Chapter 3.1: Carbohydrates (Cont.) PDF

Chapter 3.1: Carbohydrates (Cont.) General Biochemistry (BCH 202) Reactions of simple sugars The reactions of sugars Amino derivatives (used to...

Chapter 3.1: Carbohydrates (Cont.) General Biochemistry (BCH 202) Reactions of simple sugars The reactions of sugars Amino derivatives (used to produce structural components) Oxidation-reduction (required for monosaccharide metabolic breakdown) Glycoside formation (linkage of monosaccharides to form oligo- and polysaccharides) Esterification, Phosphorylation (reaction with alcohol, production of phosphate esters) Reducing vs non reducing sugars The hemiacetal linkage is weak and can be dissociated to give the open form. This process makes the carbonyl group available to reduce mild oxidizing agent such as ferric (Fe+3) or cupric (Cu+2) ion and the carbonyl carbon is oxidized Glucose Gluconate to a carboxyl group plus ferrous (Fe+2) or cuprous (Cu+). → This property is the basis of Fehling’s reaction, a test for the presence of reducing Reducing vs non-reducing sugars In a chemical reaction, when the anomeric carbon has an OH group, it is considered a reducing sugar So, all monosaccharides are reducing sugars. In case of converting all the hemiacetal or hemiketal linkage to the strong acetal or ketal, the sugar loses the reducing ability and is called non reducing sugar. (fructose-glucose) Reducing vs non-reducing sugars  Oxidation of aldoses (using Fehling reagent) Glucose Gluconate The product name is made by changing the –ose ending to –onic acid (-onate) (E.g. Glucose → gluconic acid or gluconate)  Oxidation of aldoses (using Fehling reagent) Recall: Ketones do not have such reducing properties of the aldehyde group due to the lack of H attached to C=O and are not oxidized under similar conditions. BUT, fructose reduces such reagents even though it contains no aldehyde group !!!!! Oxidation of ketoses (using Fehling reagent) Reduction of fructose occurs because the reagents are basic solutions and fructose is readily isomerized to a mixture of aldoses (glucose and mannose) under basic conditions. Esterification The most important biological esters of carbohydrates are P esters Esterification-Phosphorylation The addition of phosphoryl groups is common in sugar metabolism. Phosphorylation makes sugars anionic, negative charge prevents sugars from spontaneously leaving the cell by crossing lipid-bilayer membranes. Amino derivatives The replacement of a hydroxyl group on a carbohydrate with amino group results in an amino sugar: Structural components of bacteria; cell wall A component of chitin, the carbohydrate polymer forming the exoskeleton of insects A major structural unit of chondroitin sulphate, a component of cartilage of vertebrates. A component of glycoproteins and glycolipids Amino derivatives (Cont.) The amino group of glucosamine may be acetylated, as in N-acetylglucosamine. N-acetylneuraminate (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 pH Glycoside formation There are many types of glycosidic bond It is formed between the anomeric carbon of a carbohydrate and the oxygen, nitrogen or phosphorous of other compound The anomeric carbon involved in bond formation is stabilized and the bond converts to acetal or ketal (strong bond) with no potentially free aldehyde or keto groups.  Glycosylation Reaction There are several types of glycosylation, although the first two are the most common. In N-glycosylation, sugars are attached to nitrogen, typically on the amide side-chain of asparagine. In O-glycosylation, sugars are attached to oxygen, typically on serine or threonine but also on non-canonical amino acids such as hydroxylysine & hydroxyproline. Also bond between monosaccharides to form oligosaccharides and polysaccharides is o-glycosylation. Glycosylation Reaction There are several types of glycosylation, although the first two are the most common. In glypiation, is the covalent bond of Glycosyl Phosphatidylinositol (GPI) anchor and is a common post-translational modification that localizes proteins to cell membranes. Glycolipid is attached to the C-terminus of a polypeptide, serving as a membrane anchor.  Glycosylation Reaction There are several types of glycosylation, although the first two are the most common. In C-glycosylation, sugars are attached directly to carbon, such as in the addition of mannose to tryptophan. In P-glycosylation, sugars are attached to phosphorus on a phosphoserine. N-linked glycosylation Sugar molecules can be attached to asparagine or glutamine by N-linked glycosylation N-linked oligosaccharides of glycoproteins tend to be complex and branched. First N-acetylglucosamine is linked to a protein via the side-chain N of an asparagine residue in a particular 3-amino acid sequence (-Asn-X-Ser/Thr). N-linked glycosylation Additional monosaccharides are added, and the N-linked oligosaccharide chain is modified by removal and addition of residues, to yield a characteristic branched structure O-linked glycosylation Oligosaccharides can bind to a protein via O-glycosidic bond between the sugar residue & the serine or threonine OH to form linear or branched chains. ○ N-acetylglucosamine (GlcNAc) Many cellular proteins, including enzymes & transcription factors, are regulated by reversible GlcNAc attachment. Often attachment of GlcNAc to a protein OH alternates with phosphorylation, with these 2 modifications having opposite regulatory effects (stimulation or inhibition). O-linked versus N-linked glycosidic bond (a) O-linked oligosaccharides have a glycosidic bond to the hydroxyl group of Ser or Thr residues (shaded pink), illustrated here with GalNAc as the sugar at the reducing end of the oligosaccharide. Simple chain Complex chain O-linked versus N-linked glycosidic bond (b) N-linked oligosaccharides have an N-glycosyl bond to the amide nitrogen of an Asn residue (shaded green), illustrated here with GlcNAc as the terminal sugar. 3 common types of oligosaccharide chains that are N-linked in glycoproteins  Glucose in the blood and the glycated hemoglobin In diabetic patients, the glycated hemoglobin is higher. Blood glucose reacts with the N-terminal of the beta chain of the hemoglobin nonenzymaticaly. This glycosylation reaction forms a Schiff base which is itself converted to 1-deoxy fructose. Sugar derivatives Sugar acid - the aldehyde at C1, or OH at C6, is oxidized to a carboxylic acid; e.g., gluconic acid, glucuronic acid. Sugar alcohol - lacks an aldehyde or ketone; e.g., ribitol. Disaccharides Contain a Glycosidic Bond Glycosidic bonds are readily hydrolyzed by acid but resist cleavage by base → Thus, disaccharides can be hydrolyzed to yield their free monosaccharide components by boiling with dilute acid.  Disaccharides Three types of fructose glucose Galactose* monosaccharides… …join together by an O-glycosidic bond to make three types of disaccharides sucrose maltose lactose (fructose-glucose) (glucose-glucose) (glucose-galactose) Maltose It is also called maltobiose or malt sugar. The disaccharide maltose contains two D-glucose residues joined by a O-glycosidic linkage between C-1 (the anomeric carbon) of one glucose residue and C-4 of the other. Non-reducing reducing Maltose Because the disaccharide retains ONE free anomeric carbon maltose is a reducing sugar. The configuration of the anomeric carbon atom in the glycosidic linkage is α-(1→ 4). The glucose residue with the free anomeric carbon is Non-reducing reducing capable of existing in α- and β–pyranose forms. Isomaltose Two units of glucose bound by α-1→ 6 glycosidic bond. Because the disaccharide retains ONE free anomeric carbon isomaltose is a reducing sugar. It is produced by the hydrolysis of glycogen or amylopectin. Lactose It is also called milk sugar. It is composed of galactose and glucose linked by is β-(1→ 4) glycosidic bond. So, galactose lose its reducing ability because the hemiacetal is converted to acetal bond, while the anomeric carbon of the glucose residue is available for oxidation and retains its reducing potential. →Thus lactose is a reducing disaccharide. Its abbreviated name is Gal(1→ 4)Glc.  Sucrose Sucrose (table sugar or cane sugar) is a disaccharide of glucose and fructose. It is formed by plants but not by animals. In contrast to maltose and lactose, sucrose contains no free anomeric carbon atom; The anomeric carbons of both monosaccharide units are involved in the glycosidic bond (α, β 1→ 2). ○ Sucrose is therefore a non-reducing sugar. The full name of sucrose Sucrose The hydrolysis of sucrose by acid makes the following changes: ○ It gives glucose and fructose → So, it is more sweaty, ○ It changes from non-reducing to reducing, ○ It is called invert sugar ??? Fructose is dextrorotatory. After hydrolysis, it is inverted from being dextro to levorotatory Cellobiose Two units of glucose bound by β-1→ 4 glycosidic bond Is a reducing sugar Is produced by the hydrolysis of cellulose