Carbohydrate Chemistry PDF 2025

2016 HISTOLOGY Biochemistry Chem Carbohydrates New Edition 2025 Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 ♥♥ Carbohydrate Chemistry ♥♥ Definition:...

2016 HISTOLOGY Biochemistry Chem Carbohydrates New Edition 2025 Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 ♥♥ Carbohydrate Chemistry ♥♥ Definition: - Organic compound (contain C,H &O) formed of polyhydroxy aldhydes or ketones derivatives. - They have general formulae Cn(H2o)n so called hydrates of carbons. )‫ ماء‬+ ‫(كربون‬ Biological importance of Carbohydrates:  Carbohydrates are the most abundant class of organic compounds in livings. 1- Give dietary calories for most organisms. 2- storage form of energy in the body. 3- Structural components. (by their own or combined with other molecules) 4- Carbohydrates in the form of fibers → Lowering blood Glucose & Cholestero l level & prevent constipation. Classification of Carbohydrates: According to number of sugar units in the total chain carbohydrates are classified to : Monosaccharides: single sugar unit, , e.g. glucose. Disaccharides: two sugar units, e.g. sucrose. Oligosaccharides ''Small multimers'' : 3 to 10 sugar units. Polysaccharides '' large multimers'' : more than 10 units, e.g. Starch & glycogen. The suffix -ose is used in biochemistry to form the names of sugars. Monosaccharides Definition: Monosaccharides are the building units of carbohydrates, they are the simplest sugars that cannot be hydrolyzed. The general formula of monosaccharides is (CH2O)n. Most common form are the hexoses (n = 6), e.g. glucose, galactose, fructose. 1|Page Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 Classification of Monosaccharides: (I) According to the presence of Aldhyde or ketone group: (Active group) (a) Aldoses: contain aldhyde group (eg: glyceraldehyde) (b) Ketoses: contain ketone group (eg:Dihydroxy acetone) a Ketone can be indicated with the suffix (ulose) (II) According to the number of carbon atoms in the backbone: Triose: contain 3 carbon atoms. Tetrose: contain 4 carbon atoms. Pentose: contain 5 carbon atoms. Hexose: contain 6 carbon atoms. Heptose: contain 7 carbon atoms. (III) According to the number of carbon atoms & active group: Number of Aldose Ketose Carbons Triose D- Glyceraldehyde. Dihydroxyacetone. Tetrose D- Erytherose. D- Erythrulose, Pentose D-Ribose, D-Xylose, D- Ribulose, D-Xylulose. Hexose D- Glucose, D- Galactose, D- Fructose. D-Mannose. Heptose D- Heptose. D- Sedohepulose. Most of the naturally occurring monosaccharides are of the D type Sedohepulose is the only sugar contain 7 Carbon in the body formed from glucose. Biological importance of monosaccharides: 1- Trioses: Glyceraldehyde 3-phosphate & dihydroxyacetonephosphate are intermediates during glucose oxidation in living cells. 2- Tetroses : Erythrose 4-phosphate is formed during glucose oxidation. 3- Pentoses : - Ribose is component of ribonuclic acid (RNA). 2-Deoxyribose is a component of deoxyribonuclic acid (DNA). 2|Page Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 4- Hexoses :  i) D-glucose ( grape sugar): Main sugar present in blood & present in all animal and plant honey and fruits. Formation of disaccharides (sucrose) and polysaccharides (starch). It is also termed dextrose because it is dextrorotatory.  ii) D-galactose: Formation of lactose which is present in milk. Found in glycosaminoglycans (GAGS), glycolipids and glycoproteins. iii) D-fructose (fruit sugar): Present in honey, fruits and semen. Formation of sucrose and inulin. It is also termed levulose because it is levorotatory.  Physical properties of monosaccharides:  Asymmetric carbon ”Chair Carbon”:  A carbon atom that attached to four different chemical groups. All monosaccharides contain one or more asymmetric carbon atom (except Dihydroxyacetone which contain no asymmetric carbon atom).  Any substance contains asymmetric carbon atom show 2 properties: - Isomerism. - Optical activity. 3|Page Dr. Ma7moud El7efnawy ‫‪Carbohydrate Chemistry‬‬ ‫‪Biochemistry‬‬ ‫‪2025‬‬ ‫قواعد رسم أى سكر للفهم اكتبها ورايا فى الحصة (الفيديو)‬ ‫‪Aldoses‬‬ ‫‪- The parent of aldoses is the aldotriose : (Glyceraldhyde).‬‬ ‫‪- Glyceraldhyde contains 3 Carbon (Triose) :‬‬ ‫‪ The first is aldhyde group (H-C=O).‬‬ ‫‪ The second carbon is secondary alcohol (H-C-OH).‬‬ ‫‪ The third carbon is primary alcohol (CH2OH).‬‬ ‫‪- Glyceraldhyde may be present in D or L form.‬‬ ‫‪- Higher aldoses can be formed by adding secondary alcohol below aldhyde‬‬ ‫‪group.‬‬ ‫اليمي ⇨ ‪D‬‬ ‫ر‬ ‫االخية مرسومة اتجاه‬ ‫ر‬ ‫الهيدركسيل ف الكربونة قبل‬ ‫االخية مرسومة اتجاه اليسار ⇨ ‪L‬‬ ‫ر‬ ‫الهيدركسيل ف الكربونة قبل‬ ‫‪ -‬باختصار كده الجليرسالدهيد هو ابسط واحد ف السكرات االلدوز ‪ ,‬النه يحتوى عىل اقل‬ ‫عدد من الكربونات ممكن تتواجد ف السكر ‪ ,‬الىل ىه ‪ 3‬كربونات ‪.‬‬ ‫ن‬ ‫نوعي بق ‪:‬‬ ‫‪ -‬الكربونة لو فيها هيدروكسيل تسىم كحول ‪ ,‬بس عندى‬ ‫هيدروجي بسميه برايمرى )‪1- primary alcohol (CH2OH‬‬ ‫ر‬ ‫اتني‬ ‫لو فيها ر‬ ‫هيدروجي واحدة بسميها سكندرى )‪2- secondary alcohol (H-C-OH‬‬ ‫ر‬ ‫لو فيها‬ ‫اكي من الجليرس الدهيد "نظريا" هيود سكندرى الكحول تحت‬ ‫‪ -‬عشان ترسم اى الدوز ر‬ ‫الكربونة األوىل (االلدهيد)‬ ‫‪4|Page‬‬ ‫‪Dr. Ma7moud El7efnawy‬‬ Carbohydrate Chemistry Biochemistry 2025 Ketoses - The parent of ketoses is the ketotriose : (Dihydroxyacetone). - Dihydroxyacetone contains 3 Carbon (Triose) :  The first is primary alcohol (CH2OH).  The second carbon is ketone (C=O).  The third carbon is primary alcohol (CH2OH). - Dihydroxyacetone has no D or L form. (No asymmetric carbn !!!) - Higher Ketoses can be formed by adding secondary alcohol below ketone group. (they may present in D or L). ‫هتفهم السطر ده بعد شوية متقلقش يا دكتورنا العزيز‬ D or L‫االخية عشان كده مفيش‬ ‫ر‬ ‫مفيش هيدركسيل ف الكربونة قبل‬ ‫ النه يحتوى‬, ‫هيدروكس اسيتون هو ابسط واحد ف السكرات الكيتوز‬ ‫ي‬ ‫ باختصار كده الداى‬-. ‫ كربونات‬3 ‫ الىل ىه‬, ‫عىل اقل عدد من الكربونات ممكن تتواجد ف السكر‬ ‫اكي من الداى هيدروكس اسيتون"نظريا" هيود سكندرى‬ ‫ عشان ترسم اى كيتوز ر‬-.)‫الكحول تحت الكربونة التانية (الكيتون‬ 5|Page Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025  Ring form of monosaccarides: ‫للفهم‬ Many simple sugars can exist in an open chain form or ring form. Ring is favored in aqueous solution. There are two forms of ring form: (a) Furanose ring formed of 4 carbons & one oxogyn. (b) pyranose ring: formed of 5 carbons & one oxogyn.  The aldehyde group can combine with hydroxyl group of carbon atom and form hemiacital linkage.  The ketone group can combine with hydroxyl group of carbon atom and form hemiketal linkage. In aldohexoses: - Furanose ring is between C1 C4 - Pyranose ring is between C1 C5 Aldose tend to form Pyranose ring If (OH) group at carbon 1(anomeric carbon) is:  on the right side this is called ɑ form.  on the left side it is called β form. In Case of D-Glucose Glucose solution contains 1/3 𝜶 form & 2/3 𝜷 form and traces in the aldhyde form at 20°, aldhyde form is formed during conversion between two forms. 6|Page Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 In Ketohexoses: - Furanose ring is between C2 C5 - Pyranose ring is between C2 C6 Ketohexoses tend to form furanose ring. If (OH) group at carbon 2 (anomeric carbon) is on:  the right side this is called ɑ form.  the left side it is called β form. In case of D-Fructose: It is present in two cyclic forms:  Furanose is formed due to the cyclization between C5 and C2, and it is present in the disaccharide (sucrose) and polysaccharide (inulin).  Pyranose is formed due to the cyclization between C6 and C2, and it is present in this form when it is free in solution. In case of D-Ribose: cyclization occurs between C4 and C1 ⇨ribofuranose ♠ Anomeric carbon atom ‫مهم نظرى‬ C1 in aldoses & C2 in ketoses are symmetric carbon atom, but after ring formation they become asymmetric. ♠ Haworth projection formula: ‫قراءة للفهم‬ - It is a hexagon with its oxygen atom at the upper right hand corner. - Carbon atoms numbered clockwise. - Groups attached to right hand side → found below the plane of the ring.(down) - Groups attached to left hand side → found above the plane of the ring. (up) - The terminal CH2OH is always above the plane of the ring. (up). 7|Page Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025  Isomerism: ☺☺  Isomers: They are compounds having the same molecular formula (same number of carbon, hydrogen, oxygen) but different structural or steric formulae. ‫بيختلفوا عن بعض فى المجموعات الكيميائية أو توزيعها‬  Stereoisomers: They have the same molecular formula and sequence of atoms, but differ in the three-dimensional orientations of their atoms in space. ‫بيختلفوا عن بعض فى توزيع المجموعات فقط‬ ♠ They mainly depend on Asymmetric carbons. ♠ Number of steroisomers of any sugars = 𝟐𝒏 ( n= number of asymmetric carbons atoms) ♠ Number of asymmetric carbon of any sugars atoms = (number of aldose carbon atom - 2) or (number of ketose carbon atom - 3) ♠ Glucose which is an aldohexose contain 6 carbon atoms, so has 4 asymmetric carbon atoms (6-2=4) so has 16 steroisomers (24 =16). ♦Types of Stero-isomers : (4 types) (a) Enatiomars (D & L isomerism). (b) Epimers. (c) Anomers (ɑ & β isomerism). (d) Functional group Isomerism. (a) Enatiomars (Optical isomer “D & L isomerism”) They are steroisomers which differ in the distribution of (H) & (OH) group around the Penultimate “subterminal”carbon atom (before the last).asymmetric carbon atom. If (OH) group to the right of sub terminal atom → (D- form) eg: D-glyceraldehyde. If (OH) group to the leftt of sub terminal atom → (L- form) eg: L-glyceraldehyde This difference make the two forms mirror image to each others. They are called Enatiomars. ♠ Almost all naturally occurring Carbohydrates are of D-configuration. 8|Page Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 (b) Anomers (ɑ & β isomerism) 7 & 6 ‫انظر صفحة‬ (cyclic structure of monosaccharides): They are steroisomers which differ in the distribution of (H) & (OH) group around the asymmetric anomeric carbon atom. Anomeric carbon atom: C1 in aldoses & C2 in ketoses are symmetric carbon atom, but after ring formation they become asymmetric. If (OH) group at anomeric carbon is on: - the right side (below the plane) this is called ɑ-form. - the left side (above the plane ) it is called β form. eg: ɑ-Glucose & β-Glucose. N.B: α and β forms can interconvert in solution ( mutorotation): equilibrium 66% β, 33% α, 1% open chain. ‫من أول هنا نظررررى‬ (c) Aldose-Ketose Isomers (Functional Group Isomerism): They are isomers that have the same (molecular formulae) carbon skeleton, the same position of substituent group, but have different functional groups (aldehyde or ketone). Glyceraldehyde & Dihydroxyacetone For example: Fructose is a ketohexose has a molecular formula C6H12O6 is a functional group isomer for any aldohexose (has the same molecular formula C6H12O6) e.g. glucose, galactose and mannose. 9|Page Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 b) Epimers: They are compounds which have more than one asymmetric carbon and differ only in the configuration of (H) & (OH) group around : Single asymmetric carbon atom other than the anomeric carbon (C1 in aldoses or C2 in ketoses) and the subterminal carbon (D & L creating carbon). Examples: Glucose and mannose are epimers at C2. Glucose and galactose are epimers at C4. Ribose and xylose are epimers at C3 Ribulose and xylulose are epimers at C3 Anomers are epimers at C1 of cyclic aldoses and C2 of cyclic ketoses. : ‫ركز كده فى الكام جملة الجاييين‬ As : galactose C4 OH at left side and Glucose C4 OH at right side. Mannose C2 OH at left side and Glucose C2 OH at right side. ♠ Glucose is an epimer to each of mannose & galactose. ♠ Mannose and galactose are not epimer to each others. 10 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 Monosaccharide derivatives 1- Sugar acids: (by oxidation) The primary alcohol of (CH2OH) are oxidized ⇨ carboxyl group (COOH) with oxidizing agents → Sugar acid formation. Sugar is converted to uronic acid. They are important component of polysaccharides i.e. GAGs ‫ عند اكسدة الهيدروكسيل تتحول لكربوكسيل و هى‬,‫األكسدة تعنى اضافة أكسجين أو ازالة هيدروجين من المركب‬- (CH2OH ⇨COOH).‫ يبقى السكر اصبح سكر حمضى ل احتواءه على الكربوكسيل‬,‫المجموعة المميزة لالحماض‬ uronic acid ‫ عند اكسدة الكربونة االخيرة فى اى سكر يتحول لحمض ينتمى لعائلة تسمى‬-  Glucose is oxidised ⇨ glucuronic acid (GlcUA).  Galactose is oxidised ⇨ galacturonic acid (GalUA). : ‫اضف الى معلوماتك‬ uronic ‫اكسدة أخر كربونة فقط تعطى عائلة ال‬  aldonic ‫اكسدة أول كربونة فقط تعطى عائلة ال‬  Saccharic ‫اكسدة األولى و االخيرة تعطى عائلة ال‬  Vitamin c (L-ascorbic) is sugar acid  2- Deoxy sugar: These are sugars in which the hydroxyl group of C2 is replaced by a hydrogen atom. The most important examples are: Importance: 2-Deoxy ribose enter in the structure of DNA.. ‫ فاصبح كأننا ازالنا اكسجين‬, ‫ و حطينا مكانها هيدروجين فقط‬2 ‫شيلنا الهيدروكسيل اللى فى الكربونة رقم‬ 11 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 3-Sugar alcohol: (by Reduction) Reduction of monosaccharides gives sugar alcohol. Reduction can occur to carbonyl group (functional group) to alcohol group. : ‫ عند اختزال الكيتون أو االلدهيد يعطى كحول‬,‫االختزال يعنى اضافة هيدروجين أو ازالة اكسجين من المركب‬ -Ketone (C=O) → Secondary Alcohol (H-C-OH) -Aldehyde (H-C=O) → Primary alcohol (CH2-OH)  Examples & Importance of Sugar alcohols: Ribose reduction → Ribitol that is a part of structure of vitamin B2 (Riboflavin) Glucose reduction → Sorbitol that enter in Artificial sweeteners.. Galactose reduction → dulcitol that enter in Artificial sweeteners. Mannose reduction → manitol that enter in Artificial sweeteners. Glyceraldhyde & Dihydroxyacetone reduction → Glycerol that enter in structure of many lipids as neutral fat (TAGs) & Phospholipids. Fructose reduction → Sorbitol or manitol. The reduction of ketones produces 2 epimeric alcohols..asymmetric ‫ و بالتالى الكربونة دى هتبقى‬primary alcohol ‫ الكيتون بتتحول ل‬- ‫ قولنا الحصة للى فاتت ان البرايمرى دى لو اتحط الهيدركسيل يمين تدى مركب و لو اتحطت شمال‬-.‫تصبح مركب تانى فلو حطينا الهيدروكسيل يمين اصبح سوربيتول و لو اتحطت شمال اصبح مانيتول‬ 12 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 Importance of mannitol: Mannitol is low caloric sweetener as it is poorly absorbed. Mannitol is not metabolized and easily handled by tissues as: - Kidney ( used as diuretics). - Eye (reduce eye pressure in glaucoma). - Brain (lower intracranial pressure in brain oedema). 4- Amino Sugar: They are produce by replacing (OH) group on C2 by amino group (NH2). e.g. D-Glucose → D-Glucosamine , D-Galactose → D-galactoseamine Importance of Amino sugar: 1- Formation of GAGAs, glycoproteins & glyolipids. 2- Some antibiotics contain amino sugars such as erythromycin. 5- Ester formation: (acid + alcohol = ester) The hydroxyl groups of monosaccharides with acids ⇨ esters , for examples: 1- Phosphate esters: glucose 1-P and glucose 6-P. 2-Sulfate esters: present in GAGs & glycolipids (sulfolipids) e.g. 𝛽-D galactose 3-sulfate. 5- Glycosides: (monsaccharides + other) Glycosides are products of condensation of the anomeric carbon of the sugar with: 1) Another sugar (Glycon): e.g. formation of disaccharides and polysaccharides. 2) Non-Carbohydrate compound (Aglycon): such as alcohols, phenols or nitrogenous bases. The glycosidic linkage is named according to the anomeric carbon to which it is attached (𝜶&𝜷) and according to the parent sugar e.g. glucosidic, galactosidic or fructosidic bond. Examples of glycosides: Nucleoside: glycoside of ribose or deoxy ribose + nitrogenous base. Cardiac glycoside : digitalis: sugar + (aglycon) steroid. 13 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 II- Disaccharides  They are formed by condensation of 2 monosaccharides.  The bond between them is called glycosidic bond (O-glycosidic).  The glycosidic linkage is named according to the carbonyl carbon to which it is attached (α & β) and according to the parent sugar e.g., glucosidic, galactosidic or fructosidic bond.  There are two types of disaccahrides: Reducing: Non- reducing: (e.g. sucrose) ‫هنا انا هوصل انوميرك بتاعت سكر بأى كربونة فى السكر التانى بشرط‬ ⇦‫هنا انا هوصل انوميرك بتاعت سكر باالنوميرك بتاعت السكر التانى‬ ‫متكونش االنوميرك بتاعت التانى ⇦ كده عندى انوميرك فاضية و التانية‬.‫كده مفيش انوميرك فاضية و االتنين مرتبطتين ببعض‬ (e.g. lactose and maltose, isomaltose). ‫مرتبطة‬ 1- Maltose 2-Lactose 3-Isomaltose 4-Sucrose (Malt sugar) (Milk sugar) (Cane or Table sugar) Formed of two glucose 2 glucose Formed of Fructose and Formed of united by α-l,4- united by α-l,6- Glucose united by: galactose and glucosidic linkage. glucosidic α l ,2-glucosidic linkage glucose united linkage. or by β1 ,4- β2,l -fructosidic galactosidic linkage. linkage. It is hydrolyzed by It is hydrolyzed hydrolyzed by It is present in plants as maltase enzyme or by by lactase isomaltase sugar cane and beets. acids into two enzyme or by into 2 glucose. molecules of D-glucose. acids into glucose and galactose. obtained by the Main product of Both carbonyl carbons action of amylase enzyme digestion of starch by on starch at are involved in the amylase. branching linkage, so sucrose is point. non-reducing - 14 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 III- OLIGOSACCHARIDES  Polymers of 3-10 monosaccharide units.  Present as a constituent of many types of glycolipids and glycoproteins e.g., oligosaccharides which are constituent of ABO blood group substance and immunoglobulins.  Not an important in diet for humans as most are nondigestible. IV-POLYSACCHARIDES They are composed of more than 10 monosaccharides linked by glycosidic bond. They are non reducing because there will be leaving only one free carbonyl group at the end of a big molecule They are two types : (1) Homopolysaccharides: formed of only 1 type of monosaccharide. (2) Heteropolysaccharides: contain more than one types of monosaccharides. Homopolysaccharides  They are made up of only one type of monosaccharide units.  They are given names according to the building unit: 1. Glucans: formed of D-glucose units and include starch, dextrins, glycogen and cellulose. 2. Fructans: formed of D-fructose units e.g inulin present in plants, and used to assess renal function. 1- Starch:  Starch is the chief storage form of carbohydrates in chlorophyll- containing plants.  It is present in large amounts in cereals (rice and wheat), tubers (potatoes and sweet potatoes) and legumes (beans).  Starch granules contain two forms: Amylose Amylopectin linear unbranched molecule with branched molecule with: αl,4-glucosidic bonds connecting the - αl ,4-glucosidic bonds connecting the glucose glucose units units - within the branches, and al ,6-glucosidic bonds at the branching points. 15-20% inner part 80-85% outer part 15 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 2- Glycogen:  Storage form of carbohydrates in animals (animal starch).  It is present in most cells but specially in skeletal muscles (1-2% of weight) and liver (10% of weight). (as stores of excess glucose).  It is a highly branched molecule (more branched than amylopectin); glucose units are connected by: - αl ,4-glucosidic bonds within the branches. - and αl ,6-glucosidic bonds at the branching points. 3- Cellulose:  Cellulose forms the principal part of the cell wall of plants.  It is formed of a long non-branched chain of (β-glucose units connected by βl ,4-glucosidic linkage.  Partial hydrolysis by cellulose → cellobiose (reducing disaccharides). Clinical Correlation: - Cellulose is insoluble in water. - It is non-hydrolysable by amylase digestive enzyme because this enzyme hydrolyzes only α- linkages. - Undigested cellulose in diet is important as it increases the bulk of food, which stimulates intestinal contractions → prevents constipation. - Also, cellulose in diet delays fat absorption B - Heteropolysaccharides  These are polysaccharides which are formed of more than one type of monosaccharide unit.  They include glycosaminoglycans (GAGs) formerly called mucopolysaccharides. 16 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 Glycosaminoglycans(GAGs) Glycosaminoglycans are:  Unbranched  Long chains (usually >50 sugar units) heteropolysaccharides  Composed of repeating disaccharide units (an amino sugar & auronic acid). Glycosaminoglycans are classified into: I. Sulfate free (non sulfated) glycosaminoglycans: e.g. hyaluronic Acid II. Sulfate containing glycosaminoglycans:e.g. - Chondroitin sulphate - Dermatan sulphate. - Keratansulphate. - Heparin. - Heparan sulphate. Types structure site Hyaluronic acid glucuronic acid +N acetyl- Synovial fluid, skin, cartilage, (HA) glucosamine vitreous..etc. Chondroitin glucuronic acid + N-acetyl- Cartilage, tendon, ligaments, bone, sulfate (CS) galactosamine sulfate. aorta. (most abundant GAG) Dermatan sulfate L-iduronic acid +N-acetyl- skin, blood vessels and heart valves (DS) galactosamine sulfate Keratan sulfate galactose +N-acetyl-glucosamine cornea (KS) sulfate (No uronic acid) L-iduronic (D glucuronic) acid-- Heparin sulfate + glucosamine bisulfate Heparan sulfate -More glucuronic acid. cell membrane - its glucosamine residue contains less sulfate than heparin. proteoglycans - Definition: GAGs which are covalently conjugated to a protein core. - Structure: 95% Carbohydrates + 5% Proteins. - Site: extracellular matrix (ECM) or ground substance in association with other extracellular proteins. 17 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 Functions of GAGs and proteoglycans: 1- Compnent of extracellular matrix. 2- GAGs are negatively charged polyanioins (Due to negatively charged carboxylate and sulfate groups on the proteoglycan) → bind with positively charged ions (cations) help it to trap water molecules → form a hydrated gel which: - Provides flexible mechanical support for the extracellular matrix - Acts as a filter that allows the diffusion of ions (e.g., Ca2+). - Acts as a lubricant in synovial fluid. - Is compressible:  When a GAG (polyanionic) solution is compressed ⇨ water is squeezed out and GAGs occupy a smaller volume.  When the compression is released ⇨ their molecules regain their original hydrated size. This explains their role as shock absorbents in joints and making the eyeball resilient. 3- Chondroitin sulfate: is the most abundant GAG It is commonly used as an oral treatment for osteoarthritis. 4- Dermtan sulfate: Maintenance structure & shape of sclera of the eye. Anticoagulant activity as it binds to heparin →↑ its action. ↑resistance to infectious disease Potential anticancer drug as it interacts with growth factors & cytokines enter in cancer formation. 5- Heparin: function of heparin: a. Heparin is anticoagulant (prevents thrombus formation) as:  It acts by binding with factor IX and XI.  Also, it produces activation of antithrombin III. b. Release lipoprotein lipase enzyme form the capillary wall to the plasma ⇨ removal and clearance of blood lipids ⇨ so Heparin is called clearing factor. 6- Keratan sulfate: Important for corneal development and maintenance of its transparency ‫قرنية العين‬ 18 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 7- Heparan sulfate proteoglycans:‫التواصل بين الخاليا و بعضها‬ cell membrane receptors and cell-cell interactions. 8- Hyaluronic acid : Importance of hyaluronic acid in: a- Dermatology: Hyaluronic acid & collagen decreases with aging →↓ hydrating gel →loss of facial volume and appearance of wrinkles. Dermal filler of hyaluronic acid → replaces lost tissue volume→ giving full youthful skin. ‫بشرة شبابية‬ b- Rheumatology: In osteoarthritis:  Hyaluronic acid concentration gradually decreases →↓ viscosity of synovial fluid which protects joints from friction.  Intra-articular hyaluronic acid →↑ viscosity of synovial fluid →↓friction & relieving painful arthritic symptoms. c- Ophthalmology The vitreous substance of eye is composed completely of hyaluronic acid → giving its viscous gel like character (act as shock absorber for the eye and transports nutrients to tissues). Hyaluronic acid is used during ocular surgery, cataract extraction & lens implantation because of its protective and reconstructive nature. Age related pain may devolp in old age ?? Due o replacement of hyluronic acid y dermtan sulfate in synovial fluid, dermtan is not good lubricant. Hyaluronidase enzyme (spreading factor): - Hydrolyze hyaluronic acid in the ground substance of connective tissue. - Hyaluronidase secreted by: a) Some bacteria ⇨ spread of bacteria through subcutaneous tissue. ‫يساعد البكتريا على االنتشار بين الخالاايا‬ b) Sperms (head) ⇨ helps the process of ovum fertilization. ‫يساعد الحيوانات المنوية على اختراق البويضة‬ 19 | P a g e Dr. Ma7moud El7efnawy Carbohydrate Chemistry Biochemistry 2025 Mucopolysaccharidosis: ‫اسم مجموعة من االمراض‬ Group of metabolic disorders (40 genetic disorders) caused by absence of defect of lysosomal enzymes needed to break down GAGs →accumulation of GAGs in cells, blood and connective tissue → permanent progressive cell damage which affects appearance, physical ability and system functions. Clinical picture: 1- Bone abnormalities:  Coarse, rough facial features.  Short stature (dwarfism).  Short claw like hands, joint stiffness → restrict hand mobility & function.  Abnormal bone size and shape (dysplasia). 2- Thick skin, excessive body hair growth. 3- Enlarged organs as spleen or liver. 4- Mental retardation 5- Respiratory tract infection 6- Heart disease. Treatment: “No cure for these disorders. (Enzymatic deficiency) “ - Physical therapy & daily exercise may delay joint problems & improve movement. - Enzyme replacement therapy may be useful. - New treatment under trials. Dr. Mahmoud El7efnawy 20 | P a g e Dr. Ma7moud El7efnawy