BioC 3021 Notes - Lecture 10: Carbohydrates PDF

BioC 3021 Notes Robert Roon Lecture 10: Carbohydrates Slide 1. Carbohydrates In this lecture, we will consider another major class of biomolecules, the carbohydrates. Slide 2. Carbohydrate Definition Most carbohydrates are polyhydroxy aldehydes or ketones...

BioC 3021 Notes Robert Roon Lecture 10: Carbohydrates Slide 1. Carbohydrates In this lecture, we will consider another major class of biomolecules, the carbohydrates. Slide 2. Carbohydrate Definition Most carbohydrates are polyhydroxy aldehydes or ketones. They often have the general empirical formula: [CH2O]n. Their name derives from a formula that has the proportions of one carbon atom and one water molecule—carbo for carbon—hydrate for water. Early chemists thought that this might have some significance. Even though that is not the case, the name has stuck. Slide 3. Classification of Carbohydrates Monosaccharides are the basic building blocks from which all carbohydrate polymers are constructed. The term aldose is used to describe those monosaccharides that have an aldehyde functional group. The term ketose is used for monosaccharides that have a ketone group. Carbohydrates are also classified by the number of carbon atoms that they contain. Trioses have three carbons, tetroses have four, pentoses have five, hexoses have six and heptoses have seven. These terms are combined to give a more complete description of a monosaccharide. For example, glucose is an aldohexose. Slide 4. Monosaccharides, Oligosaccharides and Polysaccharides There are specific terms that describe the number of monomer units that are covalently linked to each other. Monosaccharides have one unit, Oligosaccharides have 2-10 units, and 1 BioC 3021 Notes Robert Roon Polysaccharides can have up to 1000 or more units. Within the oligosaccharide range, one commonly encounters disaccharides that have two monosaccharide units, trisaccharides that have three, and tetrasaccharides that have four. Slide 5. Enantiomers As with amino acids, many carbohydrates have centers of asymmetry (chiral centers). Enantiomers are isomers that are exact mirror images of each other. In reference to carbohydrate enantiomers, the designators D- and L- are used. The trioses, D- and L-glyceraldehyde are the simplest carbohydrate enantiomers. Most, but not all of the naturally occurring carbohydrates are D- isomers. Carbohydrates with chiral centers often rotate the plane of polarized light. This property was used by early carbohydrate chemists to help characterize various carbohydrates and to track the reactions they undergo. When two enantiomers of the same compound are mixed in equal amounts, the effects on polarized light are canceled out, and no rotation occurs. A mixture of equal amounts of two enantiomers is called a racemic mixture. Slide 6. Perspective Formulas Perspective formulas designate D- and L-isomers. With perspective formulas, the two bold groups radiating from a central carbon are coming out of the plane of the screen, and the two groups in regular type are going into the plane of the screen. When Fischer projection formulas are used, these same orientations of the carbon atoms are assumed even though they are not shown. Slide 7. Configuration vs. Conformation The 3-dimensional arrangements of substituent groups in space 2 BioC 3021 Notes Robert Roon about a chiral center are referred to as configurations. The different spatial arrangements of a molecule, resulting from free rotation about carbon-carbon single bonds, are called conformations. Slide 8. Epimers Epimers are monosaccharides that differ in stereochemistry at only one chiral carbon. Epimers are generally not mirror images of each other (except for trioses) and are not chemically equivalent to each other. That is, epimers generally are different compounds with specific names and varying chemical reactivities. Slide 9. Number of Isomers A monosaccharide will have 2N isomers, where N equals the number of centers of asymmetry. In the example shown here, an aldohexose will have four chiral centers corresponding to the middle four carbons, each of which are attached to four different substituents. (The top and bottom carbons are not chiral because they do not have four different substituents.) In the example of aldohexoses, there will be 2N isomers (equaling 24), which is 16 isomers or 8 D-L pairs. -Aldotrioses have one asymmetric center and 2 possible isomers. -Aldotetroses have two asymmetric centers and 4 possible isomers. (22) -Aldopentoses have three asymmetric centers and 8 possible isomers. (23) -Aldohexoses have four asymmetric centers and 16 possible isomers. (24) Slide 10. Aldotrioses and Aldotetroses Here, we see the chiral centers in aldotrioses and aldotetroses. The prefix D- or L- for these compounds is derived from the lowest center of asymmetry in the Fischer projection. According to convention, the most oxidized functional group (in this case, the 3 BioC 3021 Notes Robert Roon aldehyde) is placed at the top of the compound. If the –OH group is to the right in the lowest center of asymmetry, then the compound is designated “D”. If the –OH group is to the left in the lowest center of asymmetry, then the compound is designated “L”. Slide 11. Aldotetroses and Aldopentoses Shown here on the lower half of the slide are the four D-isomers of aldopentoses. There are also four possible L-isomers. Slide 12. D-Aldohexoses This slide shows the eight D-isomers of aldohexoses. Again, there are also eight L-isomers. The structures of the shaded compounds glucose, galactose and mannose should be firmly deposited into our memory bank, because these compounds are very common in nature. (I personally like the sound of gulose because it has a sort of horror show ring to it—however, that is probably not a good reason to learn its structure.) Slide 13. Mutarotation of D-Glucose In water, glucose spontaneously reacts to form two cyclic (six membered pyranose ring) products. These a- and b-glucopyranose compounds are referred to as a- and b-anomers. This process of interconversion of α- and β-anomers with the open chain form is referred to as mutarotation. Here, you can see the convention for converting from the linear Fischer formula to the cyclic Halworth formula. The convention is to have the number 6 carbon (hydroxymethyl group) radiating up for D-aldohexoses. The hydroxyl groups at carbons 2 and 4, which are to the right in the Fischer formula, radiate down in the Halworth formula. The hydroxyl group at carbon 3, which is to the left in the Fischer formula, radiates up in the Halworth formula. The hydroxyl group at position 5 becomes the ring oxygen, and so has no chirality. 4 BioC 3021 Notes Robert Roon The aldehyde group, at position 1 in the open chain Fischer projection, is converted to a new (anomeric) hydroxyl group that has chirality. If the anomeric hydroxyl radiates down, it is called an α-anomer. If it radiates up, it is referred to as a β-anomer. Slide 14. Anomers The α- and β-anomers at position 1 differ only in their configuration about the new asymmetric (anomeric) center that is formed when the open chain form of a monosaccharide reacts to form cyclic products. Slide 15. Mutarotation The process of interconversion of α- and β-anomers through the intermediate formation of an open chain form is called mutarotation. In solution, monosaccharides in the open chain form are constantly equilibrating with the cyclic α- and β-anomers. Slide 16. Hemiacetal Formation The cyclization of an aldose such as glucose occurs when an alcohol group reacts with an aldehyde group in the same molecule. This is the chemical equivalent of the formation of a hemiacetal. Slide 17. Hemiketal Formation The cyclization of a ketose such as fructose occurs when an alcohol group reacts with a ketone group in the same molecule. This is the chemical equivalent of the formation of a hemiketal. Slide 18. Acetal Formation After reaction of a hemiacetal with a second alcohol molecule, the product is an acetal. When two cyclized carbohydrates react to form a disaccharide, it is the equivalent to the formation of an acetal. Unlike hemiacetals, which are constantly equilibrating with the aldehyde and alcohol, the acetal derivatives are generally very stable. 5 BioC 3021 Notes Robert Roon Slide 19. Reducing and Non-Reducing Sugars There is a classic test (Fehling’s reagent) for the identification of carbohydrates that can mutarotate through the open chain form to produce an aldehyde. Such open chain aldehydes can reduce Cu2+, and in the process are oxidized to a carboxylic acid. Most monosaccharides are reducing compounds, but if the anomeric hydroxyl group is methylated or locked in an acetal structure, they become non-reducing compounds. Slide 20. Ketoses Ketoses have the carbonyl carbon at the #2 position of the monosaccharide. They have one less asymmetric center than the equivalent aldose molecule. You should learn the structure of fructose. You probably eat some fructose every day, and so, like glucose, it should be part of your chemical vocabulary. Slide 21. Mutarotation of Fructose As with aldoses, ketose compounds such as fructose can mutarotate to form cyclic derivatives. In the example shown, fructose cyclizes to form an α-D-fructofuranose (a five-membered furanose ring) anomer. The Fructose molecule can also cyclize to form a six-membered pyranose ring. The distribution of fructose between the open chain form and the various possible cyclic structures depends on the relative energy levels of those structures. The form with the lowest energy level will have the greatest concentration at equilibrium. Slide 22. Cyclic Forms of Fructose In this slide, you can see the various pyranose (six-membered) and furanose (five-membered) ring forms of fructose. As with aldoses, the designators α− and β− refer to the anomeric position, which is the new hydroxyl group produced when the cyclic derivative is formed. If the anomeric -OH goes down, it is an α−anomer. If the anomeric -OH goes up, it is a β−anomer. 6 BioC 3021 Notes Robert Roon Slide 23. Conformational Structure Carbohydrate molecules also equilibrate between various conformations--different arrangements of the molecule in space resulting from rotation about C-C bonds. The preferred conformation of a carbohydrate is the one with the lowest energy level. For aldohexoses, the distribution between various chair and boat conformations depends on which conformation exhibits the least steric hindrance. Slide 24. Steric Hindrance The term steric hindrance refers to negative interactions that can occur between two functional groups in a molecule. This slide shows two bulky groups in proximity to one another. If the groups are very large, certain conformations might be impossible because the two groups would be competing for the same space. Even when that is not the case, it is generally true that bulky groups are more stable when they are not in close proximity. In general, conformations that minimize steric hindrance tend to predominate. In monosaccharides, that can exist in various conformations. The distance between bulky groups is often greater when both groups occupy the equatorial position. Slide 25. Chair and Boat Forms of Glucose Here, we see the two common carbohydrate conformations, which are designated chair and boat forms. Groups that radiate out toward the midline of these conformations are referred to as occupying the equatorial position (designated e). Groups that radiate up or down are said to occur in the axial position (designated a). Again, the distribution of a monosaccharide into various chair and boat forms favors the form with the lowest energy level, which in turn is dependent on minimizing steric hindrance. 7 BioC 3021 Notes Robert Roon Slide 26. Methylated Anomers of Glucose Carbohydrates can be selectively methylated at the anomeric hydroxyl. The methylation of a sugar locks the cyclic forms into either the α− and β− anomer so there is no mutarotation. In addition, the methylated sugar becomes non-reducing because it cannot achieve the open chain form. That is, the methylated sugar cannot react with oxidizing agents because these reactions need a free aldehyde group in order to proceed. Slide 27. Deoxysugars Deoxysugars lack a hydroxyl group at one of their carbons. Ribose and deoxy-ribose are components of RNA and DNA. You should probably know the structures of these compounds, because where would you and your future children be without these essential materials? In addition, 2-deoxy-ribose is a prime example of a deoxysugar. It lacks a hydroxyl group at carbon 2. Slide 28. Sugar Phosphates Phosphorylated sugar derivatives have at least one covalently bound phosphate residue. The three phosphorylated compounds shown here are all components of the glycolysis pathway. In general, phosphorylated sugars occur inside of cells where they function as intermediates in biochemical pathways. Slide 29. Sugar Acids Sugar acids contain at least one carboxyl group. Galacturonic acid is a common sugar acid. Sugar acids tend to be components of complex carbohydrate polymers that serve as structural materials in connective tissues and other extracellular polysaccharides. Slide 30. Sugar Alcohols In sugar alcohols, the aldehyde or ketone group is replaced by an additional hydroxy group. The commercial sweetener sorbitol is 8 BioC 3021 Notes Robert Roon an example of a sugar alcohol. Another sugar alcohol is the cyclic polyalcohol, inositol. Inositol serves as a component of phosphoglycerols, and in its phosphorylated form also functions as a biological second messenger. Slide 31. N-Glyosidic Bonds In nucleic acids and nucleotides, a nitrogen atom of an organic base (purine or pyrimidine) is covalently linked to the anomeric group of ribose or deoxy-ribose. Such a linkage is referred to as an N-glycosidic bond. Slide 32. An Alpha-1-4-Glycosidic Bond In disaccharides, oligosaccharides, and polysaccharides, the monosaccharide units are linked to each other by glycosidic bonds. In maltose, two glucopyranose units are joined together in an α- 1,4-glycosidic bond. The glycosidic linkage in maltose is referred to as α-1,4 because it connects the 1 (anomeric) carbon of the glucose unit on the left to the 4 carbon of the glucose unit on the right. The linkage from the anomeric carbon radiates in a downward direction, so it is an α-linkage. Slide 33. Common Disaccharides Common disaccharides include sucrose, lactose and maltose. -Sucrose is the usual food that we purchase when we buy a bag of “sugar” in the store. It is a non-reducing sugar because its two anomeric carbons are linked together so that neither of the anomeric positions can mutarotate into the open chain form. -Lactose is the disaccharide present in mammalian milk. It contains galactose and glucose units joined by a β-1-4 linkage. It is a reducing sugar because the glucose component can mutarotate into the open chain form. -Maltose contains two glucose units connected by an α-1-4- linkage. It is a reducing sugar because the glucose residue on the 9 BioC 3021 Notes Robert Roon right can mutarotate. Maltose units are present in the α-1,4-linked regions of the polysaccharides glycogen and starch. Slide 34. The alpha 1-6-Glycosidic Linkage in Glycogen The human storage polysaccharide glycogen contains about 90% α-1,4 linkages and 10% α-1,6 linkages. The α-1,6-linkages are responsible for the branch points in glycogen. Slide 35. Comparison of Cellulose and Glycogen The structural plant polysaccharide cellulose contains β-1,4 linkages. It forms a sheet-like structure. It is not digestible by humans because we lack the appropriate enzyme for hydrolyzing β-1,4-linked glucose units. Starch and glycogen contain α-1,4- linked glucose units (and α-1,6-linked glucose units) and form spiral structures. These linkages are digestible by human enzymes. Slide 36. Amino Sugars In Amino sugars, an amino group substitutes for one hydroxyl group. The N-acetyl derivatives of glucose and galactose are very common components of proteoglycans and glycoproteins. Slide 37. Acidic Disaccharides Chondroitin 6-sulfate and the other disaccharides shown are common components of Glycosaminoglycans. The negatively charged carboxylate and sulfate components are highlighted in red. Slide 38. The Formation of Nucleotide Sugars The synthesis of carbohydrate polymers is catalyzed by enzymes called glycotransferases. The synthesis of carbohydrate polymers from monomers is accomplished using a variety of nucleotide sugars. Cleavage of the phosphoester linkages helps to drive the process in the direction of polysaccharide synthesis. Slide 39. Common Monosaccharide Derivatives 10 BioC 3021 Notes Robert Roon This figure shows a variety of modified monosaccharides. These compounds often occur as components of polysaccharide structures on cell surface glycoproteins. Slide 40. Human Blood Types Figure 11.18 shows the structure of A, B, and O antigens that are found in humans. These carbohydrate structures are present on cell surfaces, attached to proteins and lipids. They are responsible for variations in human blood types. The use of the proper ABO group in blood transfusions is critical. 11