Carbohydrate Chemistry 2025 PDF

7 Carbohydrate Chemistry Carbohydrates of Biological Importance What are Carbohydrates? ▪ They are Polyhydroxy alcohols with functional aldehyde or ketol group....

7 Carbohydrate Chemistry Carbohydrates of Biological Importance What are Carbohydrates? ▪ They are Polyhydroxy alcohols with functional aldehyde or ketol group. CH2OH (Poly → many - Hydroxy → -OH - Aldehyde → H-C=O - Ketol → C = O ) H–C=O CH2OH | | H – C – OH C=O | | R R Polyhydroxyaldehydes Polyhydroxyketones ▪ Usually, the ratio between Carbon and H2O is 1, hence the name carbohydrate Classify Carbohydrates according to the hydrolysis products 1. Monosaccharides Contains Only 1 Sugar unit (Can't be Hydrolyzed). 2. Disaccharides Contains 2 sugar units. 3. Oligosaccharides Contains 3 – 10 Sugar units. 4. Polysaccharides Contains More than 10 Sugar units. 1. Monosaccharides General Formula: C n (H2O)n Classifications: A. According to the No. of Carbon atoms: Sugar No. of Carbons Includes Trioses 3 Aldotrioses and Ketotrioses Tetroses 4 Aldotetroses and Ketotetoses Pentoses 5 Aldopentoses and Ketopentoses Hexoses 6 Aldohexoses and Ketohexoses Heptoses 7 Ketoheptoses B. According to the Functional group: ᴥ Aldoses ᴥ Ketoses 1. Aldoses The Parent Aldose: is the Aldotriose Glyceraldehyde. ▪ Glyceraldehyde contains 3 Carbons: ᴥ 1st Carbon is the Aldehyde group (H – C = O). ᴥ 2nd Carbon is secondary alcohol group (H – C – OH). ᴥ 3rd Carbon is primary alcohol group (CH2OH). ▪ Glyceraldehyde may be present either in D or L forms. ▪ Theoretically higher aldoses can be formed by inserting 2ry alcohol group below the aldehyde group. 7  8 Carbohydrate Chemistry Asymmetric carbon atom: Carbon atom attached to 4 different atoms or groups. D- Glyceraldehyde L- Glyceraldehyde H–C=O H–C=O | | Formula H – C – OH HO – C – H | | CH2OH CH2OH Carbon atom before the OH to the Right OH to the Left last one (penultimate) Aldoses which are present in nature are derivatives of D-glyceraldehyde ▪ Aldoses are further Classified according to the No. of Carbon atoms into: Sugar No. of Carbon atoms Examples Aldotriose 3 D-Glyceraldehyde Aldotetrose 4 D-Erythrose Aldopentose 5 D-Ribose and D-Xylose Aldohexose 6 D-Glucose, D-Mannose and D-Galactose H–C=O H–C=O H–C=O | | | H – C – OH H – C – OH H – C – OH | | | H – C – OH HO – C – H H – C – OH | | | H – C – OH H – C – OH CH2OH | | CH2OH CH 2OH D- Erythrose D- Ribose D- Xylose H–C=O H–C=O H–C=O | | | H – C – OH HO – C – H H – C – OH | | | HO – C – H HO – C – H HO – C – H | | | H – C – OH H – C – OH HO – C – H | | | H – C – OH H – C – OH H – C – OH | | | CH2 CH2OH CH2OH CH 2OH D- Glucose D- Mannose D- Galactose 8 9 Carbohydrate Chemistry 2. Ketoses The Parent (simplest) Ketose is Dihydroxyacetone (DHA). ▪ Dihydroxyacetone contains 3 carbons. ᴥ The 2 terminal Carbons are 1ry alcohol group (-CH2OH). ᴥ The second Carbon is Ketone group (-C=O). ▪ Dihydroxyacetone has No D or L forms (Contain No asymmetric carbons). ▪ Theoretically higher Ketoses can be formed by inserting secondary alcohol group below the ketol group (between it and the 1ry alcohol group and they may be present In D or L forms (contain asymmetric carbon"s"). ▪ Naturally occurring Ketoses are mainly in the D form. CH2OH | Ketol group ry 1 alcohol groups C=O | Ketone group CH2OH Dihydroxyacetone (DHA) ▪ Ketoses are further Classified according to the No. of carbon atoms into: Sugar No. of Carbon atoms Examples Ketotriose 3 Dihydroxyacetone Ketotetose 4 D-Erythrulose Ketopentose 5 D-Ribulose and D-Xylulose Ketohexose 6 D-Fructose Ketoheptose 7 D-Sedoheptulose ▪ Sedoheptulose is the only sugar that contains 7 carbons and is formed in the body from glucose. CH2OH CH2OH CH2OH CH2OH | | | | C=O C= O C=O C=O | | | | H – C – OH HO – C – H HO – C – H H – C – OH | | | | H – C – OH H – C – OH H – C – OH CH2OH | | | CH2OH CH2OH H – C – OH | CH2OH D- Erythrulose D- Ribulose D- Xylulose D- Fructose 9 10 Carbohydrate Chemistry Special Types of isomers ▪ Optical isomers: Compounds having the same Molecular formula (same No. of atoms) but differ in the orientation of H or OH around 1 or more asymmetric carbon. Epimers: Optical isomers having more than 1 asymmetric carbon atom, all are the same only 1 is different. Examples: 1. Glucose and Mannose are epimers at C2. 2. Glucose and Galactose are epimers at C4. Annomers: Type of optical isomers represents the α and β form of any sugar in the ring structure. Examples: α, D-glucopyranose and β, D-glucopyranose. Enantiomers: The D and L forms of any sugar and they are mirror images. Example: - D-glyceraldehyde and L-glyceraldehyde. - D-glucose and L-glucose. H–C=O H–C=O | | H – C – OH HO – C – H | | HO – C – H H – C – OH | | H – C – OH HO – C – H | | H – C – OH HO – C – H | | CH2OH CH2OH D-Glucose L-Glucose Aldose – Ketose Isomers (Functional group Isomerism): ▪ Have the same molecular formula but differ in the functional group. Examples: Sugar Aldose Ketose Trioses Glyceraldehyde Dihydroxyacetone Tetroses Erythrose Erythrulose Pentoses Ribose and Xylose Ribulose and Xylulose Hexoses Glucose, Galactose and Mannose Fructose 10 11 Carbohydrate Chemistry Ring Structure of Monosaccharides ▪ Pentoses and Hexoses may be present in the Cyclic forms. ▪ This Cyclic form is due to reaction between C=O (carbonyl) of aldehyde group in aldoses or of Ketol group in Ketoses with an alcoholic hydroxyl group to form: ᴥ Furanose → 4 Carbon ring. ᴥ Pyranose → 5 Carbon ring. ▪ Haworth formula describes the cyclic structure like a ring, in this formula: ᴥ Groups which are on the Left side in the straight formula → written Upward. ᴥ Groups which are on the Right side in the straight formula → written Downward. ▪ As a result of the cyclic structure the 1st Carbon " also called Anomeric carbon or carbonyl carbon" becomes asymmetric So the sugar is present in 2 isomeric forms called Anomers: ᴥ α Form → OH is present on the Right of the anomeric carbon. ᴥ β Form → OH is present to the Left of the anomeric carbon. D-Glucose is present in 2 cyclic forms: ᴥ Furanose form → Cyclization between C1 and C4 ᴥ Pyranose form → Cyclization between C1 and C5 → D-glucopyranose is the commonest in nature. D-Fructose is present in 2 cyclic forms: ᴥ Furanose form → Cyclization between C2 and C5 ᴥ Pyranose form → Cyclization between C2 and C6 → D-fructofuranose is the commonest in nature. ▪ The smallest sugar to form ring structure is ribose and it forms ribofuranose. ▪ It should be at least 1 carbon outside the ring. 11 12 Carbohydrate Chemistry 12 13 Carbohydrate Chemistry Importance of Monosaccharides Type Example Function Pentoses Ribose - Ribonucleic acid (RNA) Formation. D2-deoxyribose -Deoxyribonucleic acid (DNA). - Main sugar of the blood. - Main source of energy to the body. Glucose (Grape’s sugar) - Present in many fruits (with fructose) - Present in all Disaccharides and many polysaccharides - Obtained by hydrolysis of Starch. Hexoses - Lactose formation (with glucose). Galactose - Milk formation. - Galactolipid formation, - Present in: Fruits with glucose. Fructose (Fruit sugar) Honey with glucose. Sucrose with glucose. Inulin. Semen (Main nutrient for sperms). Derivatives of Monosaccharides 1. Sugar Acids: Uronic Acids: ▪ Formed by oxidation of the 1ry alcohol group → Carboxyl group So; ▪ The Sugar is is converted to → Uronic acid. R R | | CH2OH COOH Monosaccharide Uronic acid Examples: Glucose Glucuronic acid (Glc UA) Galactose Galacturonic acid (Gal UA) - They are important components of polysaccharides i.e., GAGs. j 13 14 Carbohydrate Chemistry 2. Sugar Alcohols: ▪ Formed by reduction of Aldehyde group → 1ry alcohol group So: ▪ The Sugar is converted to → Sugar alcohol. H–C=O 2H CH2OH | | R R Monosaccharide Sugar alcohol Examples of Sugar Alcohols: Sugar Corresponding Function Sugar Alcohol Glucose Sorbitol Artificial Sweetener Mannose Mannitol Artificial Sweetener and medication Galactose Dulcitol Glyceraldehyde or Glycerol Present in the Structure of many Lipids: Dihydroxyacetone (Neutral Fat "TAG" and Phospholipid) Ribose Ribitol In the Structure of Riboflavin (Vit B2) Fructose Sorbitol or mannitol Clinical correlation: ▪ Sorbitol is responsible for diabetic complications. ▪ Mannitol is not reabsorbed and excreted in urine so acts as a diuretic in treatment of glaucoma and brain edema. CH2OH CH 2OH CH2OH | + 2H | | C=O H – C – OH or HO – C – H | | | R R R D-Fructose D-Sorbitol D-Mannitol CH2OH | H – C – OH | CH2OH H – C – OH | | H – C – OH H – C – OH | | CH2OH CH2OH D-Glycerol D-Ribitol 14 15 Carbohydrate Chemistry 3. Deoxy sugars: ▪ Several deoxy sugars are present in nature. Examples: D2-deoxyribose (D2-deoxyribofuranose) → in DNA. 4. Amino Sugars: ▪ Formed by replacement of OH at C2 of monosaccharide with amino group (NH2). Examples: Glucose Glucosamine Galactose Galactosamine Mannose Mannosamine Functions: ▪ They are Important components of GAGS (Glycosaminoglycans), Glycolipid and glycoproteins. ▪ Several antibiotics contains amino sugars which are important for their antibiotic activity. 5. Glycosides: Def.: Products of condensation of the anomeric carbon of the sugars with: A. Another sugar (Glycon) → Formation of disaccharides and polysaccharides. B. Non carbohydrate compound (Aglycon): as alcohols, phenols nitrogenous base. Examples: ▪ Nucleosides (found in nucleic acids) are glycosides formed of ribose or deoxy ribose and a nitrogenous base. ▪ Cardiac glycoside as digitalis contains sugar and steroid 15 16 Carbohydrate Chemistry 2. Disaccharides ▪ Consists of 2 Monosaccharides united by Glycosidic linkage. ▪ Classified according to their reducing power (Reaction with Fehling or Benedict) into: 1. Reducing disaccharides 2. Non reducing disaccharides Reducing disaccharides → with free anomeric carbon. Non reducing Disaccharide → No free anomeric carbon (both anomeric carbons are involved in the glycosidic linkage). Reducing disaccharides have α and β forms. Non reducing disaccharides have no α and β forms. Disaccharides Reducing Non-reducing Maltose Sucrose Isomaltose Lactose Reducing Disaccharides Why are they reducing? ▪ As they have Free Anomeric carbon in the 2nd sugar unit so: ▪ They are present in α and β Forms. Maltose Isomaltose Lactose Other Name Malt Sugar — Milk Sugar Structure 2 molecules of 2 molecules of β, D-Galactose D-Glucose D-Glucose and D-Glucose Linkage α1- 4 Glucosidic α1- 6 Glucosidic β1- 4 linkage linkage Galactosidic linkage Obtained by Action of Action of amylase Present in Milk amylase enzyme on starch at enzyme on the branching points starch Hydrolyzing Maltase Isomaltase Lactase Enzyme Hydrolysis 2 molecules of 2 molecules of D-Galactose and Product D-Glucose D-Glucose D-Glucose 16 17 Carbohydrate Chemistry Non-Reducing Disaccharides Sucrose: Other names: Cane Sugar, Table Sugar. Structure: α, D-Glucopyranose and β, D-Fructofuranose. Linkage: α1-2 Glucosidic linkage or β2-1 Fructosidic linkage. Present in: Cane and beets. Hydrolyzing enzyme: Sucrase. Hydrolysis Products: D-Glucose and D-Fructose. Non reducing … Explain why? Answer: As both anomeric carbons are involved in the linkage. So doesn’t have α or β forms. 3. Polysaccharides Polysaccharides Homopolysaccharides Heteropolysaccharides Contain only 1 type of Contain more than 1 type of monosaccharides monosaccharides A. Homopolysaccharides They are given names according to the building unit: Glucans: Formed of D-Glucose units and include: ᴥ Starch ᴥ Glycogen ᴥ Cellulose Fructans: Inulin: Formed of D-Fructose units and found in plants and used to assess renal (kidney) functions (inulin clearance test). 17 18 Carbohydrate Chemistry Glucans 1. Starch: It is the storage form of carbohydrate in plants. Sources: In Plants i.e., cereals (rice and wheat), legumes (beans) and tubers (potatoes). Types: Starch granules contain 2 forms: ᴥ Amylose ᴥ Amylopectin Amylose Amylopectin 15 % 85 % Inner part of starch granules. Outer part of starch granules. Linear. Branched. United by α1-4 glucosidic linkage. α1-4 glucosidic linkage and α1-6 glucosidic linkage at branching points. Hydrolyzed by α- amylase to Maltose Hydrolyzed by α- amylase to Maltose and then to D-glucose. isomaltose then to D-glucose. 18 19 Carbohydrate Chemistry 3. Glycogen: ▪ The storage form of Carbohydrates in animals. ▪ Forms 10% of the wet weight of the liver and 1-2 % of the weight of the muscle. ▪ Similar to Amylopectin but more branched. ▪ Higher molecular weight. ▪ Hydrolyzed by α-amylase to Maltose and Isomaltose then to D-glucose. 4. Cellulose: ▪ Linear Polymer of β, D-glucose. ▪ United by β1- 4 Glucosidic Linkage. ▪ Site: Plants i.e., Vegtables and Cotton. ▪ Insoluble in water. Cellulose is not digested ……Explain Why? Answer: As it can’t be hydrolyzed by amylase enzyme as amylase is specific only for the α glucosidic linkage and the linkage in cellulose is β1- 4 glucosidic linkage. Inspite of being not digested Cellulose is important in diet …… or Cellulose Prevents Constipation …… Explain Why? Answer: As it is not digested → ↑ the bulk of food → stimulates intestinal contraction→ Prevents Constipation and delay fat absorption. Don’t forget 19 20 Carbohydrate Chemistry II. Heteropolysaccharides The most important members of this group are: ▪ Glycosaminoglycans (GAGs) also called Mucopolysaccharides ▪ Proteoglycans 1. Glycosaminoglycans [GAGs] Structure: - Composed of unbranched long chain heteropolysaccharides. - Usually formed of uronic acid and amino sugar. - Unbranched and long chain more than 50 units. Classification: GAGs Sulfate Free GAGs Sulfate Containing GAGs Hyaluronic acid 1. Chondroitin Sulfate 2. Dermatan Sulfate 3. Keratan Sulfate 4. Heparin 5. Heparan Sulfate Proteoglycans Definition: GAGs which are covalently linked to a protein core. Structure: ᴥ 95 % Carbohydrates ᴥ5% Proteins Site: with other Extracellular Proteins ᴥ Extracellular matrix ᴥ Ground substance in association with extracellular Proteins Importance of GAGs and Proteoglycans 1. The negatively charged GAGs form hydrated gel and has many functions: CALLCA a. Components of Extracellular matrix. b. Attract water by osmotic pressure into the Extracellular matrix causing swelling as GAGs which is present in proteoglycans are Polyanions → bind with cations like Na+ and K+ so attract water and form hydrogen bonds with water molecules. c. Lubricant in Synovial fluid. d. Limit the passage of large molecules into Extracellular matrix allowing passage of small molecules (GAGs act as filters). 20 21 Carbohydrate Chemistry e. Compressibility of cartilage and resilience of the eyeball as cartilage is rich in proteoglycans which contain GAGs (polyanionic) as they contain water, when exposed to pressure water is squeezed out and when compression is released it regains the original hydrated size. f. Aggrecan formation. ▪ Aggrecan is the major proteoglycan present in cartilage consists of GAGs bound to a core protein. 2. Hyaluronic acid proteoglycan: Site: Extracellular matrix – soft connective tissue – synovial fluid of joints -skin – umbilical cord – vitreous humor of the eye – embryonic tissue a. Dermatology: - Aging is associated with ↓ hyaluronic acid and collagen → Loss of facial volumes and skin wrinkles. - Dermal fillers of hyaluronic acid replace lost tissue volume giving full and youthful skin. b. Rheumatology: - In osteoarthritis, the concentration of hyaluronic acid ↓ → ↓ the viscosity of the synovial fluid that protects joints against friction - Intra-articular injection of hyaluronic acid ↑ viscosity of synovial fluid →↓ friction and reliefs symptoms of arthritis. c. Ophthalmology: - The vitreous substance of the eye is composed of hyaluronic acid giving the eye gel-like characteristics which acts as a shock absorbent. - Hyaluronic acid is used in ocular surgery as cataract and lens implantation because of its protective and reconstructive nature. Hyaluronidase Enzyme (Spreading Factor): Site Function Caps of Sperms Helps Fertilization Some types of Bacteria Hydrolyzes Hyaluronic acid present in the ground substance of connective tissue So help spread of infection (spreading factor) 3. Chondroitin sulfate: - It is the most abundant GAG in cartilage, tendons, ligaments, bone and aorta. - Used in treatment of osteoarthritis. 4. Dermatan sulfate: - Present in skin, blood vessels and heart valves - Has anti-coagulant activity as it binds with heparin and ↑ its action. - ↑ The resistance to infectious diseases - Acts as anticancer drug as it interacts with growth factors and cytokines that involved in cancer formation and progression 5. Keratan sulfate proteoglycan: Important for corneal transparency. 21 22 Carbohydrate Chemistry 6. Heparin proteoglycan: Functions of Heparin: ▪ Anticoagulant → as it: ᴥ Binds factor IX and XI. ᴥ Activates Antithrombin III. ▪ Release the enzyme Lipoprotein Lipase (LPL) from the capillary wall to the plasma, this enzyme helps removal of lipids from the blood So; Heparin is called → Clearing Factor (clears blood from lipids). 7. Heparan sulfate proteoglycan: Associated with plasma membrane and important For: - Cell – cell interaction - Cell membrane receptor Mucopolysaccharidosis (MPS) ▪ GAGs are previously called mucopolysaccharides ▪ It is a group of diseases (more than 40 genetic disorder) Cause: Defect in the lysosomal enzymes needed to breakdown GAGs Effect: Accumulation of GAGs in cells, blood and connective tissues Result in: Permanent progressive cellular damage which affects appearance, physical abilities and system functions Clinical picture: BE MTHRE 1. Bone abnormalities: ▪ Coarse or rough facial features ▪ Short stature (dwarfism) ▪ Short claw like hands and joint stiffness that restrict hand mobility and functions ▪ Abnormal bone size and shape (dysplasia) 2. Enlarged organs as liver and spleen 3. Mental retardation 4. Thickened skin 5. Heart diseases (many cases) 6. Recurrent RTI (respiratory tract infection) 7. Excess body hair growth Treatment: ▪ There is no cure for this disease ▪ Physical therapy and exercise may delay joint problems and improve ability to move 22 23 Carbohydrate Chemistry Sugar substitutes (Alternative Sweeteners) ▪ Body takes carbohydrates from food, most of it converted to glucose. ▪ Cells takes glucose from the blood and use it as a source of energy. ▪ Excess sugar intake causes many health problems as glucose intolerance (Diabetes mellitus), obesity, low immunity, tooth decay, heart disease and high blood pressure ▪ Sugar substitutes taste sweet but don’t contain sugar. ▪ Sugar substitutes have same criteria of sugar, but they are undigestible, with zero or few calories, so no impact on blood glucose. ▪ Sugar substitutes include 3 categories: 1. Artificial sweeteners: ▪ Most artificial sweetener are created from chemicals in the labs, few made from natural substances like herbs. ▪ Can be 200 to 700 time sweeter than table sugar. ▪ Some researchers believe that artificial sweeteners have health hazards from weight gain to cancer (still under research). ▪ Example: Aspartame, Saccharin and sucralose 2. Sugar alcohols: ▪ Not as sweet as artificial sweeteners. ▪ Add texture and taste to foods (as in chewing gums and candy). ▪ Cause GIT (gastrointestinal) irritation like bloating gas or diarrhea. ▪ Examples: Sorbitol, Mannitol and xylitol. 3. Novel Sweetener: ▪ Derived from natural plant (plant derived non caloric sweetener). ▪ Examples: Allulose, Monk fruit, and stevia. 23