Carbohydrates Biochemistry (BMS 233) L.Noha Soliman

Carbohydrates

Objectives After studying this chapter, you should be able to: 1- Explain what is meant by the glycome, glycobiology, and the science of glycomics. 2- Explain what is meant by the terms monosaccharide, disaccharide, oligosaccharide , and polysaccharide. 3- Explain the different ways in which the structures of glucose and other monosaccharides can be represented, and describe the various types of isomerism of sugars and the pyranose and furanose ring structures. 4- Describe the formation of glycosides and the structures of the important disaccharides and polysaccharides. 5- Describe the roles of carbohydrates in cell membranes and lipoproteins.

Biomedical Importance Glycobiology is the study of the roles of sugars in health and disease. The glycome is the entire complement of sugars of an organism, whether free or present in more complex molecules. Glycomics is the comprehensive study of glycomes.

Biomedical Importance Carbohydrates are the most abundant organic molecules in nature. They have a wide range of functions, including : Providing a significant fraction of the dietary calories for most organisms. Acting as a storage form of energy in the body. Serving as cell membrane components. Serving as a structural component of many organisms, including the cell walls of bacteria, the exoskeleton of many insects, and the fibrous cellulose of plants.

Biomedical Importance Carbohydrates composed of carbon, hydrogen, and oxygen in a 1:2:1 empirical ratio. The empiric formula for many of the simpler carbohydrates is C(H2O)n , hence the name ( hydrate of carbon). If a carbohydrate has 5 carbons atoms, what would be its empirical formula? If a carbohydrate has 12 hydrogen atoms present, what would be its empirical formula? C5H10O5 C6H12O6

Biomedical Importance Carbohydrates are widely distributed in plants and animals; they have important structural and metabolic roles. In plants , glucose is synthesized from carbon dioxide and water by photosynthesis and stored as starch or used to synthesize the cellulose of the plant cell walls. Animals can synthesize carbohydrates from amino acids, but most are derived ultimately from plants.

Carbohydrates are aldehyde or ketone derivatives of polyhydric alcohols Carbohydrates are classified as follows: Monosaccharides - single sugar unit Disaccharides - two sugar units Oligosaccharides - 3 to 10 sugar units Polysaccharides - more than 10 units

MONOSACCHARIDES ALDOSE KETOSE FUNCTIONAL GROUP NUMBER OF C ATOMS They are those sugars that cannot be hydrolyzed into simpler carbohydrates. They may be classified upon its: FUNCTIONAL GROUP ALDOSE KETOSE NUMBER OF C ATOMS TRIOSE PENTOSE HEXOSE

Monosaccharide Classification Classified by number of carbons: 3C = Trioses (C3H6O3) 4C = Tetroses (C4H8O4) 5C = Pentoses (C5H10O5) 6C = Hexoses (C6H12O6) 7C = Heptoses (C7 H14 O7) Glyceraldehyde H OH O C OH H HO CH2OH O Glucose H OH HO O Ribose CH2OH 6 5 3

Monosaccharide Classification It can be classified based on functional group (According to where the carbonyl group is located): Aldose Ketose The carbonyl group (C=O) at the first carbon position, which forms an aldehyde group (CHO). The carbonyl group (C=O) at the second carbon position, which forms a ketone group.

Monosaccharide Classification

Learning check Identify each as Aldo- or Keto- and as Triose Tetrose, Pentose, or Hexose: Aldohexose Ketopentose

Biomedically , Glucose is the most important monosaccharide Carbohydrates are chains (polymers) made of monomers. The most common monomer of carbohydrates is… GLUCOSE

Glucose is the most important carbohydrate; most dietary carbohydrate is absorbed into the bloodstream as glucose formed by hydrolysis of dietary starch and disaccharides , and other sugars are converted to glucose in the liver.

The structure of Glucose can be represented in three ways Fisher projection: straight chain form. Haworth projection: simple ring. Chair form. α- D-Glucose D-Glucose α- D-Glucose

Sugars exhibit various Forms of isomerism Sugars isomerism Sugars exhibit various Forms of isomerism

1. D and L Isomerism: (Enantiomers) Pairs of structures that are mirror images of each other and CANNOT be superimposed on each other. Designated by D- or L- at the start of the name.

1. D and L Isomerism: (Enantiomers) The designation of a sugar isomer as the D form or its mirror image as the L form is determined by its spatial relationship to the parent compound of the carbohydrates, the three-carbon sugar glycerose (glyceraldehyde).

1. D and L Isomerism: (Enantiomers) The orientation of the -H and -OH groups around the carbon atom adjacent to the terminal alcohol carbon (carbon 5 in glucose) determines whether the sugar belongs to the D or L series. When the —OH group on this carbon is on the right , the sugar is the D isomer; when it is on the left, it is the L isomer.

1. D and L Isomerism: (Enantiomers) Most of the naturally occurring monosaccharides are D sugars, and the enzymes responsible for their metabolism are specific for this configuration.

2. Pyranose and Furanose ring structures: The ring structures of monosaccharides are similar to the ring structures of either pyran (a six-membered ring) or furan (a five membered ring). For glucose in solution, more than 99% is in the pyranose form.

3. Alpha and beta anomers: The ring structure of an aldose is a hemiacetal, since it is formed by reaction between an aldehyde and an alcohol group. Similarly, the ring structure of a ketose is a hemiketal.

3. Alpha and beta anomers:

3. Alpha and beta anomers: Crystalline glucose is α-D-glucopyranose. The cyclic structure is retained in the solution, but isomerism occurs about position 1, the carbonyl or anomeric carbon atom, to give a mixture of α-glucopyranose (38%) and β-glucopyranose (62%). Less than 0.3% is represented by α and β anomers of glucofuranose.  - glucose  - glucose hydroxyl (-OH) group of the C1 projects below the plane of the ring hydroxyl (-OH) group of the C1 projects upward the plane of the ring

4. Epimers: Two sugars that differ in configuration at only one chiral center. The most important epimers of glucose are: Mannose epimerization at C2 Galactose epimerization at C4

5. Aldose – Ketose Isomerism: (Isomers) They are compounds that have the same molecular formula but have different structures. Glucose and Fructose both have the empirical formula C6H12O6 but they have different structural formulas or shapes.

Many Monosaccharides Are Physiologically Important Pentoses are important in nucleotides, nucleic acids, and several coenzymes.

Many Monosaccharides Are Physiologically Important Glucose, galactose, fructose, and mannose are physiologically the most important hexoses.

Joining of monosaccharides Monosaccharides can be joined to form disaccharides, oligosaccharides, and polysaccharides. The bonds that link sugars are called glycosidic bonds.

Naming glycosidic bonds Glycosidic bonds between sugars are named according to the numbers of the connected carbons, and with regard to the position of the anomeric hydroxyl group of the sugar involved in the bond. If this anomeric hydroxyl is in the α configuration, the linkage is an α-bond. If it is in the β configuration, the linkage is a β-bond.

Naming glycosidic bonds Lactose, for example, is synthesized by forming a glycosidic bond between carbon 1 of β-galactose and carbon 4 of glucose. The linkage is, therefore, a β(1→4) glycosidic bond.

Sugars Form Glycosides With Other Compounds & With Each Other Glycosides are formed by condensation between the hydroxyl group of the anomeric carbon of a monosaccharide, and a second compound that may be another monosaccharide or, in the case of an aglycone, not a sugar. Glycosides are widely distributed in nature; the aglycone may be methanol, glycerol, a sterol, a phenol, or a base such as adenine. The glycosides that are important in medicine because of their action on the heart (cardiac glycosides) all contain steroids as the aglycone. Other glycosides include antibiotics such as streptomycin.

Sugars Form Glycosides With Other Compounds & With Each Other Carbohydrates can be attached by glycosidic bonds to non-carbohydrate structures, including purine and pyrimidine bases (found in nucleic acids), aromatic rings (such as those found in steroids and bilirubin), proteins (found in glycoproteins and proteoglycans), and lipids (found in glycolipids).

N- and O-glycosides If the group on the non-carbohydrate molecule to which the sugar is attached is an –NH2 group, the structure is an N-glycoside and the bond is called an N-glycosidic link. If the group is an –OH, the structure is an O-glycoside, and the bond is an O-glycosidic link. Note: All sugar–sugar glycosidic bonds are O-type linkages.

Deoxy Sugars Lack an Oxygen Atom Deoxy sugars are those in which one hydroxyl group has been replaced by hydrogen. An example is deoxyribose in DNA.

Amino Sugars (Hexosamines) are Components of Glycoproteins, Gangliosides,& Glycosaminoglycans The amino sugars include D-glucosamine, a constituent of hyaluronic acid. D-galactosamine (also known as chondrosamine), a constituent of chondroitin. Several antibiotics (eg, erythromycin) contain amino sugars, which are important for their antibiotic activity.

The disaccharides are sugars composed of two monosaccharide residues linked by a glycoside bond. These are formed when two monosaccharide molecules join together with the elimination of one molecule of water. (Dehydration synthesis reaction). CH2OH H O H OH OH CH2OH H O H HO OH CH2OH H O H OH H O H O H20 + α- GLUCOSE α- GLUCOSE MALTOSE

DISACCHARIDES The physiologically important disaccharides are maltose, sucrose, and lactose.

GLUCOSE + GLUCOSE Maltose (malt sugar) GLUCOSE + FRUCTOSE Sucrose (cane sugar) GLUCOSE + GALACTOSE Lactose (milk sugar)

OLIGOSACCHARIDES Oligosaccharides are condensation products of three to ten monosaccharides. Most are not digested by human enzymes.

POLYSACCHARIDES Polysaccharides are condensation products of more than ten monosaccharide. In addition to starch and dextrin, foods contain a wide variety of other polysaccharides that are collectively known as nonstarch polysaccharides; they are not digested by human enzymes, and are the major component of dietary fiber. Examples are cellulose from plant cell walls (a glucose polymer) and inulin, the storage carbohydrate in some plants (a fructose polymer).

POLYSACCHARIDES Structural Polysaccharides Storage Polysaccharides Molecular structure determines function. The function of the polysaccharide depends on what type of isomer of glucose the polysaccharide is made. Storage Polysaccharides Energy storage - starch and glycogen. Structural Polysaccharides Used to provide protective walls to cells – cellulose and chitin. In starch In cellulose

POLYSACCHARIDES

POLYSACCHARIDES SERVE STORAGE & STRUCTURAL FUNCTIONS Polysaccharides include a number of physiologically important carbohydrates: Starch is a homopolymer of glucose forming an α-glucosidic chain, called a glucosan or glucan. It is the most important dietary carbohydrate in cereals, potatoes, legumes, and other vegetables.

STARCH The two main constituents are amylose (13%-20%), which has a nonbranching helical structure, and amylopectin (80%-87%), which consists of branched chains consists of 24 to 30 glucose residues with α1 → 4 linkages in the chains and by α1 → 6 linkages at the branch points. Dextrins are intermediates in the hydrolysis of starch.

Glycogen Glycogen is the storage polysaccharide in animals and is sometimes called animal starch. It is a more highly branched structure than amylopectin, with chains of 12 to 15 α-D glucopyranose residues (in α1 → 4 glucosidic linkage) with branching by means of α1 → 6 glucosidic bonds.

Inulin Inulin is a storage polysaccharide of fructose (a fructosan) found in tubers. It is readily soluble in water and is used to determine the glomerular filtration rate. but it is not hydrolyzed by intestinal enzymes, so has no nutritional value.

Cellulose Cellulose is the chief constituent of plant cell walls.

Cellulose It is insoluble and consists of β-D-glucopyranose units linked by β-1,4 glycosidic bonds to form long, straight chains strengthened by cross-linking hydrogen bonds. Mammals lack any enzyme that hydrolyzes the β1 → 4 bonds, and so cannot digest cellulose.

Chitin Chitin is a structural polysaccharide in the exoskeleton of crustaceans and insects, and also in mushrooms. It consists of N-acetyl-D-glucosamine units joined by β1 → 4 glycosidic bonds.

Chitin

Pectin occurs in fruits; it is a polymer of galacturonic acid linked α-1→ 4, with some galactose an/or arabinose branches, and is partially methylated.

Glycosaminoglycans They are complex carbohydrates containing amino sugars and uronic acids. They may be attached to a protein molecule to form a proteoglycan. Proteoglycans provide the ground or packing substance of connective tissue. They hold large quantities of water and occupy space, thus cushioning or lubricating other structures, because of the large number of ´OH groups and negative charges on the molecule, which, by repulsion, keep the carbohydrate chains apart. Examples are hyaluronic acid, chondroitin sulfate, and heparin.

Glycoproteins They are proteins containing branched or unbranched oligosaccharide chains , including fucose. They occur in cell membranes and many proteins are glycosylated.

CARBOHYDRATES OCCUR IN CELL MEMBRANES & IN LIPOPROTEINS Approximately 5% of the weight of cell membranes is the carbohydrate part of glycoproteins and glycolipids. Glycophorin is a major integral membrane glycoprotein of human erythrocytes. Carbohydrates are also present in apo-protein B of plasma lipoproteins.

SUMMARY The glycome is the entire complement of sugars of an organism, whether free or present in more complex molecules. Glycomics is the study of glycomes, including genetic, physiological, pathological, and other aspects. Carbohydrates are major constituents of animal food and animal tissues. They are characterized by the type and number of monosaccharide residues in their molecules. Glucose is the most important carbohydrate in mammalian biochemistry because nearly all carbohydrate in food is converted to glucose for metabolism. Sugars have large numbers of stereoisomers because they contain several asymmetric carbon atoms. The physiologically important monosaccharides include glucose, the "blood sugar," and ribose, an important constituent of nucleotides and nucleic acids.

SUMMARY The important disaccharides include maltose (glucosylglucose), an intermediate in the digestion of starch; sucrose (glucosyl-fructose), important as a dietary constituent containing fructose; and lactose (galactosyl-glucose), in milk. Starch and glycogen are storage polymers of glucose in plants and animals, respectively. Starch is the major metabolic fuel in the diet. Complex carbohydrates contain other sugar derivatives such as amino sugars, uronic acids, and sialic acids. They include proteoglycans and glycosaminoglycans, which are associated with structural elements of the tissues, and glycoproteins, which are proteins containing oligosaccharide chains; they are found in many situations including the cell membrane.