Carbohydrate Biochemistry Objectives -Recognize the features and functions of different classes of carbohydrates -Understand the concept of asymmetric carbons and other diastereoisomers, epimers and enantiomers and anomers -Recognize the structure of glucose and its relationship with other monosaccharides -Understand the different reactions of monosaccharide -Understand the nature of glycosidic bond and recognize the structure of the common disaccharides -Recognize the different types and classes of polysaccharides -Understand the basic differences between amylose and cellulose -Understand the digestion of carbohydrates process, and recognize cases of abnormal degradation of disaccharides
*Functions of Carbohydrates * Classification of CHO - Monosaccharides - aldoses and ketoses * Structure of Monosaccharides -isomers, epimers and enantiomers -cyclic structure, hemiacetal and hemiketal *Reactions of monosaccharides * Derivatives of Hexoses -amino sugars -acidic sugars -Glycosides * Disaccharides -disaccharide formation and hydrolysis -nomenclature of disaccharides -glycosides * Polysaccharides (Glycans) -homo and hetero polysaccharides -Storage polysaccharides; starch & Glycogen -Structural polysaccharides, cellulose & chitin
Biochemistry of Carbohydrate Carbohydrates (CHO) are the most abundant biomolecules in nature CHO are the photosynthesis product nco2 +H2O (CH2O)n + no2 light Originally thought to have the formula (CH2O)n. Now known that only simple monosaccharides obey this rule. Carbohydrate- polyhydroxy aldehyde or ketone or a larger molecule which can be hydrolyzed to a polyhydroxy aldehyde or ketone. Functions of Carbohydrates 1. Energy source for plants and animals 2. Source of carbon in metabolic processes 3. Storage form of energy 4. Structural elements of cells and tissues 5. Some CHO participate in recognition and adhesion between cells and mediate some forms of inter cellular communications
Monosaccharides Classes of Saccharides = single polyhydroxy aldehyde or ketone unit, (eg. 6-carbon glucose, most abundant in nature) Oligosaccharides = short chain of 2- ~20 monosaccharides joined by glycosidic bonds (eg. disaccharide sucrose = glucose-fructose) - oligosaccharides > 3 residues are usually joined to protein or lipid in glycoconjugates Polysaccharides - chains > ~ 20 to 1000 s of monosaccharides in length - linear: eg. cellulose (glucose) n or chitin (N-acetylglucosamine) n - branched: eg. glycogen & starch (glucose) - depending on the sugar residues in a polysaccharide and the linkages between them, polysaccharides can have very different biological roles
Monosaccharides - Backbone = un-branched carbon chains in which all C atoms are linked by single bonds - Colorless, crystalline, solid freely soluble in water, insoluble in organic solvents - If it has keto group as the most oxidized functional group = Ketose - If it has aldehyde group as the most oxidized functional group = aldose According to the number of carbon atoms - 3 C = triose, 4 C = tetrose, 5 C = pentose, 6 C = hexose (eg. aldo- or ketohexoses) Simplest monosaccharides are 3 carbon... Common monosaccharides are 6 carbon... Aldotriose ketotriose...
Monosaccharides have asymmetric centers - All monosaccharides (except dihydroxyacetone) have one or more asymmetric carbons - eg. glyceraldehyde: middle C is a chiral center, so molecule has 2 different optical isomers or enantiomers (= stereoisomers that are non-super imposable mirror images of one another) By convention, one enantiomer = the D isomer, the other is L, HORIZONTAL: PROJECTS OUT FROM PLANE VERTICAL: PROJECTS BEHIND PLANE Configurations of glyceraldehyde:
D and L configurations of monosaccharides - Stereoisomers of monosaccharides > 3 C divided into 2 groups: differ in the configuration about the chiral center most distant from the carbonyl C In biochemistry, we use the D-L system (similar principle to the R-S system usually used in organic, but everything is compared with glyceraldehyde - In general, a molecule with n chiral centers can have 2 n stereoisomers -OH GROUP ON RIGHT, CONFIGURATION = D -OH GROUP ON LEFT, CONFIGURATION = L IN ALDOHEXOSES, C-2, C-3, C-4, AND C-5 = CHIRAL CENTERS, SO 2 4 = 16 POSSIBLE ALDOHEXOSES: 8 D AND 8 L MIRROR 1 2 3 4 5 6 - Most of the hexoses in living organisms are D-isomers
Epimers - 2 sugars that differ only in the configuration around one carbon = epimers
Series of D-ketoses - Have 1 less chiral center than aldoses - C-4 and C-5 ketoses designated by adding ul into the name of their corresponding aldose, eg. D-ribulose = ketopentose corresponding to D-ribose
Stereochemistry The D and L designation of sugars with n > 3 are taken from the chiral carbon furthest from the carbonyl carbon. Other important terminology: Enantiomers- D- and L-sugars are enantiomers (mirror image molecules) Diastereomers- nonsuperimposable, non mirror image Epimers- differ in arrangement about one other chiral carbons. Conformational isomers:
Formation of the two cyclic forms of D-Glucose
Interconversion between anomers Anomers: Isomeric forms of monosaccharides that differ only in their configuration at the anomeric carbon. Mutarotation: The interconversion of α and β anomers of the monosaccharide - α and β anomers interconvert in solution via the linear form: = mutarotation - D-glucose solution forms an equilibrium mixture of ~ 64% β, 36% α
α-d- Mannose α -D Galactose
Reactions of Monosaccharides Reducing sugars. Reduction to polyols (Alditols). Reduction of Erythrose Erythritol Mannose Mannitol Glucose Sorbitol Oxidation into acidic sugars Oxidation the OH group at C6 -uronic acid derivative Glucose Glucuronic acid (COOH at C6) Oxidation the aldehyde group at C1 -onic acid Glucose Gluconic acid (COOH at C1) Reduction of hydroxyl group into deoxy sugars Ribose 2-deoxyribose Formation of acetals, also called glycosides Glycosidic bond- bond between a sugar and an alcohol (another sugar) or amine (a base) through an O- or N- linkage
Reducing sugars -The anomeric carbon of Glc and other sugars can be oxidized by mild oxidizing agents such as Cu 2+, providing the sugar is in its open chain form, with a free carbonyl carbon at C-1 -Sugars capable of reducing Cu 2+ are called reducing sugars -The end of a chain of sugars that has a free anomeric (C-1) carbon is called the reducing end This principle was used to detect qualitatively the presence of the reducing sugars these tests are not specific for Diabetes mellitus RED COLOR Blood glucose concentration is commonly determined by measuring the amount of H2O2
Complex carbohydrates Carbohydrate can be attached by glycosidic bond to non- carbohydrate structure through an O- or N- linkage to form complex carbohydrates -The non-carbohydrate portion is called Aglycone -The entire molecule is called Glycoside Glycosidic bond- bond between the anomeric carbon of a sugar and an alcohol (can be another sugar) or amine (a base) through an O- or N- linkage. Typical Aglycone - Purines, Pyrimrdines fo form Nucleotides - Aromatic rings (steroids) - Proteins to form glycoproteins, the polypeptide is joined to the sugar moiety via Asparagine to form N-glycoside and via serine to form O-glycosides - lipids to form and glycolipids
Complex carbohydrates N-glycoside O-glycosides
Joining of sugars via glycosidic bonds - O-glycosidic bonds are formed when the -OH group of one sugar reacts withthe anomeric carbon of the other - Reaction = formation of an acetal from a hemiacetal (eg. C- 1 of gluco pyranose) and an alcohol (-OH group on C-4 of second glucopyranose molecule)
Joining of sugars via glycosidic bonds - When an anomeric carbon participates in a glycosidic bond, it cannot exist in linear form, and can no longer act as a reducing sugar (ie. it can t reduce Cu 2+ ) - The end of a di- or polysaccharide chain with a free anomeric carbon (ie. not involved in a glycosidic bond) = the reducing end - In maltose, the configuration of the anomeric carbon in the glycosidic linkage is α - Glycosidic bonds are readily hydrolyzed by mild acid NON- REDUCING END REDUCING END a a OR b b/c MUTAROTATION
The name describes the sugar with its reducing end Glycosidic bonds are readily hydrolyzed by acids Non-reducing sugars named as Glycosides Trehalose: non-reducing sugar, a major constituents of the circulating fluid od insects
Polysaccharides: are polymers of monosaccharides units of medium to high molecular weight. Homopolysaccharides contain only a single type of monomers, as starch, glycogen, cellulose Heterpolysaccharides contain two or more different kinds monomers, as glycosaminoglycans Polysaccharides could be branched or un-branched Function: storage of energy, structural elements, animal exoskeleton and provide support +- - Important cell surface components, eg. in holding cells together in tissues - Important in molecular recognition events Polysacchs. usually don t have precisely defined molecular weights, unlike proteins
Storage polysaccharides: glycogen and starch Glycogen: polymer of α (1 4) linked glucoses with α (1 6) branches (one every 8-12 glucoses), average mol. wt. = several millions. Can be 7 % wet wt. of liver Starch: = mixture of amylose, a linear polymer of α (1 4) linked glucoses, and amylopectin, a linear polymer of α (1 4) linked glucoses with α (1 6) branches (one every 4-30 glucoses) Liver cells (hepatocytes) store glycogen equivalent to a [glucose] of 0.4 M Storage polysaccharides are essentially insoluble in the cell, so they don t raise the intracellular [glucose], which would set up a very high [glucose] gradient.
Structure of Amylose Rotation is permitted about the two C-O bonds in a glycosidic linkage: most stable conformation for α (1 4) linked glucose = curved chain of rigid chairs - Conformation of a α (1 4) )-linkages in amylose and glycogen causes polymers to assume tightly coiled helical structures that form dense granules in cells. - Molecules heavily hydrated, b/c many OH groups available to H-bond to water.
Structural polysaccharides: cellulose In β(1 4)-linked polysaccharides, each residue is rotated 180 relative to its neighbors. The intra-chain H-bonds can form between ring O and the -OH of C-3 on adjacent glucoses: Cellobiose Glc β(1 4)-Glc H-bonds also form between -OH s on residues on neighboring chains....the stabilizing network of intra-chain and inter-chain H-bonds gives straight stable fibers with great tensile strength. Extensive H-bonding within molecule results in little H-bonding to water, hence fibers have low water content
Structural polysaccharides: chitin - Polymer of β(1 4)-)-linked N-acetylglucosamine - Each residue rotated 180 relative to its neighbors - Intra-chain H-bonds can form between ring O and C-3 s -OH s on adjacent sugars (as in cellulose) - Inter-chain -NH --- O=C- H-bonds between aminoacyl groups O CH 3 O=C H- N O O CH 2 OH
The End