Mono and Oligosaccharides Fall 2023-2024 PDF

Mono- and Oligosaccharides Biochemistry (Lippincott) Chapter 7 Mark’s Basic Medical Biochemistry Chapter 5 Textbook of Medical Biochemistry Chapter 3 Fall 2023/2024 What are the diseases related to Carbohydrates?  Fructosemia (fructose intolerance) Fructosuria (inade...

Mono- and Oligosaccharides Biochemistry (Lippincott) Chapter 7 Mark’s Basic Medical Biochemistry Chapter 5 Textbook of Medical Biochemistry Chapter 3 Fall 2023/2024 What are the diseases related to Carbohydrates?  Fructosemia (fructose intolerance) Fructosuria (inadequate metabolism of fructose) Galactosemia (inability to fully break down galactose) Pentosuria (inborn error of carbohydrate metabolism) Metabolic diseases (diabetes, Gaucher's disease, and hemochromatosis..) Glycogen storage diseases (improper storage of glycogen in the body) Carbohydrates The most abundant organic molecules in nature Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis Many, but not all, carbohydrates have the empirical formula (CH2O)n; some also contain nitrogen, phosphorus, or sulfur  Functions of Carbohydrates ① – Energy source (glucose) ①– Energy storage (glycogen, starch) ③ – Structure/Protection (chitin, cellulose, connective tissue) ④ – Recognition/Signaling (Antibodies used for immune system recognition) ③– Can be attached to other macromolecules (glycoproteins and glycolipids) Classes of Carbohydrates Carbohydrates are divided into four major groups:  Monosaccharides: also called ‘simple’ sugars; are those which cannot be hydrolysed further into simpler forms, e.g. Glucose  Disaccharides: Those sugars which yield two molecules of the same or different molecules of monosaccharide on hydrolysis, e.g. Sucrose  Oligosaccharides: Those sugars which yield 3 to 10 monosaccharide units on hydrolysis, e.g. Maltotriose.  Polysaccharides: Those sugars which yield more than ten molecules of monosaccharides on hydrolysis, e.g. Starch, Glycogen..  Monosaccharides Simple monosaccharides consist of a linear chain of three or more carbon atoms, one of which forms a carbonyl group through a double bond with oxygen. The other carbons of an unmodified monosaccharide contain hydroxyl groups, resulting in the general formula for an unmodified sugar of CnH2nOn The suffix “-ose” is used in the names of sugars. Classification  According to the number of carbon atoms they contain. Examples of some monosaccharides commonly found in humans are listed below.  According to the type of carbonyl group they contain - If the carbonyl group is an aldehyde, the sugar is an aldose; if the carbonyl group is a ketone, the sugar is a ketose. Aldose Aldehyde  Combining these terms describes the essential structure of sugars For example: - Glyceraldehyde is an aldotriose - Dihydroxyacetone is a ketotriose So.. - Glucose is an aldohexose - Fructose is a ketohexose Triose Models Pentose Models Hexose Models The simplest ALDOSE is GLYCERALDEHYDE Contains an ALDEHYDE (yellow) Contains a CHIRAL center: - Carbon with 4 different groups bonded to it Called the D and L forms Almost ALL sugars are D The simplest KETOSE is DIHYDROXYACETONE Contains a KETONE Does NOT contain a chiral center The only monosaccharide that DOES NOT have a chiral center Every other monosaccharide has at least one  Medical Break Fructose Increase of fructose uptake (sweeteners): I - Development of obesity, diabetes and dyslipidemia in rodent 2 (168611 25 - Increased plasma triglyceride concentrations = is found but does not work) 3 - Hepatic insulin resistance (Insulin Y - Increased total and visceral fat mass - - E - Accumulation of ectopic fat in the liver and skeletal muscle destroy liver  Carbohydrates can also be classified by the positions of the hydroxyl groups on their asymmetric carbon atoms (D- or L-sugars (enantiomers), stereoisomers, or epimers). - Left right. ↓ or - Terms Isomers = same chemical formula, different structure Epimers = isomers that differ at only one Carbon Enantiomers = isomers that are mirror images (D and L) Anomers = isomers that differ only at keto-/aldo carbon Ianomeric Carbon) Isomers and Epimers Isomers : Compounds that have the same chemical formula but have different structures Epimers: Carbohydrate isomers that differ in configuration around only one specific carbon atom Epimers Enantiomers; D- and L-SUGARS A carbon atom that contains four different chemical groups forms an asymmetric (or chiral) center Monosaccharide stereoisomers are designated D or L based on whether the position of the hydroxyl group farthest from the carbonyl carbon matches D- or L-glyceraldehyde Mostly D Chirality Cyclization of Monosaccharides Ring Structures Monosaccharides exist in solution mainly as ring structures In the actual three-dimensional structure, the ring is not planar but usually takes a “chair” conformation in which the hydroxyl groups are located at a maximal distance from each other Mutarotation of Glucose in Solution When the ring closes, the hydroxyl group may be in either α or β position. This process occurs more rapidly in the presence of cellular enzymes called mutarotases. Mutarotation = interconversion between the and anomers  Less than 1% of each of the monosaccharides with five or more carbons exists in the open-chain (acyclic) form Predominantly found in a ring (cyclic) form Aldehyde (or keto) group has reacted with a hydroxyl group on the same sugar Modified Fischer projection formulas Haworth projection formula Pyranose refers to a six-membered and furanose denotes a five-membered Reducing Sugar The sugar that is capable of acting as a reducing agent Causing the reagent to be reduced and colored If the hydroxyl group on the anomeric carbon of cyclized sugar is not linked to another compound by a glycosidic bond, the ring can open Basis of Fehling’s Reaction = Glucose is Reducing Glucose oxidase Test Sugar Derivatives (Modified Monosaccharides)  Monosaccharides can also can be categorized according to their substituents (e.g., amino sugars) Sugars frequently contain phosphate groups, amino groups, sulfate groups, or N-acetyl groups. Most of the free monosaccharides within cells are phosphorylated Modified Sugars Medical Break Sialic acid storage disease is an inherited disorder that primarily affects the nervous sytem Salla disease; Infantile free sialic acid storage disease (ISSD) : - Severe developmental delay - Weak muscle Failure to gain weight and grow at the expected rate - Unusual facial features that are often described as "coarse," seizures, bone malformations - Enlarged liver and spleen (hepatosplenomegaly), and an enlarged heart (cardiomegaly). Caused by a mutation in a gene results in the dysfunction of a specialized protein known as sialin Monosaccharide Joining Monosaccharides can be linked by glycosidic bonds to create larger structures:  Disaccharides: 2 monosaccharide units  Oligosaccharides: 3-10 monosaccharide units  Polysaccharides: ≥ monosaccharide units (can be hundreds of sugar units) Disaccharides Important Things to Consider When Looking at a Disaccharide: 1. What are the two monosaccharides? 2. What anomer made the glycosidic bond? 3. What is the reducing sugar? Disaccharides: - Formed between monosaccharides via a glycosidic bond - Involves OH of anomeric carbon and any other OH - In the reaction, lose elements of H2O - α (1 4) - α = alpha = configuration of anomeric carbon - 1 = number of anomeric carbon - 4 = denotes other carbon involved in glycosidic bond - Anomeric carbon gets fixed/locked into either α or β configuration (can’t mutarotate) - Having lots of variation in monosaccharides and variation in how they are linked leads to many different disaccharides Biomedical Importance of Disaccharides Various food preparations, such as baby and invalid foods available, are produced by hydrolysis of grains and contain large amounts of maltose. From nutritional point of view they are thus easily digestible. In lactating mammary gland, the lactose is synthesized from glucose by the duct epithelium and lactose present in breast milk is a good source of energy for the newborn baby. Lactose is fermented by ‘Coliform’ bacilli (E. coli) which is usually non-pathogenic (lactose fermenter) and not by Typhoid bacillus which is pathogenic (lactose nonfermenter). Formation of Glycosidic Bond: Written from Non-Reducing to Reducing End Glycosides N- AND O-GLYCOSIDIC BONDS The hydroxyl group on the anomeric carbon of a monosaccharide can react with another compound to form a glycosidic bond. N-glycosidic bonds are found in nucleosides and nucleotides.  Cellobiose 1st glucose is "-linked to the 4th carbon of another glucose [glucose (14) glucose] points up so draw the bond as curved or wavy line – Up from C1 and down from C4 Lactose Galactose in a  (14) linkage with glucose Galactose is converted by the body to glucose and glucose used for energy Lactose is digestible by most humans It’s not so sweet; Found in dairy products (milk sugar) Enzyme LACTASE present in small intestine hydrolyzes lactose to galactose and glucose Lactose Intolerance - 5% of people from Scandinavia and 90% of Asian adults suffer from lactose intolerance – deficiency in enzyme lactase. - For those with the deficiency: o Lactose accumulates in small intestine o Degraded by intestinal bacteria producing CO2, hydrogen gas, and organic acids o Presence of excess undigested lactose is harmful as well o Both cause symptoms: Bloating, Nausea, Cramping, Diarrhea - Treatment:  Avoid products containing lactose (dairy products)  Use commercial products to hydrolyze lactose before consumption [Add enzyme called b-galactosidase (e.g. lactaid milk)] - Caused by Lactase deficiency and lactose malabsorption  Primary lactase deficiency: lactase production declines over time  Secondary lactase deficiency results from injury to the small intestine Infection, diseases, or other problems may injure the small intestine  Developmental lactase deficiency may occur in infants born prematurely. This condition usually lasts for only a short time after they are born.  Congenital lactase deficiency is an extremely rare disorder in which the small intestine produces little or no lactase enzyme from birth. Genes inherited from parents cause this disorder. Maltose In the body, dietary starch digestion by Amylase in gut yields maltose, which requires a specific enzyme maltase to form glucose. Malt sugar On hydrolysis Maltose yields two molecules of glucose. Sucrose f & Glucose in , (12) linkage with fructose (50% glucose:50% fructose) Anomeric carbon (C1) on glucose is linked to the anomeric carbon (C2) on fructose. BOTH anomeric carbons are involved in glycosidic bonds. Therefore, sucrose is NOT a reducing sugar  It’s very sweet; Commonly known as “table sugar” One of the principal sugars naturally occurring in fruits and honey Also produced commercially from sugar cane and sugar beet through a refinement process The specific enzyme which hydrolyses sucrose is sucrase present in intestinal juice. Oligosaccharides  Carbohydrates that contain 3-10 Monosaccharide unit Higher order oligosaccharides are named tri-, tetra-, penta-, etc. Structures may be predominately linear or branched - Biomedical Importance: IV. IN Many secreted proteins, such as antibodies and coagulation factors contain oligosaccharide units and toge ⑫ Structural Features Linear – Features a head-to-tail linkage – 1 reducing end – 1 non-reducing end Branched – 1 reducing end – Several to many non-reducing ends