Learning Goals/Objectives for Chapter 3A: After class and this reading, students will be able to
If you are a Biochemistry Major and took BCHM 317 last semester, please take the following 3 question survey before the start of the next class: Survey: Proteins - Content Overlap
The link below is an extraordinary and free resource on glycobiology. It defines the word "glycan" as a "generic term for any sugar or assembly of sugars, in free form or attached to another molecule" and "is used interchangeably ... with saccharide or carbohydrate."
Simple sugars can be defined as polyhydroxy aldehydes or ketones. Hence the simplest sugars contain at least three carbons. The most common are the aldo- and keto-trioses, tetroses, pentoses, and hexoses. The simplest 3C sugars are glyceraldehye and dihydroxyacetone.
Glucose, an aldo-hexose, is a central sugar in metabolism. It and other 5 and 6C sugars can cyclize through intramolecular nucleophilic attack of one of the OH's on the carbonyl C of the aldehyde or ketone. Such intramolecular reactions occur if stable 5 or 6 member rings can form. The resulting rings are labeled furanose (5 member) or pyranose (6 member) based on their similarity to furan and pyran. On nucleophilic attack to form the ring, the carbonyl O becomes an OH which points either below the ring (a anomer) or above the ring (b anomer).
Figure: Sugar Ring Formation and Representations
Monosaccharides in solution exist as equilbrium mixtures of the straight and cyclic forms. In solution, glucose (Glc) is mostly in the pyranose form, fructose is 67% pyranose and 33% furanose, and ribose is 75% furanose and 25% pyranose. However, in polysaccharides, Glc is exclusively pyranose and fructose and ribose are furanoses.
Sugars can be drawn in the straight chain form as either Fisher projections or perspective structural formulas.
In the Fisher projection, the vertical bonds point down into the plane of the paper. That's easy to visualize for 3C molecules. but more complicated for bigger molecules. For those draw a wedge and dash line drawing of the molecule. When determining the orientation of the OHs on each C, orient the wedge and dash drawing in your mind so that the C atoms adjacent to the one of interest are pointing down. Sighting towards the carbonyl C, if the OH is pointing to the right in the Fisher project, it should be pointing to the right in the wedge and dash drawing, as shown below for D-erthyrose and D-glucose.
Figure: Orienting OH groups in wedge and dashing drawings of simple straight chain sugars
Cyclic forms can be drawn either as the Haworth projections, which shows the molecule as cyclic and planar with substituents above or below the ring) or the more plausible bent forms (showing Glc in the chair or boat conformations, for example). b-D-glucopyranose is the only aldohexose which can be drawn with all its bulky substituents (OH and CH2OH) in equatorial positions, which probably accounts for its widespread prevalence in nature.
Haworth projections are more realistic than the Fisher projections, but you should be able to draw both structures. In general, if a substituent points to the right in the Fisher structure, it points down in the Haworth. if it points left, it points up. In general, the OH on the a-anomer points down (ants down) while on the b-anomer it points up (butterflies up).
Jmol: Fisher to Ring Structures of Glucose
Figure: A more rigorous view of the relationship between the anomeric OH and the OH on the last chiral C of a sugar.
In the Haworth projections, the bulky R group of the next carbon after the carbon whose OH group engaged in a nucleop hilic attach on the carbonyl carbon to form the ring O is pointed up if the OH engaged in the attach was on the right hand side in the straight chain Fisher diagram (as in a-D-glucopyranose above when the CH2OH group is up) but is pointed down if the OH engaged in the attach was on the left hand side in the straight chain Fisher diagram (as in a-D-galactofuranose above when the (CHOH)CH2OH group is down). The rest of the OH groups still follow the simple rule that if they are pointing to the right in the Fisher straight chain form, they point down in the Haworth form.
The most common monosaccharides (other than glyceraldehyde and dihydroxyacetone) which you need to know are shown below.
The mirror image of D-Glc is L-Glc. For common sugars, the prefix D and L refer to the center of asymmetry most remote from the aldehyde or ketone. By convention, all chiral centers are related to D- glyceraldehyde, so sugar isomers related to D-glyceraldehyde at their last asymmetric center are D sugars.
Sugars can exists as either configurational isomers (interconverted only by breaking covalent bonds) and conformational isomers. The figure below reviews different types of isomers.
The configurational isomers include enantiomers (stereoisomers that are mirror images of each other), diastereomers (stereoisomers that are not mirror images), epimers (diastereomers that differ at one stereocenter), and anomers (a special form of stereoisomer, diastereomer, and epimer that differ only in the configuration around the carbon which was attacked in the intramolecular nucleophilic attack to produces the a and b isomers).
Sugars can also exist as conformational isomers, which interchange without breaking covalent bonds. These include chair and boat conformations of the cyclic sugars.
Many derivatives of monosaccharides are found in nature. These include
Figure: Sugar Derivatives
In the above figure, N-acetylmuramic acid, found in bacterial cell walls, consists of GlcNAc in ether link at C3 with lactate, while N-acetylneuraminic acid results from an intramolecular cyclization of a condensation product of ManNAc and pyruvate.
Figure: Is sialic acid the big difference between humans and chimps?
What happens when non-vegan humans eat animal products (meat, milk) with N-glycoyl neuraminic acids (Neu5Gc)? Varki et al found that some gets incorporated into human membrane glycans (see next Chapter). Sialic acids on surface proteins can serve as "receptors" that allowing binding of self-cells as well as foreign cells or proteins that have evolved to bind them. Byres et al discovered that a toxin, SubAB, secreted by E. Coli 0157, can bind Neu5Gc. Hence eating meat products can make us more susceptible to bacteria that recognize Neu5Gc.
Chemistry of Sugars - Hemiacetals, Acetals, Disaccharides,
Monosaccharides that contain aldehydes can cyclize through intramolecular nucleophilic attack of an OH at the carbonyl carbon in an addition reaction to form a hemiacetal (hemiketal if attack on a ketone). On the addition of acid (which protonates the anomeric OH, forming water as a potential leaving group), another alcohol can add forming an acetal (or ketal from a ketone) with water leaving.
If the other alcohol is a second monosaccharide, a dissacharide results. The acetal (or ketal) link bonding to the two monosaccharides is called a glycosidic link. Links between the two sugars can be either a (if the OH on C1 involved in the glycosidic link is pointing down) or b (if the O on C1 involved in the glycosidic link is pointing up). Since sugars contain so many OH groups which can act as the "second" alcohol in acetal (or ketal) formation, links between sugars can be quite diverse. These include a and b forms of 1-2, 1-3, 1-4, 1-5, 1-6, 2-2, etc. links. For example:
The glycosidic (acetal or ketal) link can be cleaved by hydrolysis, just as the peptide bond in proteins.
Figure: A closer look at reducing and nonreducing sugars: lactose and maltose
Jmol: D Glucose Jmol: Acetal Formation
CHO Web Links
Moodle Online Quiz (PASSWORD PROTECTED): CARBOHYDRATES 1
Byres, E. et al. Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin. Nature 456, 648-652 (2008)
Pam Tangvoranuntakul, Pascal Gagneux, Sandra Diaz, Sandra Diaz, Ajit Varki, and Elaine Muchmore
and Elaine Muchmore. Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. PNAS 2003 100:12045-12050
Cramer and Truhlar. Quantum Chemical Conformational Analysis of Glucose in Aqueous solutions. J. Am. Chem. Soc. 115, pg 5745 (1993)