Carbohydrates - Week 3 Lecture Notes

Carbohydrates Stephanie Mae K. N. Sor, RMT, MD Objectives To have an introduction to carbohydrates To be able to learn and utilize the Fischer Projection & Haworth Projection To familiarize ourselves with the chirality and the different types of isomerism encountered To learn about the...

Carbohydrates Stephanie Mae K. N. Sor, RMT, MD Objectives To have an introduction to carbohydrates To be able to learn and utilize the Fischer Projection & Haworth Projection To familiarize ourselves with the chirality and the different types of isomerism encountered To learn about the different, mono-, di-, and polysaccharides that are biochemically important Carbohydrates most abundant class of bioorganic molecules on planet Earth Green (chlorophyll-containing) plants produce carbohydrates via photosynthesis. CHO in plants § Cellulose – structural elements § Starch – energy reserve In humans, carbohydrates are obtained from the DIETARY INTAKE OF PLANT MATERIALS Functions of Carbohydrates in Humans Oxidation → provides energy. Storage → short term energy reserve in the form of glycogen C atom source – for synthesis of other biologic substances DNA and RNA structural component – ribose & deoxyribose Cell membrane component - glycolipids Cell-cell and Cell-Molecule recognition processes - glycoprotein Carbohydrates largest source of dietary calories for most of the world’s population Cn(H2O)n “hydrates of carbon” A polyhydroxyaldehyde, a polyhydroxyketone, or a compound that yields polyhydroxyaldehydes or polyhydroxyketones upon hydrolysis Carbohydrates can be classified according to molecular size or number of sugar units § Monosaccharides § Oligosaccharides § Disaccharides § Polysaccharides MONOsaccharide DIsaccharide OLIGOsaccharide POLYsaccharide A carbohydrate that 2 monosaccharides 3-10 MANY contains a single covalently bonded monosaccharides monosaccharides polyhydroxy to each other covalently bonded covalently bonded aldehyde or Produces to each other to each other polyhydroxy ketone monosaccharides Produces Produces unit or upon hydrolysis monosaccharides monosaccharides Cannot be broken Water-soluble upon hydrolysis upon hydrolysis down into simpler Crystalline Mostly not digested Examples units by hydrolysis by human enzymes Glycogen Usually contains 3-7 Examples Examples Cellulose carbon atoms Raffinose Starch Water-soluble Stachyose Crystalline solids Examples Glucose Galactose Fructose Monosaccharides Monosaccharides name ends in –ose § except: Glyceraldehyde & Dihydroxyacetone can be classified based on § number of carbons v Triose v Tetrose v Pentose v Hexose § functional group v Aldose v Ketose  E X E R C I S E Classification based on functional group Classification based on number of Carbon atoms Combination  E X E R C I S E Classification based on functional group Aldose Aldose Aldose Ketose Aldose classification based on number of Carbon atoms Triose Tetrose Pentose Hexose Hexose Combination Aldotriose Aldotetrose Aldopentose Ketohexose Aldohexose Monosaccharides Stereoisomerism Isomers have the same molecular and structural formulas but differ in orientation of atoms in space The left and right-handed forms of a chiral molecule are isomers Constitutional Isomers: Stereoisomers: Same structural formula, different connectivity Same connectivity, different arrangement in space Stereoisomerism Features that generate stereoisomerism 1. Presence of a chiral center 2. Presence of structural rigidity in a molecule Enantiomers – nonsuperimposable mirror images e.g. left- and right-handed forms of a molecule Diastereomers – not mirror images of each others Monosaccharides Handedness in Molecules Type of isomerism founds in carbohydrates § Superimposable § Non-superimposable Chirality Chiral Center – C atom bonded to 4 different groups A molecule with a chiral center is considered a chiral molecule The mirror image of chiral molecules are NOT superimposable Chirality Determining the Presence / Lack of Chiral Centers 1. If the atom is involved in a multiple bond, it is NOT a chiral center 2. If the atom written as –CH3 or –CH2– in its condensed structural formula then it is NOT a chiral center 3. Carbons in a ring system can be chiral provided they are not involved in multiple bonding Both the substituents are different The 2 halves of the ring emanating from the chiral center are different Chirality E X E R C I S E The Importance of Chirality Right-handed and left-handed forms of a molecule usually elicit different responses a. Only one is biologically active b. Each form giving a different response c. Both forms elicit the same response but one form’s response is many times greater than the other. All proteins, most fats, and all common carbohydrates are chiral Monosaccharides are almost always right-handed Amino acids are always left-handed Fischer Projection 2D notation for showing the spatial arrangement of groups about chiral centers in molecules Chiral center is represented as the intersection of vertical and horizontal lines 1. The chiral center is considered to be on the plane of this page 2. Vertical lines represent bonds going into the page 3. Horizontal lines represent bonds directed out of the page Fischer Projection D and L is sometimes used to designate handedness § D stands for Dextro – right § L stands for Levo - left glyceraldehyde (2,3-dihydroxypropanal) Conventions in drawing a Fischer Projection The chiral center is considered to be on the plane of this page Vertical lines represent bonds going into the page Horizontal lines represent bonds directed out of the page Fischer Projection in Monosaccharides The carbon chain is positioned VERTICALLY with the carbonyl group (aldehyde or ketone) at or near the top The handedness is determined using the HIGHEST NUMBERED chiral center – the chiral center farthest from the carbonyl group D isomer L isomer D isomer L isomer 1 1 1 1 2,3,4-trihydroxybutanal 2 2 2 2 3 3 3 3 4 4 4 4 D dextro (right) L levo (left) E X E R C I S E E X E R C I S E E X E R C I S E Constitutional Isomers & Stereoisomers differ in most chemical and physical properties (e.g. different boiling and melting points) Have nearly the same properties except for 2 things: interaction with plane polarized light interaction with differ in most chemical and physical properties other chiral (e.g. different boiling and freezing points) substances Interaction with Plane Polarized Light Enantiomers are OPTICALLY ACTIVE – it rotates the plane of polarized light If it rotates the plane polarized light towards the RIGHT (clockwise) → + DEXTROROTATORY If it rotates the plane polarized light towards the LEFT (counter clockwise) → - LEVOROTATORY Handedness (D & L) of enantiomers & the direction of light rotation are NOT connected entities Interaction Between Chiral Compounds The two members of an enantiomeric pair have the SAME boiling points, melting points, & densities The two members of an enantiomeric pair have the SAME interaction with ACHIRAL molecules The two members of an enantiomeric pair have DIFFERENT interactions with CHIRAL molecules Generate different responses within the human body due to chirality associated with receptor sites Cyclic/Hemiacetal Form Exist in monosaccharides containing ≥ 5 carbons Dominant form of monosaccharides at equilibrium Intramolecular reaction of the carbonyl group (–C=O) with a hydroxyl group (–OH) resulting in cyclic hemiacetals Cyclic forms of other Monosaccharides PYRANOSE FURANOSE Name due to its resemblance to the Name due to its resemblance to the cyclic ether Pyran cyclic ether Furan Cyclic monosacchoride containing a Cyclic monosacchoride containing a 6-atom ring 5-atom ring Haworth Projection 2D structural notation that specifies the 3D structure of the cyclic form of a monosaccharide hemiacetal ring system viewed “edge on” with the –O– ring atom at the § upper right (6 membered ring) or § top (5-membered ring) Position of the –CH2OH group on C5 § D form – above the ring § L form – below the ring Position of the –OH group on C1 relative to –CH2OH § ⍺ – opposite direction § β – same direction Haworth Projection The specific identity of a monosaccharide is determined by the positioning of other OH groups –OH group attached to chiral centers on Fischer Projection § Right → points DOWN in Haworth projection § Left → points UP in Haworth projection UP UP DOWN DOWN  Reactions of Monosaccharides Oxidation to Produce Acidic Sugars Oxidation can yield 3 different types depending on the oxidizing agent Weak Oxidizing Agents Strong Oxidizing Agents Enzymes yield ALDONIC acid yield ALDARIC acid yield ALDURONIC acid Reduction to Produce Sugar Alcohols Carbonyl group(–C=O) in a monosaccharide is reduced to form a hydroxyl group (–OH) Hydrogen is used as the reducing agent Yields polyhydroxy alcohols referred to as ALDITOLS Phosphate Ester Formation Hydroxyl groups (–OH) can react with inorganic oxyacids to form inorganic esters Specific enzymes in the body can catalyze the esterification of the hemiacetal group (C1) and the primary alcohol group C6 to produce PHOSPHATE ESTERS that play important roles in carbohydrate metabolism Amino Sugar Formation Hydroxyl group (–OH) of a monosaccharide is replaced with an amino group (NH2) In naturally occurring amino sugars, NH2 replaces the C2 –OH group Amino sugars and their N-acetyl derivatives are building blocks of glycosaminoglycans such as hyaluronic acid Glycoside Formation Fact: the cyclic form of monosaccharides are hemiacetals Hemiacetals are able to react with alcohols to form ACETALS Hemiacetal carbon –OH group is replaced with an –OR group The general name of monosaccharide acetals is GLYCOSIDE ( e.g. Glucose → Glucoside, Galactose → Galactoside) Exist in both ⍺ and β forms Biochemically Important Monosaccharides GLUCOSE (grape sugar) GALACTOSE (brain sugar) Most abundant in nature Seldom encountered as a Nutritionally the free monosaccharide most important Synthesized in the Used by cells as the mammary glands for use in primary source of energy lactose (milk sugar) Component of glycoproteins also known as found in nervous tissue § Dextrose – optically active Also present in the chemical markers § Blood sugar – blood contains that distinguish various blood types dissolved glucose § Insulin - ↓ glucose level § Glucagon - ↑ glucose level Biochemically Important Monosaccharides FRUCTOSE (fruit sugar) RIBOSE Most important Pentose ketohexose Important component of Sweetest-tasting of RNA and energy-rich all sugars compounds Sometimes as a dietary sugar because it requires a smaller amount to reach the same amount of DEOXYRIBOSE sweetness Important component of DNA molecules also known as lacks an Oxygen atom at § Levulose – the 2nd carbon compared to optically active ribose Disaccharides Disaccharide Formation Hemiacetal –OH atom on one monosaccharide is bonded to the –OH atom on the other monosaccharide One of the reactants function as a hemiacetal, the other functions as an alcohol to form a glycoside 2 monosaccharides are linked together by a glycosidic linkage Maltose Malt sugar Produced by the breakdown of the polysaccharide starch Common ingredient in baby foods and malted milk 1 glucose + 1 glucose linked by an ⍺(1→4) linkage Can be broken down by the enzyme maltase Lactose Milk sugar Synthesized by mammalian mammary glands by in a 4 step process Common ingredient in commercially-produced infant formula 1 glucose + 1 lactose linked by a β(1→4) linkage Can be broken down by the enzyme lactase Sucrose Table sugar Most abundant disaccharide Commercially produced from sugar cane and sugar beets 1 glucose + 1 fructose linked by a β(1→2) linkage Can be broken down by the enzyme sucrase NONREDUCING Polysaccharides Polysaccharide Also referred to as Glycans Polymer that contains many monosaccharide units bonded to each other by glycosidic linkages Not sweet, not positive for Tollen’s or Benedict’s Test Limited water solubility - –OH groups can individually become hydrated, resulting in thick colloidal suspensions of polysaccharides § Used as thickening agents in sauces, desserts, and gravy Distinguishing Parameters of Polysaccharides 1. The identity of repeating monosaccharide units § Homopolysaccharides – only 1 type of monosaccharide § Heteropolysaccharide – two or more types of monosaccharide 2. Length of the polymer chain 3. Type of glycosidic linkage between monomer units 4. Degree of branching between monomer units Storage Polysaccharides STARCH GLYCOGEN Energy storage homopolysaccharide Energy storage homopolysaccharide found in PLANTS found in ANIMALS & HUMANS Composed solely of glucose units Composed solely of glucose units Amylose – unbranched (15-20%) Stored in the liver and muscle bonds: ⍺(1→4) Bonds: ⍺(1→4) MM: 50,000 (up to 1k glucose units) ⍺(1→6) at branch points Amylopectin – branched (80-85%) MM: 3,000,000 (up to 1M glucose units) bonds: ⍺(1→4) ⍺(1→6) at branch points every 25-30 units MM: 300,000 (up to 100k glucose units) Hydrolyzed by enzymes of the human digestive tract Structural Polysaccharides CELLULOSE CHITIN Structural homopolysaccharide found Structural homopolysaccharide found in PLANT CELL WALL in ARTHROPODS & FUNGI Monomer: glucose Monomer: N-acetyl-D-glucosamine Bonds: β(1→4) Bonds: β (1→4) Most abundant polysaccharide 2nd most abundant polysaccharide NOT hydrolyzed by enzymes in the NOT hydrolyzed by enzymes in the human digestive tract human digestive tract Serves as dietary fiber – readily absorbs water leading to softer stools Acidic Polysaccharides (Glycosaminoglycans) HYALURONIC ACID HEPARIN Alternating residues of Alternating residues of N-acetylglucosamine and Sulfated iduronic acid and D-glucuronic acid Sulfated glucosamine Bonds: β(1→3) alternating with Blood anticoagulant naturally β(1→4) present in mast cells & is released at 50,000 disaccharide units/chain the site of tissue injury Found as lubricant fluid of joints and Used therapeutically to inhibit in the vitreous humor of the eye coagulation of blood Glycolipids Glycoproteins lipid molecule that has ≥ 1 protein molecule that has ≥ 1 carbohydrate (or derivative) units carbohydrate (or derivative) units covalently bonded to it covalently bonded to it Functions Functions Cerebrosides & Gangliosides – Immunoglobulins found extensively in neural tissue Cell surface recognition and Essential cell membrane antigenicity component Lubricant and protective agent in the gastrointestinal and urogenital tracts Dietary Considerations and Carbohydrates Foods high in CHO constitute over 50% of the diet of most people of the world – a balanced diet should have 60% CHO § Rice in Asia § Potato & Wheat in North America § Corn in South America § Starchy root vegetables Simple carbs – mono or disaccharides (sugars) - sweet Complex carbs –polysaccharides – not sweet Natural sugar – naturally present in whole foods such as milk and fruit; accompanied by nutrients Refined sugar – separated from its plant source (usually beet, cane); considered as empty calories References Kennelly, P. J., Botham, K. M., McGuinness, O., Rodwell, V. W., & Weil, P. A. (2022). Harper’s Illustrated Biochemistry, Thirty-Second Edition. McGraw-Hill Education / Medical. Lieberman, M., & Peet, A. (2017). Marks’ Basic Medical Biochemistry: A Clinical Approach. LWW. Nelson, D. L. (2016). Principles of Biochemistry 7e. Stoker, H. S. (2015). General, organic, and biological chemistry. Cengage Learning.