Carbohydrates BIOMEDICAL IMPORTANCE Carbohydrates are the most abundant

Carbohydrates

BIOMEDICAL IMPORTANCE Carbohydrates are the most abundant organic molecules in nature. The empiric formula for many of the simpler carbohydrates is (CH 2 O)n, hence the name "hydrate of carbon. " They have a wide range of functions, including: 1. providing a significant fraction of the energy in the diet of most organisms. 2. acting as a storage form of energy in the body (glycogen). 3. serving as cell membrane components that mediate some forms of intercellular communication. 4. Carbohydrates also serve as a structural component of many organisms, including the cell walls of bacteria, the exoskeleton of many insects, and the fibrous cellulose of plants. Diseases associated with carbohydrate metabolism include diabetes mellitus, galactosemia, glycogen storage diseases, and lactose intolerance

Classification of carbohydrates : Carbohydrates are classified as : 1. Monosaccharides are those sugars that contain one unit of carbogydrate and cannot be hydrolyzed into simpler carbohydrates. 2. Disaccharides are condensation products of two monosaccharide units; examples are maltose and sucrose. 3. Oligosaccharides are condensation products of three to ten monosaccharides. Most are not digested by human enzymes. 4. Polysaccharides are condensation products of more than ten monosaccharide units; examples are the starches and dextrins, which may be linear or branched polymers.

Monosaccharides can be classified according to the number of carbon atoms they contain. Examples of some monosaccharides commonly found in humans are listed in Figure 7. 1. Carbohydrates are chemically characterized as: Carbohydrates with an aldehyde as their most oxidized functional group are called aldoses. Carbohydrates with a keto group as their most oxidized functional group are called ketoses. For example, glyceraldehyde is an aldose, whereas dihydroxyacetone is a ketose. Monosaccharides can be linked by glycosidic bonds to create larger structures (Figure 7. 3).

Table 14– 1. Classification of Important Sugars Aldoses Trioses (C 3 H 6 O 3 ) Glycerose (glyceraldehyde) Ketoses Dihydroxyacetone Tetroses(C 4 H 8 O 4 ) Erythrose Erythrulose Pentoses (C 5 H 10 O 5 ) Ribose Ribulose Hexoses (C 6 H 12 O 6 ) Glucose Fructose Heptoses (C 7 H 14 O 7 ) Sedoheptulose

BIOMEDICALLY, GLUCOSE IS THE MOST IMPORTANT MONOSACCHARIDE Glucose is the major metabolic fuel of mammals and a universal fuel of the fetus. It is the precursor for synthesis of all the other carbohydrates in the body, including for storage glycogen; ribose and deoxyribose in nucleic acids; galactose in lactose of milk, in glycolipids, and in combination with protein in glycoproteins and proteoglycans. The Structure of Glucose Can Be Represented in Three Ways The straight-chain structural formula (aldohexose; Figure (A). a cyclic structure (Figure B). The six-membered ring containing one oxygen atom is actually in the form of a chair (Figure C).

Sugars Exhibit Various Forms of Isomerism Isomers& epimers Isomers are molecules that have the same molecular formula, but have a different arrangement of the atoms in space. (different structures). For example, fructose, glucose, mannose, and galactose are all isomers of each other, having the same chemical formula C 6 H 12 O 6. 1. Epimers If two monosaccharides differ in configuration around only one specific carbon atom (with the exception of the carbonyl carbon, they are defined as epimers of each other. (Of course, they are also isomers!) For example, glucose and galactose are epimers in C-4 structures differ only in the position of the -OH group at carbon 4. [Note: The carbons in sugars are numbered beginning at the end that contains the carbonyl carbon that is, the aldehyde or keto group. Glucose and mannose are C-2 epimers. However, galactose and mannose are NOT epimers—they differ in the position of -OH groups at two carbons (2 and 4) and are, therefore, defined only as isomers

2. D and L isomerism: A special type of isomerism is found in the pairs of structures that are mirror images of each other. These mirror images are called enantiomers, and the two members of the pair are designated as a D- and an L-sugar. The orientation of the —H and —OH groups around the carbon atom adjacent to the terminal primary 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. D-glucose and L-glucose are enantiomers. Most of the monosaccharides in mammals are D sugars, and the enzymes responsible for their metabolism are specific for this configuration.

3. Cyclization of monosaccharides (Pyranose and furanose) Less than one percent of each of the monosaccharides with five or more carbons exists in the open-chain (acyclic) form. Rather, they are predominantly found in a ring form, in which the aldehyde (or ketone) group has reacted with an alcohol group on the same sugar. The ring structures of monosaccharides are similar to the ring structures of either pyran (a six-membered ring) or furan (a five-membered ring) (Figures 14– 3 & 14– 4). For glucose in solution, more than 99% is in the pyranose form. Figures 14– 3 Pyranose and furanose forms of glucose.

4. Anomeric carbon (Alpha and beta anomers) : Anomeric carbon: Formation of a ring results in the creation of an anomeric carbon at carbon 1 of an aldose or at carbon 2 of a ketose. These structures are designated the α or β configuration of the sugar, for example, α -D-glucose and β -D -glucose. These two sugars are both glucose, but they are anomeric of each other. Enzymes can distinguished between these two forms: Glycogen is synthesized from α-D glucopyranose Cellulose is synthesized from β D glucopyranose Figures 14– 4

5. Optical Activity When a plane polarized light is passed through a solution containing monosaccharides the light will either be rotated towards right or left. This rotation is because of the presence of asymmetric carbon atom. If it is rotated towards left- levorotatory (-) If it is rotated towards right- dextrorotatory(+) 6. Aldose-ketose isomerism: Fructose has the same molecular formula as glucose but differs in its structural formula, since there is a potential keto group in position 2, the anomeric carbon of fructose (Figures 14– 4), whereas there is a potential aldehyde group in position 1, the anomeric carbon of glucose (Figures 14– 3).

Reducing sugars: Sugars in which the oxygen of the anomeric carbon (the carbonyl group) is free and not attached to any other structure, such sugars can act as reducing agents and are called reducing sugars A reducing sugar can react with chemical reagents (for example, Benedict's solution) and reduce the reactive component, with the anomeric carbon becoming oxidized. [Note: Only the state of the oxygen on the anomeric carbon determines if the sugar is reducing or nonreducing—the other hydroxyl groups on the molecule are not involved. ]

Many Monosaccharides Are Physiologically Important Derivatives of trioses, tetroses, and pentoses and of a seven-carbon sugar (sedoheptulose) are formed as metabolic intermediates in glycolysis and the pentose phosphate pathway. Pentoses are important in nucleotides, nucleic acids, and several coenzymes. Glucose, galactose, fructose, and mannose are physiologically the most important hexoses. In addition, carboxylic acid derivatives of glucose are important, including D -glucuronate (for glucuronide formation and in glycosaminoglycans) and its metabolic derivative, L -iduronate (in glycosaminoglycans) Deoxy Sugars Lack an Oxygen Atom Deoxy sugars are those in which one hydroxyl group has been replaced by hydrogen. An example is deoxyribosein DNA.

Sugar derivatives w sugar alcohol - lacks an aldehyde or ketone; e. g. , ribitol. w sugar acid - the aldehyde at C 1, or OH at C 6, is oxidized to a carboxylic acid; e. g. , gluconic acid, glucuronic acid.

Sugar derivatives amino sugar - an amino group substitutes for a hydroxyl. The amino sugars Are Components of Glycoproteins, Gangliosides, & Glycosaminoglycans include D -glucosamine, a constituent of hyaluronic acid , D -galactosamine, a constituent of chondroitin and D -mannosamine. The amino group may be acetylated, as in N-acetylglucosamine. Several antibiotics (eg, erythromycin) contain amino sugars, which are important for their antibiotic activity.

Sugar derivatives N-acetylneuraminate (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological p. H, as shown here.

Glycosidic Bonds Glycosides (glycosidic bond ) are formed by condensation between the hydroxyl group of the anomeric carbon of a monosaccharide, and a second compound that may or may not be another monosaccharide , splitting out water. R-OH + HO-R' R-O-R' + H 2 O If the second group is a hydroxyl, the O-glycosidic bond is an acetal link because it results from a reaction between a hemiacetal group (formed from an aldehyde) and another —OH group. If the hemiacetal portion is glucose, the resulting compound is a glucoside; if galactose, a galactoside; and so on. If the second group is an amine, an N -glycosidic bond is formed, eg, between adenine and ribose in nucleotides such as ATP.

Naming glycosidic bonds: Glycosidic bonds between sugars are named according to the numbers of the connected carbons, and also with regard to the position of the hydroxyl group of the sugar involved in the bond. If this anomeric hydroxyl group is in the α configuration, the linkage is an α-bond. If it is in the β configuration , the linkage is a β-bond. Lactose, for example, is synthesized by forming a glycosidic bond between carbon 1 of a β-galactose and carbon 4 of glucose. The linkage is, therefore , a β(1 —>4) glycosidicbond. [Note: Because the anomeric end of the glucose residue is not involved in the glycosidic linkage it (and, therefore, lactose) remains a reducing sugar. ].

Maltose, Sucrose, & Lactose Are Important Disaccharides The disaccharides are sugars composed of two monosaccharide residues linked by a glycoside bond The physiologically important disaccharides are maltose, sucrose, and lactose. Hydrolysis of sucrose yields a mixture of glucose and fructose called "invert sugar" because fructose is strongly levorotatory and changes (inverts) the weaker dextrorotatory action of sucrose.

POLYSACCHARIDES Serve storage & structural functions polysaccharides HOMO polysaccharides (all 1 type of monomer), e. g. , glycogen, starch, cellulose, chitin HETERO polysaccharides (different types of monomers), e. g. , peptidoglycans, glycosaminoglycans Polysaccharides include the following physiologically important carbohydrates: Starch is a homopolymer of glucose forming an -glucosidic chain, called a glucosan or glucan. It is the most important dietary carbohydrate in cereals, potatoes, legumes, and other vegetables.

Starch and glycogen Function: glucose storage Starch -- 2 forms: 1. amylose (13– 20%), which has a nonbranching helical structure of α(1 -> 4) linked glucose residues (Figure A). 2. amylopectin (80– 85%), which consists of branched chains of a(1 -> 4) linked glucose residues with a(1> 6) linked branches (Figure B)

Starch and glycogen Glycogen: branched polymer of a(1 -> 4) linked glucose residues with a(1 -> 6) linked branches like amylopectin but even more highly branched and more compact branches increase H 2 O-solubility

Cellulose and chitin Function: STRUCTURAL, rigidity important Cellulose: homopolymer, β(1 -> 4) linked glucose residues cell walls of plants Chitin: homopolymer, β(1 -> 4) linked N-acetylglucosamine residues hard exoskeletons (shells) of arthropods (e. g. , insects, lobsters and crabs)

Metabolism of carbohydrates The principal sites of dietary carbohydrate digestion are the mouth and intestinal lumen. This digestion is rapid and is generally completed by the time the stomach contents reach the junction of the duodenum and jejunum. A. Digestion of carbohydrates begins in the mouth The major dietary polysaccharides are of animal (glycogen) and plant origin (starch, composed of amylose and amylopectin). salivary α-amylase acts briefly on dietary starch in a random manner, breaking some a(1 -» 4) bonds. Carbohydrate digestion halts temporarily in the stomach, because the high acidity inactivates the salivary α-amylase. B. Further digestion of carbohydrates by pancreatic enzymes occurs in the small intestine When the acidic stomach contents reach the small intestine, they are neutralized by bicarbonate secreted by the pancreas, and pancreatic α-amylase continues the process of starch digestion.

Final carbohydrate digestion by enzymes synthesized by the intestinal mucosal cells The final digestive processes occur at the mucosal lining of upper jejunum. isomaltase, cleaves the bond α(1 -» 6) in isomaltose maltase cleaves maltose, both producing glucose. sucrase cleaves sucrose producing glucose and fructose. lactase (β-galactosidase) cleaves lactose producing galactose and glucose. These enzymes are secreted through, and remain associated with, the luminal side of the brush border membranes of the intestinal mucosal cells.