Carbohydrates and Metabolism - Importance of Carbohydrates - Fundamental to metabolism - Often involved in protein folding and function - Monosaccharides - Defined as aldehydes or ketones with two or more alcohol groups - Simplest carbohydrates; smallest are composed of three carbons, such as glyceraldehyde and dihydroxyacetone (DHAP) - Basic formula: $C<em>xH</em>{2x}O_x$ - Some carbohydrates contain amine groups which do not fit this formula - D versus L stereochemistry is defined by the chiral carbon farthest from the aldehyde, compared to L and D glyceraldehyde; most natural sugars have D configuration ## Isomeric Forms of Monosaccharides - Types of Isomers - Review definitions: - Isomers: Compounds with the same formula but different structures - Constitutional Isomers: Differ in connectivity - Stereoisomers: Same connectivity but different arrangement - Epimers: Differ at one specific stereocenter - Anomers: Special type of epimer formed during ring closure - Enantiomers: Non-superimposable mirror images - Diastereomers: Not mirror images and not identical ## Biological Relevance of D-Isomers - D-isomers dominate in biological systems - L-isomers are rare in nature, with few exceptions ## Ring Formation in Monosaccharides - Chemical Basis - Aldehydes react with alcohols to form hemiacetals - Ketones react with alcohols to form hemiketals - Cyclic Forms - Sugars predominantly exist as cyclic structures: - Glucose: Forms a six-carbon ring (pyranose) - Resembles pyran - Fructose: Forms a five-carbon ring (furanose) - Resembles furan ## Anomers and Their Significance - Anomeric Forms of Fructose - Formed when the hydroxyl at C-2 is oriented differently (α or β forms) - Cyclic Hemiacetals - Glucose has anomers based on stereochemistry at C-1 - α form: Hydroxyl below the ring plane - β form: Hydroxyl above the ring plane - Stability favoring cyclic forms is due to the energetics of six-membered rings ## Conformational Analysis of Pyranose Rings - Chair and Boat Conformations - Pyranose rings can exist in two types of conformations: - Chair form: Less steric hindrance - Boat form: More steric hindrance - β-D-glucopyranose primarily adopts the chair conformation due to minimized steric strain ## Oligosaccharides and Glycosidic Bonds - Formation of Glycosidic Bonds - Oligosaccharides are linked by glycosidic bonds - Catalyzed by glycosyltransferases - Monosaccharide substrates activated by nucleotide phosphates (e.g., UDP activated galactose) - Types of glycosidic bonds: - α: Non-reducing end - β: Reducing end - An O-glycosidic bond forms between the anomeric carbon and a hydroxyl group of another molecule, resulting in a glycoside ## Characteristics of Reducing and Non-Reducing Sugars - Glucose in Solution - Contains one-third α-anomer, two-thirds β-anomer, and less than 1% open chain form - Anomeric forms exist in equilibrium with an open chain form - Reducing Sugars - Sugars with aldehyde/ketone character - React with oxidizing agents - Examples include glucose and lactose - Non-Reducing Sugars - Anomeric carbon is modified and cannot revert to a linear form - Examples include sucrose and UDP-glucose ## Polysaccharides - Definition - Polysaccharides are large polymeric oligosaccharides - Homopolymers consist of only one type of monosaccharide - Glycogen - Glycogen serves as the storage form of glucose in animal cells - Composed of glucose units linked by α-1,4-glycosidic bonds; branches formed by α-1,6-glycosidic bonds every 10 glucose units - Contains approximately 30,000 glucose units per molecule - Core structure involves a homodimer of glycogenin ## Glycoproteins - Definition and Classification - Proteins with carbohydrate attachments are termed glycoproteins - Three Main Classes: 1. Glycoproteins: Protein is the largest weight component, functioning in various roles like membrane proteins 2. Proteoglycans: Consist of a protein linked to glycosaminoglycans, primarily carbohydrate, and play structural or lubricating roles 3. Mucins or Mucoproteins: Predominantly carbohydrate with specific attachment through N-acetylgalactosamine, often serving as lubricants - Example: Erythropoietin, a glycoprotein glycosylated on asparagine and serine residues - Role in Saliva - Saliva contains mucins (90% glycans, 10% protein) contributing to its slippery nature and serving as the first barrier against bacterial infections ## Attachment Sites for Carbohydrates in Glycoproteins - Linkages - Carbohydrates can attach via nitrogen atom in asparagine (N-linkage) or oxygen atom in serine/threonine (O-linkage) - N-linked polysaccharides consist of a common pentasaccharide core (three mannoses, a six-carbon sugar, and two N-acetylgalactosamine) with potential additional monosaccharides ## Human ABO Blood Groups and Glycosylation - ABO Blood Group System - Reflects specificity of glycosyltransferases - All groups share an oligosaccharide foundation called O; individuals with O-negative blood are universal donors - Transferase Actions: - A blood type has N-acetylgalactosamine added - B blood type has galactose added - AB blood types possess both and can accept from A, B, and O negative donors - Blood groups determined by glycosylation patterns on surface proteins - Importance of minor differences (e.g., N-acetyl group) in immune response and compatibility ## Lectins and Cell Interaction - Function of Glycan-Binding Proteins - Bind to specific oligosaccharides on cell surfaces - Lectins - Class of glycan-binding proteins facilitating cell-cell interaction through multiple weak interactions - Example: Influenza virus entry mechanism involves hemagglutinin, a lectin that binds to sialic acid on the cell surface - Hemagglutinin is responsible for recognizing and binding carbohydrates; the virus cleaves sialic acid through sialidase enzyme to infect new cells - Anti-Influenza Drugs - Tamiflu and Relenza inhibit the sialidase enzyme, preventing viral release from infected cells