 36 - 3. Heparin : * It is an anticoagulant produced by the mast cells. * It contains the following in its structure: - Acetyl glycosamine (90%) - L-iduronic acid (10%). - D-glucuronic acid in some forms of heparin. - Sulphates. 4. Heparan sulphate: * It is similar to heparin in structure but it contains more glucuronic (90%) and less sulphate and iduronic acid. * It is produced by endothelial cells and is attached to the cells surface by proteins (Proteoglycan). 5. Keratan sulphate: * It occurs in the corena. * It contains acetyl glucosamine, galactose and sulphate. 6. Dermatan sulphate. It occurs in the connective tissue of the skin. - 37 -  Unit (4) Lipids of Physiological Importance Definition: The lipids are organic compounds that have the common property of being: 1. Relatively insoluble in water. 2. Soluble in nonpolar solvents as ether, benzene, petroleum ether, chloroform and acetone. The lipids are related to fatty acids. Importance of lipids: 1. They are important cellular constituent in the cell membranes. They represent 75% in nerve cell membrane (75% lipids, 20% protein, 5% carbohydrates) and about 45% in other cells. Lipids in cell membranes are arranged in two layers with their polar groups facing the water on both sides of the membrane (lipid bilayer membrane). 2. Lipids are efficient source of energy. Oxidation of lipids to CO2 and H2O produces about 9.1 K cal/g., while oxidation of protein or carbohydrates produces 4.0 K cal/g for each. 3. Lipids in the adipose tissue under the skin act as thermal insulator to keep the body temperature constant. 4. Lipids in myelin sheath act as electrical insulator “non-polar lipids” to help rapid propagation of nerve impulse. 5. Lipids in adipose tissues around the internal organs support and protect these organs. 6. Lipids in our food contain the fat soluble vitamins (A,D,E,K). - 38 - Classification of lipids: Lipids are classified into : (1) Simple lipids: Esters of fatty acids with alcohols. They include: (a) Fats “Triacyl glycerol” : Esters of fatty acids with glycerol. Oils are liquid fats. (b) Waxes : Esters of fatty acids with higher alcohol. (2) Complex “conjugated lipids” They are formed of lipid part “esters of fatty acids with alcohol” and non-lipid part. They include: (a) Phospholipids: Lipids + phosphoric acid and other constituents. (b) Glycolipids: Lipids + carbohydrates. (c) Lipoproteins: Lipids + proteins “apoproteins” (d) Sulpholipids (3) Derived lipids and related compounds as fatty acids, gluycerol, sterols (as cholesterol) ketone bodies, vitamin A and its precursor “carotenes”, vitamins D, E and K. - 39 - Note : - The term Neutral Lipids is given for the uncharged lipids as Triacylglycerol, cholesterol and its ester. - Phospholipids are charged. Triacylglycerols “Triglycerides” TG They are esters of the alcohol Glycerol with 3 fatty acids H2C-OH H.C-OH R-C-OH (R-C-) H2C-OH Fattyacid Acyl group Glycerol H2C-O-C-R1 R2-C-O-C-H H2C-O-C-R3 A Triacylglycerol * Triacylglycerols could be : 1. Mixed TG : They contain different fatty acids. Nearly all the naturally occurring Triacylglycerol “in fats” are mixed (95%). 2. Simple : They contain the same acyl groups “the same fatty acids” in all the 3 ester positions. Their percentage in the naturally occurring fats is very small (5%). * Triacylglycerol could be solid at room temperature fat or liquid at room temperature oils. - 40 - Glycerol : * It is alcohol contain 3-OH groups (Trihydric alcohol) * It is soluble in water and ethanol. * It can be used in preparation of cosmetics. * It is also used in preparation of nitroglycerine which is used as vasodilator for coronary vessels. * It loses 2 H2O giving acrolein that has a pungent irritating odor by dehydration. H2C-OH H2SO4 C-H HC-OH C-H H2C-OH 2 H2O C-H2 Glycerol Acrolein Fatty Acids: * They have the general formula R – COOH Carbon chain Carboxylic group * Most of them have straight chain (R-) with even number of carbons. * They occur mainly as esters in fats and oils, and few occur as unesterified free fatty acids. * Few fatty acids are branched and few are cyclic. * Fatty acids are classified into: (A) Saturated fatty acids (they contain No double bonds) (B) Unsaturated fatty acids (they contain one or more double bonds). - 41 -  A. Saturated Fatty Acids They are classified according to the number of carbons into 2 types: 1. Short chain fatty acids. They contain 2-10 carbons. They are liquid at room temperature. They can be dissolved in water. Examples : Acetic acid CH3COOH 2 carbons Buteric acid CH3CH2CH2COOH 4 carbons Caproic CH3(CH2)4 COOH 6 carbons Caprylic CH3(CH2)6 COOH 8 carbons Capric CH3(CH2)8 COOH 10 carbon 2. Long chain fatty acids. They contain more than 10 carbons. They are solid at room temp. They are not soluble in water, but soluble in fat solvents. Examples : Pamitic CH3(CH2)14 COOH 16 carbons Stearic CH3(CH2)16 COOH 18 carbons B. Unsaturated Fatty Acids They are classified according to the number of the double bonds into : 1. Monounsaturated “Monoenoic” fatty acids. They contain only one double bond as palmitoleic and oleic acids. 2. Polyunsaturated “polyenoic” fatty acids. - 42 -  They contain two or more double bonds. The following table shows the number of carbons, the number of double bonds and the position of the double bonds in the carbon chain according to the  numbering system. Name of the fatty acid Number of carbons Number of double bonds Position of double bonds 1. Monounsaturated Palmitoleic 16 C 1 9 Oleic 18 C 1 9 2. Polyunsaturated Linoleic 18 C 2 9,12 Linolenic 18 C 3 9,12,15 Arachi donic 20 C 4 5,8,11,14 Clupanodonic 22 C 5 7,10,13,16,19 Essential fatty acids * They are polyunsaturated fatty acids. * They are very essential for normal growth and good health. * The essential fatty acids cannot be synthesized in the body and must be supplied in the food. Their deficiency in food causes diseases. * The protect the body against atherosclerosis because they form esters with cholesterol which can be easily metabolized and removed from the tissues. * The polyunsaturated fatty acids are present in large amounts in the vegetable oils as corn oil, olive oil and sunflower oil. * Arachidonic acid contains 20 carbon (eicosa) and is the origin of substances called eicosanoids. The most important eicosanoid is a substance called prostaglandin and were throught to be formed only in the prostate. They are actually formed in every tissue and they act as local hormones. The - 43 -  functions of prostaglandins are many, but the most important is the initiation of the inflammatory reactions. The enzymes needed for their synthesis are phospholipase A2 and cyclooxygenase. These enzymes are inhibited by cortisone and aspirin which are good anti-inflammatory drugs. Conjugated lipids (A) Phospholipids: They are lipids that contain phosphoric acid. The phospholipids include the following types: 1. Phosphatidic acid. * Phosphatidic acid is formed of glycerol, two fatty acids and phosphoric acid. * It is intermediate compound in the synthesis of triacylglycerol and phospholipids. 2. Lecithin “Phosphatidyl choline”. * Lecithin is formed of glycerol, 2 fatty acids, phosphoric acid and choline. * It is present in the cell membranes, the plasma, the brain and the liver. Egg Yolk contains lecithin. The importance of Lecithin : 1. Lecithin is the most abundant phospholipid of the cell membrane. 2. It represents a good store of choline which acts as source of methyl groups. HO-CH2-CH2-N (CH3)3 “choline” OH - 44 - 3. Dipalmityl lecithin reduces adhesions between the tissues especially in the lungs. Lecithin acts as surfactant in the lungs. Deficiency of dipalmityl lecithin in premature babies causes respiratory distress syndrome. The lung surfaces adhere together and the breathing becomes difficult. - Lecithinase enzyme which is present in the venoms of snakes and bees can hydrolyse the lecithin of the plasma and remove the fatty acid in position 2 to form lysolecithin. Lecithinase Lecithin lysolecithin + fatty acids. The lysolecithin is a hemolytic agent. It causes lysis of the RBC,s. 3. Cephalin “phosphatidyl ethanolamine” * It is present in brain tissue and blood plasma. * It contains glycerol, 2 fatty acids, phosphoric acid and ethanolamine (OH- CH2-CH2-NH2). * Cephalin like phospholipids contains inositol or serine instead of ethanolamine to form phosphatidyl inositol or phosphatidyl serine respectively. 4. Cardiolipin : Cardiolipin is found in the mitochondria. It contains 2 phosphatidic acids linked together by glycerol “Diphosphatidyl glycerol” cardiolipin is antigenic lipid. 5. Plasmalogen: * Plasmalogens represent about 10% of the phospholipids of the brain and muscles. - 45 - * They contain glycerol, unsaturated alcohol linked to Cl of glycerol by ether linkage, one fatty acid, phosphoric acid and ethanol amine or serine or inositol. 6. Sphingomyelins: * Sphingomyelins are found in large amounts in the brain and nerve tissue. * Sphingomyelins contain the alcohol sphingosine, one fatty acid, phosphoric acid and choline. A combination of sphingosine and a fatty acid is called ceramide. CH2-O-C-R1 CH2-FA1 CH-O-C-R2 CH-FA2 CH2-O-P-OH CH2-P – choline Phosphatidic acid Lecithin NB-P = Phosphoric acid FA = Fatty acid CH2-FA1 CH-FA CH-FA2 CH-FA CH2-P-Ethanolamine CH2P – serine Cephalin “Phosphatidyl-ethanolamine” Phosphatidyl serine CH2-FA1 CH-FA CH2-FA CH-FA2 CH-FA CH-FA CH2-P-inositol CH2-P-glycerol-P-CH2 Phosphatidyl inositol “Lipositol” Cardiolipin CH2-OH CH2-P-Choline CH-NH2 CH-NH-FA CH-OH CH-OH R R Sphingosine alcohol Sphingomyelin - 46 - CH2-O-Galactose CH-O-Oligosaccharide CH-NH-Fatty acid CH-NH-Fattyacid CH-OH CH-OH R CEREBROSIDE (galactolipid) R Ganglioside * Niemann-Picks disease is caused by hereditary deficiency of sphingomyelinase enzymes that breaks down sphingomyelins. Accumulation of sphingomyelins in the brain causes mental retardation. B. Glycolipids: They are compound lipids that contain carbohydrates. They consist of sphingosine alcohol attached to one fatty acid “ceramide” and one or more sugar units. Glycolipids include 2 types: (A) Cerebrosides. (B) Gangliosides. The fatty acid present in glycolipid are all C24 fatty acids especially in the brain. C24 fatty acids include: 1. Lignoceric 2. Cerebronic 3. Nervonic The following table shows the characteristics of cerebrosides and gangliosides. - 47 -  Cerebrosides Gangliosides Composition: SPhingosine + one fatty Sphingosine + one fatty acid + sialic acid + acid + one galactose or glucose oligosaccharide containing one glucose and 2 galactose units and sometimes, neuraminic acid. * They occur in the myelin sheath, * They occur in the nervous tissue and as brain and plasma membrane receptors in the cell membrane. * Some antigens as ABO blood group substances are formed of the oligosaccharides present in the glycosphingolipids. C. Lipoproteins : * Lipoproteins are compound lipids formed of lipids and proteins. Lipoproteins are present in the cell membrane, the mitochondria and in the blood plasma. Plasma Lipoprotein Plasma lipoproteins are composed of a protein layer called apoprotein that surround the lipids in the core. TG Apolipoprotein Cholesterol ester Phospholipids Composition of lipoprotein particle - 48 - * The non-polar lipids are located within the core, while the more polar lipids as the phospholipids and the free cholesterol are near the surface with the apoproteins. * Plasma lipoproteins are important in the transport of the water insoluble lipids from one organ to the other. Plasma lipoproteins are classified according to their densities ito the following types: 1. Chylomicrons (density