Biochemistry Carbohydrates (1-6) PDF - First Year Medicine 2024-2025

# Biochemistry ## Chapter 1 ## Carbohydrate Chemistry ### First year medicine ### 2024-2025 ### د. إيمان الشيخي ### Reference books: 1. Oraby's Illustrated review of Biochemistry part I, part II and part III. 2. Lippencot's Illustrated review of Biochemistry 3. Harpper's Illustrated Biochemistry ## Biochemistry: Is the chemistry of molecules found in living organisms, such as protein, lipid, nucleic acids and carbohydrates. ## Carbohydrate ## Definition: Carbohydrates are aldehyde or ketone derivatives of polyhydric alcohols (e.g. glycerol) or any substance derived from them. - CH2OH - H-C-OH - CH2OH Glycerol - A Aldehyde group - OH - C - H-C-OH - CH2OH Glyceraldehyde - Glycerol - B Keto group - CH2OH - C=O - CH2OH Dihydroxyacetone ## Importance of Carbohydrates Carbohydrates constitute about 60% of our diet. They are important for: - Energy production, e.g. glucose. Brain cells and RBCs are almost wholly dependent on carbohydrates as the energy source. - Glycogen can be stored in the muscles and liver and later used for energy. - Fibers are important for intestinal motility and waste elimination. - Glycolipids or glycoproteins; both enter in the structure of cell membrane and form the ground substances between tissues. ## Sources of Carbohydrates 1. Starchy food such as potatoes, pasta and grains. 2. Vegetables. 3. Milk and milk products. Animals, including humans, cannot synthesize carbohydrates from carbon dioxide and water and are therefore dependent on the plant kingdom to provide these vital compounds. We use carbohydrates not only for food but also for clothing, fuel, and paper. ## Classification of Carbohydrates - **Monosaccharides:** Contain 1 monosaccharide units - **Disaccharides:** Contain 2 monosaccharide units - **Oligosaccharides:** Contain 3-10 monosaccharide units - **Polysaccharides:** Contain more than 10 monosaccharide units ## Monosaccharides (glycoses) They are the simplest units of carbohydrate i.e. on hydrolysis, they cannot give a simpler form. The general formula is Cn (H2O)n. ## Naming (nomenclature) of monosaccharides: ### I) According to the presence of aldehyde or ketone group: - **Aldoses:** Monosaccharides containing aldehyde group. - **Ketoses:** Monosaccharides containing ketone group on the second carbon atom. - A Aldehyde group - OCH - H-C-OH - CH2OH Glyceraldehyde - B Keto group - CH2OH - C=O - CH2OH Dihydroxyacetone ### II) According to the number of carbon atoms: Monosaccharides of specific sizes may be indicated by names composed of a stem denoting the number of carbon atoms and the suffix -ose. - **Trioses:** Monosaccharides containing 3 carbons. - **Tetroses:** Monosaccharides containing 4 carbons. - **Pentoses:** Monosaccharides containing 5 carbons. - **Hexoses:** Monosaccharides containing 6 carbons. - **Heptoses:** Monosaccharides containing 7 carbons. ### III) According to both presence of aldehyde or ketone groups and number of carbon atoms: Combining the classification systems (I and II) gives general names that indicate both the type of carbonyl group and the number of carbon atoms in a molecule. - Aldotrioses and ketotrioses. - Aldotetroses and ketotetroses. - Aldopentoses and ketopentoses. - Aldohexoses and ketohexoses. ## Classification of monosaccharides ### 1) Triose: Monosaccharides containing 3 carbons: - **Aldotrioses:** Glyceraldehyde “glycerose”. - **Ketotrioses:** Dihydroxyacetone. - A Aldehyde group - OH - C - H-C-OH - CH2OH Glyceraldehyde - B Keto group - CH2OH - C=O - CH3 - C = O - CH3 Acetone Not carbohydrate - CH2OH Dihydroxyacetone ### 2) Tetroses: Monosaccharides containing 4 carbon atoms: - **Aldotetroses:**Erythrose. - **Ketotetrose:** Erythulose - H-C=O - H-C-OH - H-C-OH - CH 2OH - CH2OH - C=O - H-C-OH - CH2OH ### 3) Pentoses: Monosaccharides containing 5 carbon atoms: - **Aldopentoses:** Ribose, deoxyribose, arabinose, xylose - **Ketopentoses:** Ribulose and xylulose. |Aldoses | Ketoses| |:---|:---| | H2C=O H-C-OH H-C-OH H-C-OH H-C-OH CH2OH D - Ribose| CH2OH C=O HO-C-H H-C-OH H-C-OH CH2OH D‐Ribulose | H2C=O H-C-OH H-C-H H-C-OH H-C-OH CH 2OH D‐Deoxyribose| CH 2OH C=O HO-C-H H-C-OH H-C-OH CH2OH D‐Xylulose | H2C=O H-C-OH H-C-OH H-C-OH H-C-OH CH2OH D-Xylose| importance function) or pentoses: - Ribose and deoxyribose enter in the structure of nucleic acids RNA and DNA. - Ribose enters in the structure of ATP, GTP and other high energy phosphate compounds. - Ribose enters in the structure of coenzymes NAD, NADP and flavoproteins. - Ribose phosphate and ribulose phosphate are intermediates in pentose phosphate pathway - Xylulose is an intermediate in uronic acid pathway. ### 4) Hexoses - **Aldohexose:** glucose, mannose and galactose. - **Ketohexose:** fructose. |Aldoses | Ketose | |:---|:---| | H2C=O H-C-OH HO-CH H-C-OH H-C-OH CH2OH D-Glucose| CH2OH C=O HO-CH H-C-OH H-C-OH CH 2OH D-Fructose | H2C=O H-C-OH HO-CH H-C-OH H-C-OH CH2OH D-Mannose| | H2C=O H-C-OH HO-CH H-C-OH H-C-OH CH2OH D-Galactose| ### Importance of hexoses: - Although a variety of monosaccharides are found in living organisms, three hexoses are particularly abundant: D-glucose, D-galactose, and D-fructose #### Glucose: (also known as Dextrose, blood sugar and corn sugar ) - Is the most abundant sugar found in nature. - Most of the carbohydrates we eat are eventually converted to it in a series of biochemical reactions that produce energy for our cells. - Main sugar of blood. - Major source of energy in mammals - In the liver and other tissues, glucose is converted to all carbohydrates in the body e.g. glycogen, galactose, ribose and fructose. - H - C - H-C-OH - HO - C-H - H - C-OH - H-C-OH - CH 2OH Glucose (an aldohexose) #### Fructose “fruit sugar": - Is the most abundant ketohexose. - It can be converted into glucose in the liver. - It occurs, along with glucose and sucrose, in honey (which is 40% fructose) and sweet fruits. - Fructose (from the Latin fructus, meaning "fruit"). - Fruits contains high fructose content. - It is the main sugar of semen. - CH2OH - C=O - H-C-OH - H-C-OH - CH2OH Fructose (a ketohexose) #### Mannose: - A constituent of many glycoproteins. #### Galactose: - D-Galactose does not occur in nature in the uncombined state. - The galactose needed by the human body for the synthesis of lactose is obtained by the metabolic conversion of D-glucose to D-galactose. - It can be converted into glucose in the liver. - It is synthesized in mammary gland to make the lactose of milk (milk sugar). - The term galactose ia derived from Greek word gala, meaning milk. - H - C - H-C-OH - HO - C-H - H - C-OH - H-C-OH - CH2OH D-Galactose - Galactose is also an important constituent of the glycolipids that occur in the brain and the myelin sheath of nerve cells. For this reason it is also known as brain sugar. ## Ring (Cyclic) Structures - The open chain formula of sugars fails to explain some reaction. - This indicates that the -CHO group is masked or combined in some way. - In solution, the sugar which has an aldehyde group undergoes the following: ### 1- Hydration of aldehyde group to form aldenol group. - CHO Aldehyde group - CHO H-C-OH HO-C-H H-C-OH H-C-OH CH2OH Aldehyde - HO - OH CH - H-C-OH HO-C-H H-C-OH H-C-OH CH 2OH Aldenol ### 2- Intramolecular reactions occur by subsequent condensation between: - One of the -OH of aldenol group and the –OH group of C4 or C5 to form ring structure. - HO - OH CH - H-C-OH HO-C-H H-C-OH H-C-OH CH2OH Aldenol ### Cyclic Structures: If the remaining -OH ia on the right side, so it is α – sugar. If the remaining -OH is on the left side, so it is β – sugar - HO - H H-COH HO-CH H-C-OH H-C-OH CH2OH β-Glucose (1-5 ring form) - OH - H H-COH HO-CH H-C-OH H-C-OH CH2OH α-Glucose (1-5 ring form) - HO - H H-COH HO-CH H-C-OH H-C CH2OH β-Glucose (1-4 ring form) - OH - H H-COH HO-CH H-C-OH H-C CH2OH α-Glucose (1-4 ring form) ## Cyclic Structures ### Pyranose and furanose: - The 1-5 ring form is called pyranose e.g. α and β glucopyranose. - The 1-4 ring form is called furanose e.g. α and β glucofuranose. - furan - pyran ### Haworth and chair forms: - Cyclic structure of sugars may be present in the form of Haworth or chair forms. - 4. - 5 - 0 - 3 - 1 - 2 Chair form - 0 - 5 - 4 - 0 - 1 - 0 - 3 - 2 - 3 - 2 - 1 Old pyranose Haworth furnose Haworth puranose Old furnose ring form form ring form form ### Haworth Structure for D-Isomers - Write -OH groups on the right in old ring structure (C2, C4) down - Write -OH groups on the left in old ring structure (C3) up - The new-OH on C1 has two possibilities: - down for α anomer, up for β anomer - CH2OH - 0 - OH OH - OH - OH α-D-Glucose - OH - CH2OH - 0 - OH OH - OH - OH β-D-Glucose ### Forms of glucose in solutions - Glucose in solution is present mainly (99%) as glucopyranose and (1%) as glucofuranose. - Of 99% of glucopyranose (36%) are present as α – D form and (63%) a β-D form. - Glucofuranose - (1%) - α-D-glucpyranose - (36%) - β-D-glucpyranose - (63%) ### Isomerism in carbohydrates ### Asymmetric (chiral) carbon atom : - Is that carbon atom which is attached to four different groups or atoms. - Any substance containing asymmetric carbon atom shows two properties: - 1- optical activity - 2- optical isomerism. - OH - CH2 - H - OH - C - HO2HC - CHO - OHC - CH2OH ### Optical activity: - It is the ability of substance to rotate plane-polarized light either to the right or to the left. - A beam of ordinary light can be pictured as a bundle of waves; some move up and down, some sideways, and others at all other conceivable angles. - When a beam of light has been polarized, however, the waves in the bundle all vibrate in a single plane. - Light altered in this way is called plane-polarized light - Certain substances act on polarized light by rotating the plane of vibration. Such substances are said to be optically active. - (a) - (b) The light on the left is not polarized, while that on the right is polarized. - If the substance rotates plane polarized light to the right (clockwise) so it is called: dextrorotatory or d or (+). - If it rotates it to the left (counter clockwise)so it is called: levorotatory or “l” or(-). - The extent of optical activity is measured by a polarimeter. - Ordinary light (i.e. light vibrates in all directions) - Plane polarized light (i.e. light vibrates in one direction) - Plane polarized light - Solution of optically active substance - Right (Dextrorotatory: d or +) - Left (Levorotatory; I or -) ### Optical activity: - Glucose contains 4 asymmetric carbon atoms. - It is dextrorotatory, so it is sometimes named dextrose. - Fructose contains 3 asymmetric carbon atoms. - It is levorotatory so it is sometimes called Levulose. - H-C=O - * - H-C-OH - HO-C-H - * - H-C-OH - H -* - C-OH - H2-C-Oн Glucose "4 carbons labeled * with are asymmetric" - H - C - = 0 - HO-C-H - * - H-C-OH - * - H-C-OH - H2-C-Oн Fructose "3 carbons labeled with * are asymmetric Dextrose Levulose - 1 - 1 - 1 - 1 - CHO - CHO - CHO - CHO - CHO - 2 - 1 - 1 - 1 HC-OH - HCOH - H-C ‐ OH - H-C-OH - H-C-OH - 3 - HO-C-H - HO-C-H - 2 - HO-CH - HO-C-H - H ‐C ‐ OH - H-C ‐ OH - 2 - HCOH - H ‐C ‐ OH - H-C-OH - 3 - CH2‐OH - CH2‐OH - CH2‐OH - CH2‐OH - CH2‐OH - 4 - 4 - 4 - 4 - 4 ## Specific Rotation - It is the angle of rotation specific for each optically active substance when: - The concentration of substance is 100 g/dl. - The length of measuring tube is 10 cm - e.g. - Specific rotation for glucose is (+52.5°) and for fructose is (-91°). ## Racemic mixture and resolution: ### Racemic mixture: - It is the mixture containing equal number of molecules of two optically active sugars, one is dextrorotatory and the other is levorotatory. Thus, it shows no optical activity (provided that the angle of rotation is equal in both sides). ### Resolution: - It is the separation of optically inactive racemic mixture into its optically active substances. ## Optical isomerism - It is the ability of substance to present in more than one form. - A substance containing one asymmetric carbon has 2 isomers. - A substance containing 2 or more asymmetric carbon atoms can exist in a number of isomers = 2n where n is the number of asymmetric carbon atoms. - E.g. glucose has 4 asymmetric carbon atoms so the number of its isomers = 24 = 2 X 2 X 2 x 2 = 16 isomers. ## Configuration (Enantiomers or mirror image): .1 - Arrangement of –H and -OH groups around carbon atoms will result in different isomers. - The simplest carbohydrates are monosaccharides; trioses, e.g. glyceraldehyde that has one asymmetric carbon. So it has 2 optically active forms: D and its mirror image L forms. - CHO - H-C-OH - CH2OH D-Glyceraldehyde - Mirror - CHO - HO-C-H - CH2OH - L-Glyceraldehyde - CHO - D-Glyceraldehyde HC ‐ OH - CH2OH - HO-C-H - L-Glyceraldehyde - CH2OH - Enantiomers (mirror images of glyceraldehyde) - glyceraldehyde Is also called as Reference Sugar and may be present in: - (D) form in which –OH group attached to asymmetric carbon atom is on the right side - (L) form in which the same -OH group is on the left side. - All other monosaccharides are considered to be derived from the reference sugar. - H - C - H-C ‐ OH - HO ‐ C ‐ H - CH2OH - D - CH2OH - L Glyceraldehyde - They are classified into D and L forms according to the position of –OH attached to the penultimate carbon atom next to last –CH2OH e.g. carbon atom number 5 in glucose. - Most of the monosaccharides occurring in mammals are of D configuration - H2C=O H-C-OH HO-C-H H-C-OH H-C-OH CH2OH D-Ribose - CH 2OH - C=O - H-C-OH - HO ‐ C ‐ H - H-C ‐ OH - HO-C-H - CH 2OH - D-Ribulose - H2C=O H-C-OH HO-C-H H-C ‐ OH H-C-OH CH2OH L-Ribose - CH2OH - C=O - H‐C‐OH - HO‐C ‐ H - H‐C ‐ OH - HO‐C ‐ H - CH 2OH - L-Ribulose ## 2. Anomeric carbon and Anomers: Anomeric carbon: ia the asymmetric carbon atom obtained from active carbonyl group: carbon number 1 in aldoses and carbon number 2 in ketoses. Anomers: are isomers obtained from the change of position of hydroxyl group attached to the anomeric carbon e.g. α and β glucose are 2 anomers. Also α and β fructose are 2 anomers. - HO - H H-C-OH HO-C-H H-C-OH H-C-OH CH 2OH β-D (+) Glucopyranose - H - OH H-C-OH HO-C-H H-C-OH H-C-OH CH 2OH α-D (+) Glucopyranose - Anomers - Professor Dr. Sald Oraby ## Mutarotation (Latin mutare, meaning “to change"). - It is a gradual change of specific rotation of any optically active substance having free aldehyde(-CHO) or ketone (C=O) group - It is possible to obtain a sample of crystalline glucose in which all the molecules have the α structure or all have the β structure. - The α form melts at 146°C and has a specific rotation of +112°, while the β form melts at 150°C and has a specific rotation of +18.7°. - When the sample is dissolved in water, however, a mixture is soon produced containing both anomers as well as the straight-chain form, in dynamic equilibrium - α - glucose - +112. - ẞ - Glucose - +19. - At equilibrium - + 52.5. - HOCH: - 0 H OH - H/H - H - OH - HO - H - H - OH - CH2OH α-D-Glucopyranose - (+112) - HOCH2 - 0 H OH - H/H - H - OH - HO - H - H - OH - CH2OH β-D-Glucopyranose - (+19) - HOCH2 - OH - H/H - OH - CH - Acyclic (open) - aldehyde form. - H - HO - H - OH - Mutarotation of glucose ## 3. Aldose- Ketose isomerism: - Fructose has the same molecular formula as glucose but differs in structure formula. - One contains keto group (C=O) and the other contains aldehyde group (-CHO). Both are isomers. - GLUCOSE - CHO - H-C-OH - HO-C-H - H-C-OH - H-C-OH - CH2OH - Aldose and - ketose - Isomers - FRUCTOSE - CH2OH - C=O - HO-C-H - H-C-OH - H-C-OH - CH2OH ## 4. Epimeric carbon and epimers: - Epimeric carbon: is the asymmetric carbon atom other than carbon of aldehyde or ketone group e.g. carbons number 2,3 and 4 of glucose. - Epimers:. Glucose, galactose and mannose are epimers. - Glucose has 3 epimeric carbons 2, 3 and 4. - Galactose: epimer of carbon 4. - Mannose: epimer of carbon 2. - GALACTOSE - CHO - HCOH - HOCH - HO-CH - HCOH - CH2OH - C-4-epimers - - GLUCOSE - CHO - H-C-OH - HO-C-H - H-C-OH - H-C-OH - CH2OH - C-2-epimers - MANNOSE - CHO - HO-CH - HOCH - HCOH - HCOH - CH2OH # Properties of monosaccharides: ### Physical properties: - All monosaccharides are soluble in water. - All monosaccharides show the property of optical activity. - All monosaccharides can exist in α and β forms. - All monosaccharides can undergo mutarotation # Chemical properties ### 1) Oxidation: - Oxidation of sugars gives acids (Sugar acids). - **1-Aldonic acids:**by oxidation of carbonyl carbon: - e.g. glucose - → gluconic acid. - mannose to mannonic acid and galactose to galactonic acid. - **2-Uronic acids:** by oxidation last hydroxyl carbon. - e.g. glucose - → glucuronic acid. - mannose to mannuronic acid and galactose to galacturonic acid. The glucuronic acid is used by the body for conjugation with insoluble molecules to make them soluble in water for detoxification purpose and also for synthesis of hetero polysaccharides. - **3-Aldaric acids:** strong oxidation of Both first and last carbon atoms (also known as saccharic acid). - e.g. glucose → glucaric acid or glucosaccaric - mannose to mannaric acid and galactose to mucic acid. - COOH - H-C=O H-C-OH HO-C-H - H-C-OH H-C-OH CH2-OH COOH - Gluconic acid - COOH - H-C=O H-C-OH HO-C-H - H-C-OH H-C-OH COOH - Glucuronic acid - COOH - H-C-OH - HO-C-H - H ‐ C ‐ OH - H-C-OH - H-C-OH COOH Glucosaccharic - acid ### 2) Reduction: - Reduction of carbonyl group gives the corresponding alcohol - e.g. Glucose give sorbitol - Fructose gives sorbitol and mannitol - Ribose gives ribitol - Galactose gives galacticol (dulcitol). - 1 - H-C=O - CH2-OH - CH2-OH - CH2-OH - 2 - H ‐ C ‐ OH - H-C-OH - C = O - HO ‐ C ‐ H - 3 - HO‐C-H - HO‐ C ‐ H - HO-C-H - HO‐C ‐ H - 4 - H-C-OH - H-C-OH - H ‐ C ‐ OH - H-C-OH - 5 - H ‐ C ‐ OH - H-C-OH - H-C-OH - H-C-OH - 6 - CH2-OH - CH2-OH - CH2-OH - CH2-OH - D-glucose - D-sorbitol - D-fructose - D-mannitol ### 3) Reducing sugars: - Sugars containing free aldehyde or ketone group can reduce other reagents e.g. they can reduce cupric ions of Fehling's and Benedict's reagents into cuprous ions - Cupric (blue) + sugar → Cuprous (red) + oxidized sugar - Benedict’s reagent is very commonly employed to detect the presence of glucose in urine (glucosuria). It is a standard laboratory test employed to diagnose diabetes mellitus. - These tests are nonspecific for glucose, because these reagents can be reduced also by other hexoses or other reducing compounds as vitamin C. ## 4) Reactions of phosphoric and sulphuric acids: ### a)-Reaction of phosphoric acid: - It gives phosphate esters. Fructose gives fructose-6-Phosphate while glucose gives glucose-6-Phosphate and glucose -1-Phosphate. - Metabolism of sugars inside the body starts with phosphorylation. - Glu-6-P and glu-1-P are important intermediaries of glucose metabolism. - H - OH - C - OH - 1 - Reaction at C6 - OK - HOH - 7 - H-C-OH - HO-C-H - O - H-C-OH - H-C- - CH2OH - Glucose - + HO-P-O - H - OH - C - H-C-OH - HO-C-H - O - H-C-OH - H-C- - 6 - CH2O - Reaction at C1 - OH - HOH - P=0 - OH - Glucse-6-phosphate - H - OH - C - H-C-OH - HO-C-H - O - H-C ‐ OH - H-C - CH2OH - OH - P=0 - он - Glucose-1-phosphate - Professor Dr. Sald Oraby ### b)- Reaction of sulfuric acids: - This acid is a dehydrating agent, removing 3 molecules of H2O from the sugar giving a compound called furfural. - This compound can condense with a-naphthol to give a violet ring. - This is the idea of Molish's test, a general test for all carbohydrates. ## 5) Fermentation: - Fermentation is the action of bacterial or yeast enzymes on carbohydrate. - Fermentation of sugars give ethyl alcohol and CO2. - All D-monosaccharides are fermentable. - C6H12O6 → 2CH3-CH2-OH + 2 CO2 - Hexose - Ethanol - Carbon dioxide - ADP - ADP - ATP - ATP - +AA - Glucose - 2 Ethanol - 2 Pyruvate - NAD+ - NADH - CO, - NAD+ - NADH - Co - +++ - 2 Acetaldehyde ### 6) Osazone formation: - Osazones are characteristic crystals resulting from the reaction of sugars with excess phenylhydrazine when kept at boiling temperature. - All reducing sugars (i.e. having free carbonyl group) will form osazones crystals. - Osazones are insoluble. - Osazones may be used to differentiate sugars in biological fluids like urine. - Needle shaped - crystals arranged - like a broom - Glucososazone - Hedgehog or - "pincushion with - pins" or flower of - "touch-me-not-plant - Lactososazone ## Sugar derivatives ### 1) Sugar acids: - 1. Aldonic acids - 2. Uronic acid - 3. Aldaric acid or saccharic - HCO - HCOH - HOCH - HCOH - HCOH - CH2OH - Glucose - Oxidation at - carbon 6 - HCOH - HCOH - HOCH - HCOH - COOH - Glucuronic acid - Oxidation at - carbon 1 - COOH - HCOH - HOCH - HCOH - CH2OH - Gluconic acid Oxidation at carbon 1&6 - COOH - HCOH - HOCH - HCOH - COOH - Glucaric acid ### 2) Sugar alcohols - Glucose is reduced to sorbitol (glucitol). - Galactose is reduced to galacticol (dulcitol). - Mannose is reduced to mannitol. - Fructose is reduced to mannitol and sorbitol. - Ribose ia reduced to ribitol, a constituent of vitamin B2 (riboflavin) and coenzyme FAD. - Inositol (cyclitol) is derived from glucose. ### Functions of sugar alcohol 1. Sweeteners agents in candies. 2. Moisturizing agents in food and cosmetics. 3. Inositol enters in the structure of phospholipids and it acts as precursor of second messenger ( inositol triphosphate ITP). ### 3) Deoxysug

Biochemistry Carbohydrates (1-6) PDF - First Year Medicine 2024-2025

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