BCH 4053 Biochemistry IFall 2001
Dr. Michael Blaber
- Monosaccharides. "Simple sugars" with the formula (C • H2O)n. The word carbohydrate refers to the fact that this class of molecules consists of hydrates of carbon.
- Oligosaccharides. Polymeric molecule of sugar comprising 2-10 covalently linked monosaccharide units. Often found conjugated to other classes of biomolecules including lipids and proteins.
- Polysaccharides. Larger polymers of simple sugars. On the order of hundreds to thousands of monosaccharide units as linear or branched polymers.
- Most taste sweet.
- Contain 3-7 carbon atoms.
- Are either an aldose or a ketose
- Aldoses contain an aldehyde functional group
- Ketoses contain a ketone functional group
- The number of carbons, and the functional group, are specified in the nomenclature for monosaccharides. The letters "ul" are sometimes inserted into the name (rather than the word "keto") to indicate the monosaccharide is a ketose.
Number of Carbons
(Generic monosaccharide name)
Aldose Functional Group
Ketone Functional Group
In addition to the general name of the monosaccharide, the stereochemistry about each chiral center is important.
Fischer projection method of drawing such molecules
- We need a way to specify both the chirality and the particular carbon in the monosaccharide molecule for each chiral center
- We need a convenient way to represent such stereochemical features when drawing monosaccharides
- The solution to these problems is the
- The carbonyl group of the keto or aldose functional group is considered to be closest to the "start" of the carbon chain. The carbon thus identified as the "first" carbon in the chain is carbon #1. The remaining carbons are numbered sequentially.
- The "highest numbered" asymmetric carbon (i.e. furthest from the "start" carbon) determines whether the monosaccharide is the "D" or "L" isomer. In Fischer Projections, the "D" isomer will have the hydroxyl (-OH) functional group located on the right-hand side of the chiral C. Note that the D/L nomenclature has nothing to do with optical rotation activity of the structure; this is indicated by the use of (+) or (-).
The majority of saccharides in nature have the "D" isomer
Common names are used to identify the chirality of lower-numbered carbons in the structure.
- In the above example of aldotetroses:
different common names
- Carbon #1 is at the end closest to the aldehyde carbonyl
- Carbon #3 is the highest numbered carbon that is chiral (carbon 4 is not chiral because it contains two hydrogens)
- The "D" or "L" nomenclature therefore refers to the chirality of carabon #3. The "D" form has the OH group on the right-hand side of carbon #3; the "L" form has the OH group on the left-hand side.
- Carbon #2 is chiral, and the different isomers of this aldotetrose (at locations other than the highest chiral carbon) are indicated by
Here are some examples of Fischer projections for some ketopentoses:
- Carbon #1 is the end closest to the keto group
- Carbon #4 is the highest chiral carbon and determines the "L" or "D" isomer nomenclature for the saccharide
- Carbon #3 is also chiral, and its chirality determines the common name
- Carbon #2 is not chiral, neither is carbon 1, or carbon 5. For ketoses, the smallest chain length that would include a chiral center is four carbons (a ketotetrose, or tetrulose).
- If isomers are mirror images, then they are enantiomers
- If isomers contain more than one chiral center and are not mirror images, then they are diastereomers
- If carbohydrate isomers differ at only a single chiral center, then they are epimers. (epimers are a special category of diastereomers)
Cyclic Structures and Anomeric Forms
Alcohols react readily with aldehydes to form hemiacetals:
- This reaction is promoted in the presence of either acid or base
- One of the subtleties of this reaction involves the stereochemistry of the aldehyde and keto carbon - it goes from being achiral to chiral.
Likewise, alcohols react with ketones to produce hemiketals:
Since aldoses and ketoses contain alcohol groups, in addition to their aldehyde or ketone groups, they have the potential to react to form cyclic forms.
- "Pyranose" is used to refer to the pyran ring structure (6-membered ring with 5 carbons and 1 oxygen)
- For five membered rings (four carbons and 1 oxygen) the structure is a furanose ring.
- Cyclization is reversible
- The resulting chirality of the aldehyde carbon (or keto carbon in ketoses) in the cyclic structure can be either the a- or b- form. This carbon is termed the anomeric carbon, and the a- and b- forms are anomers.
- The ring structure representations are termed "Haworth Projections"
- Cyclic structures can also be represented using Fischer diagrams
Alternative ring structures
- Glucose has a variety of alcohol functional groups, and is able to form alternative hemiacetal ring structures
- The 5C-OH can react with the aldehyde forming the above pyranose ring
- The 4C-OH can react with the aldehyde forming a five-membered furanose ring
- The carbon atoms in the ring are sp3 hybrid orbitals, and tetrahedral geometry
- The oxygen in the ring is also sp3, and tetrahedral
- Thus, the ring structures cannot be planar (that would require trigonal planar geometry, or sp2 hybrid orbitals, for the atoms in the ring)
- What do the rings actually look like?
- There is a "boat" and a "chair" structure. There are two different orientations of the functional groups bonded to the ring carbons:
- If they point in the general plane of the ring, they are said to be in the "
- If they point in an orientation perpendicular to the general plane of the ring, they are side to be in the "axial" position
- Notice that the chair can have two different conformations. The principle effect of the alternative conformations is to change the axial versus equatorial orientations for the carbon functional groups
Functional groups in the axial position are somewhat crowded together, whereas, the same functional groups in the equatorial position are separated from each other.
The preferred chair conformation is the one that minimizes close contacts between large functional groups - these will preferentially occupy the equatorial position
If you look at various cyclic saccharide structures, those with alternating hydroxyl groups will minimize steric clashes of these groups when in the axial configuration
Of all the D-aldohexoses, only b-D-glucopyranose (b-D-glucose) is able to adopt a chair conformation with bulky groups in the axial orientation
Derivatives of Monosaccharides
. Sugars with a free aldehyde can function as reducing agents by having the aldehyde group oxidized to a carboxylic acid (as in any redox reaction, for this to happen something else must be reduced). Such sugars are called reducing sugars.
- Addition of alkaline copper sulfate will result in a red precipitate of copper(I)oxide if reducing sugars (sugars with free aldehydes are present). This is a diagnostic test for sugar in the blood of diabetic patients
- Sugar alcohols. With an appropriate reducing agent, the carbonyl group of aldoses and ketoses can be reduced to an alcohol. Such reduction prevents the cyclization of the saccharide (which requires a keto group). The nomenclature to indicate sugar alcohols is the -ol ending
- Deoxy sugars. Monosaccharides with one or more hydroxyl groups replaced by a hydrogen. 2-deoxy-D-ribose is a key component of DNA (deoxy-ribo-nucleic acids)
- Sugar esters. Phosphate esters are high-energy bonds that play an essential role in thermodynamically coupled reactions. ATP (adenosine triphophate) is a phosphate ester to a ribose saccharide.
- Amino sugars. Some saccharides have an amino (-NH2) group instead of a hydroxyl group. Amino sugars are found in bacterial cell walls, and the exoskeletons of insects and crustaceans.
- Acetals, Ketals and Glycosides. Hemiacetals and hemiketals (found in cylic forms of saccharides) can react with alcohols (under acidic conditions) to form acetals and ketals. The alcohol can be from another saccharide, and form a glycosidic bond between two saccharides. This is a condensation reaction (releases H2O) similar to the formation of peptide bonds.
The basic monomeric units that are used to build up complex oligosaccharides are essentially limited to:
- Hexoses. Glucose, mannose, galactose (all aldoses), and fructose (ketose)
- Pentoses. Ribose, xylose (both aldoses)
Lactose. This disaccharide is a dimer comprised of a galactose linked to glucose via a b-1-4 glycosidic bond. "Milk sugar" - it is the principle carbohydrate of milk. Must be broken down into galactose and glucose by the enzyme lactase.
This disaccharide is glucose-a-1,2-fructose. "Table sugar". No free anomeric carbon, therefore, not a reducing sugar.
This disaccharide is glucose-a-1,4 glucose. "Grain sugar". Has a free anomeric carbon and is therefore a reducing sugar.
Plants produce various higher oligosaccharides. Humans may or may not have the enzymes necessary to break them down into useful monosaccharides (i.e. to break specific glycosidic linkages). However, bacteria in our intestine may have such enzymes. Therefore, if you eat some of such complex carbohydrates, you are simply nourishing the bacteria in your intestine. They will thank you by producing more of their own waste products - including certain gases.
The majority of carbohydrate material in nature occurs in the form of polysaccharides (also known as glycans). Other molecules that contain polysaccharide structures are also referred to as polysaccharides.
- Homopolysaccharide. A polysaccharide whose monosaccharide units are identical.
- Heteropolysaccharide. A polysaccharide made up of different monosaccharides
Homopolysaccharides composed of glucose are called glucans; those composed of mannose are called mannans; etc.
- The most common constituent of polysaccharides is
Glycosidic linkages involve only one anomeric carbon (keto or aldehyde) per monosaccharide. However, there are several potential hydroxyl acceptor groups on a given monosaccharide. Thus, polysaccharides can be branched as well as linear.
glucan that has two polysaccharide forms: one is a linear molecule with a-1-4 linkages called amylose. The other is a branched form of amylose, where the branches have a-1-6 linkages, called amylopectin.
- The characterization of polysaccharides includes their length, the type of monosaccharide units, the linkages and branched nature
- Starch is a
Polysaccharides have historically been described as having functions related to storage, structure and protection. But, the full range of functions of polysaccharides have not yet been fully determined.
starch. One large polymer has a much lower osmotic pressure than a bunch of monomeric molecules. Glucose is therefore stored as a polymer. Before use, the starch (amylose, and amylopectin) must be broken down into individual D-glucose units by starch phosphorylase:
- The most common storage polysaccharide in plants is
- The major form of storage polysaccharide in animals is glycogen (found in the liver and skeletal muscle). It is highly branched with a-1-6 branches. It is hydrolyzed by a- and b-amylases to yield glucose and maltose (glucose-a-1-4-glucose disaccharide). It can also be hydrolyzed by glycogen phosphorylase (in liver and muscle) to release glucose-1-phosphate.
- Yeast and bacteria make dextran as a storage polysaccharide. It is composed of a-1-6 linkages of D-glucose, with branched chains (1-2, 1-3 or 1-4 linkages between glucose units). Important component of dental plaque (from bacteria).
- Cellulose. The most abundant natural polymer found in the world. Found in the cell wall of almost all plants, it provides physical structure and strength. Primary difference between cellulose and starch is that cellulose glycosidic linkages are b-1-4 linkages. The a-1-4 linkages in starch give the polysaccharide a helical twist. The b-1-4 linkages in cellulose give the polysaccharide an extended ribbon conformation. Separate chains of cellulose can hydrogen bond and this provides a network of strong intermolecular interactions giving cellulose its strength.
- Cellulose is thus resistant to hydrolysis. A special enzyme (cellulase) is needed to hydrolyze the glycosidic bond. Some bacteria make cellulase and can therefore "eat" cellulose
- Chitin. Similar to cellulose. Made in cell walls of fungi and exoskeletons of crustaceans, insects and spiders. Main difference is the hydroxyl at the 2 position is replaced by -NHCOCH3. Monomeric unit is therefore N-acetyl-D-glucosamine.
- Alginate. Made by marine brown algae. Binds metal ions, and is necessary to form organized polymeric structures that manifest as physical "gels".
- Agarose. Made by marine red algae. Forms edible gel, not unlike gelatin.
- Glycosaminoglycans. Polysaccharide with amino sugars and sulfate containing groups. Results in negatively charged polymers. Natural anticoagulant (inhibits blood clotting). Chondroitins and keratin sulfates fall into this group of polysaccharide and are in important component of skin and tendons.
© 2001 Dr. Michael Blaber