Carbohydrates Three Major Classes of Carbohydrates Monosaccharides o Simple sugars such as glucose Oligosaccharides o Short chains of monosaccharides (2-10) o Disaccharides are the most abundant o e.g., sucrose (glucose and fructose) Polysaccharides o Polymers of simple monosaccharides • • • Monosaccharides Aldose has carbonyl group at end of chain Ketose has carbonyl group internal to chain Typically cyclic in solution o Cyclization occurs between the carbonyl carbon and an OH group of another carbon in the chain o The former carbonyl carbon is now termed the anomeric carbon General formulation (CH2O)n One carbonyl group (carbon is double bonded to oxygen) Other carbons have a hydroxyl (-OH) group attached Backbone is typically unbranched carbon chains in which carbon atoms are linked by single bonds Names are based on number of carbons present o 3 carbon = triose o 4 carbon = tetrose o 5 carbon = pentose o 6 carbon = hexose Most have a sweet taste Freely soluble in water Aldose Versus Ketose Two types of monosaccharides – depends on location of carbonyl group Aldose - carbonyl group is at end of the carbon chain Ketose - carbonyl group is within carbon chain Relationships between monosaccharides (within the aldoses or the ketoses) • Stereoisomers – same composition and order but different molecular arrangements (position of OH groups on the chiral carbons differ) o All monosaccharides are chiral except dihydroxyacetone o Note that dihydroxyacetone does not have D- or L- designation o Monosaccharides with chiral centers occur in optically active forms ▪ D or L is determined by the chiral center most distant from the carbonyl carbon ▪ D (dextarotatory) isomer has –OH group on the right ▪ L (levorotatory) isomer has –OH group on the left ▪ Enantiomers are mirror image molecules • • • Enantiomers – mirror image molecules (D vs L); stereoisomers that are nonsuperimposable mirror images o Based on chiral carbon farthest from the carbonyl group) • Diastereomers – stereoisomers that are not mirror images with different configuration at one or more chiral carbons • Epimers – diastereomers that differ in configuration at a single chiral carbon o o These are a subset of the diastereomers Sugars are not present in solution as linear chains Aldehydes and ketones react with alcohols to form hemiacetals and hemiketals Intramolecular reaction in a pentose or hexose forms cyclic structure Carbonyl group forms a covalent bond with the oxygen of a hydroxyl group in the chain General reaction between aldehydes or ketones with alcohols to form hemiacetals or hemiketals We usually draw sugars in linear form but they are usually in the cyclic form Cyclization of D-glucose In the Haworth projections, OH groups below the plane appear on the right side of the Fischer projection The carbonyl carbon is now chiral and is called the anomeric carbon Cyclic Sugars Can Form Pyran or Furan Rings Renders C-1 as chiral (the anomeric carbon) – anomers differ only at conformation at this carbon Position of the new –OH group (former carbonyl oxygen) determines if anomer is a or b (beta) stereoisomer If –OH is on the opposite side of the ring from the CH2OH group (C-6), the configuration is a, if it is on the same side it is the b configuration (6 rings membered on the left, 5 membered on the right) Disaccharides • Monosaccharide units are joined by glycosidic bonds between an anomeric carbon and a hydroxyl carbon or another anomeric carbon • The anomeric carbon of one or both monosaccharides is involved in the glycosidic bond • • • • Sugar monomers can be the same or different Most common linkages are 1→1, 1→2, 1→4, and 1→6 The anomeric carbon of at least one sugar is involved in the glycosidic bond Carbohydrates Major Points Position of carbonyl group determines aldose versus ketose D versus L sugars Anomeric carbon and a versus b Know the structure of glucose! Polysaccharides Also called glycans Chains of monosaccharides Storage (store energy/fuel) or structural Homopolysaccharide or heteropolysaccharide Linear or branched Glycogen and starch • Important for storing glucose • Energy source in plants (starch) and animals (glycogen) • Branching provides many ends for removal of glucose units Glycogen Energy storage in animals Branched homopolysaccharide of glucose Glucose monomers form (a1→4) linked chains Branchpoints with (a1→6) linkages about every 8 residues Molecular weight can be very high (millions) and can form compact granules Specific enzymes to synthesize and degrade linear chain versus branches o Glycogen synthase builds linear chain o Glycogen branching enzyme adds branches o Glycogen phosphorylase degrades linear chain o Glycogen debranching enzyme removes branches o Enzymes are highly regulated Starch Used for energy storage in plants Polymer of two chains: amylose and amylopectin Amylose: continuous unbranched chain of a-D-glucose units joined by (a1→4) linkage (a=alpha) Amylopectin: highly branched consisting of D-glucose units joined by (a1→4) linkages with branches created by (a1→6) linkages occurring every 10-20 residues Less branched overall than glycogen Structure of amylose and amylopectin: Amylopectin branching: Amylose has a helical structure: Representation of Starch: o Glycogen has a similar structure but with more branching. Glucose residues are removed one at a time from the nonreducing ends of the branches. Glycogen Versus Starch: Both are branched chains of glucose o Glycogen is for energy storage in animals and starch is for energy storage in plants Glycogen o Glucose monomers joined by (a1→4) linkages o Branchpoints with (a1→6) linkages about every 8 residues Starch o Polymer of amylose and amylopectin o Amylose is a continuous unbranched chain of D-glucose units joined by (a1→4) linkages o branchpoints with by (a1→6) linkages occurring every 10-20 residues Glycogen Storage Diseases Why isn’t glucose stored as a monomer? Glucose contributes to the osmolarity of the cell but glycogen doesn’t (not significantly) because it is insoluble Glucose concentration ~ 0.4 M Glycogen ~0.01 mM = 4 x 107 fold difference in contribution to osmolarity High glucose concentration could lead to cell rupture, and concentration gradient would be prohibitively high for glucose uptake Cellulose The major structural component of plants, especially wood and plant fibers Most abundant natural polymer on earth Linear, unbranched polymer of D-glucose units with b(1→4) linkages Fully extended conformation with alternative glucose residues flipped 180° Extensive intra- and intermolecular hydrogen bonding between chains gives strength Insoluble in water Can’t be broken down by most animals Structure o Extended H-bonding between chains gives fibers great strength o b linkage gives more linear chains so can pack together well o o The ability to digest cellulose is special o Fungi, bacteria, and protozoa secrete cellulases that allow them to use wood as a source of glucose o The only vertebrates that can use cellulose are cattle and other ruminants o Rumen has microbial symbionts that have cellulases to degrade cellulose o Termites also have microbes that secrete cellulases Glycoconjugates Proteoglycans o Sulfated glycosaminoglycan chains joined covalently to a membrane protein or secreted protein o Bind to molecules via electrostatic interactions o Major components of all extracellular matrices Glycoproteins o Proteins with small oligosaccharides of varying complexity covalently attached via anomeric carbon o Oligosaccharides are very heterogeneous and rich in information Glycolipids o Membrane lipids in which hydrophilic head groups are oligosaccharides o Play a role in signal transduction Glycoproteins Oligosaccharides chains (glycans) covalently attached to proteins, can be simple or complex Proteins can have multiple oligosaccharides attached Carbohydrate can constitute from 1-70% of the mass of the glycoprotein Glycans are usually smaller, branched, and more structurally diverse than glycosaminoglycans of proteoglycans Sugars can be linked to protein via O-glycosidic linkage and N-glycosidic linkage Half of all proteins are glycosylated and 1% of mammalian genes are enzymes involved in carbohydrate synthesis and attachment Linkages of glycoproteins: o N-linked oligosaccharides are covalently attached to the NH group of asparagine o O-linked oligosaccharides are covalently attached to the OH group of serine or threonine Advantages of glycosylation Alter the polarity and solubility of protein Destination labels Quality control Induce changes in protein structure to favor formation of localized rodlike structures Protect from degradation Cells use specific oligosaccharides to encode important information Intracellular targeting of proteins Cell-cell interactions Cell differentiation Tissue development Extracellular signals Structural diversity of carbohydrates = more information Can be branched Can be bound by a number of linkages With the number of monosaccharides available can have billions (109) of possible hexameric combinations Only 6.4 x 107 (206) possible hexapeptides Only 4,096 (46) possible hexanucleotides Oligosaccharides presents a unique, three-dimensional face (the sugar code) to proteins they interact with Lectins: proteins that read the sugar code Bind very specifically and with good affinity to different oligosaccharides A single lectin may have multiple interactions with an oligosaccharide through multiple carbohydrate binding domains Cell-cell recognition Signaling Adhesion processes Intracellular targeting of newly synthesized proteins Lectin specificity is imparted by many interactions o There can be many interactions between a protein and even a small carbohydrate o Lectins may have multiple carbohydrate-binding domains to increase the strength and specificity of interaction with an oligosaccharide o Lectins may also interact with carbohydrates in less specific ways o o • • Carbohydrates on other biomolecules Carbohydrates can be added to lipids and proteins This can provide additional information Practice problem 1: For glucose, list which of the aldohexoses below are stereoisomers, enantiomers, diastereomers, and epimers. Stereoisomers: All of the above are stereoisomers of glucose and the L-forms are as well. All of the aldoses that have the same number of carbons are stereoisomers of each other; likewise, all of the ketoses would be stereoisomers of each other. They differ in the configuration at one or more carbons but are all the same formula and have the carbonyl in the same position. Enantiomers: The enantiomer of glucose is not shown. Enantiomer refers to the D or L form. The aldoses shown above are all D-enantiomers. The fifth carbon here (carbon 1 is at the top is the chiral carbon that is farthest from the carbonyl carbon and the configuration at this carbon determines whether it is the D or L enantiomer. The D enantiomers have the OH group to the right and the L enantiomer would have it to the left. The D and L form of a monosaccharide are mirror images of each other (see D and L fructose below). Diastereomers: For glucose, all of the aldoses above are diastereomers. They differ at the configuration at one or more chiral carbon. Note that D and L enantiomers are not considered diastereomers because they are mirror images of each other. Diastereomers are not mirror images. Epimer: Allose (C3), mannose (C2), and galactose (C4) are epimers that have opposite configuration from glucose at a single carbon as indicated. Note that they are diastereomers to each other. Practice problem 2: Which carbon is the anomeric carbon and is this the a or b stereoisomer? The carbon connected to the right of the ring oxygen is the anomeric carbon. This was the carbonyl carbon in the linear form. This is the b stereoisomer because the OH group points up in the same direction as the CH2OH group that extends from the ring (C6).
