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7.1: Monosaccharides and Disaccharides

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    14955
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    Search Fundamentals of Biochemistry

    Introduction

    Carbohydrate or glycan biochemistry is very complex and difficult, owing to the stereochemical complexity of simple sugars, the large number of positions on the sugars used to form linkages between other sugars to create polymers, the large number of chemical modification to base sugars, and the lack of a genetic template to instruct glycan polymer formation. It is no wonder that our understanding of complex glycans has developed after that of the chemically simpler polymers like nucleic acids and proteins.

    Essentials of Glycobiology, 3rd edition, is a free online book written by and for those interested in glycobiology. Here are some modern definitions taken directly from the glossary of that book:

    Sugar: A generic term often used to refer to any carbohydrate, but most frequently to low-molecular-weight carbohydrates that are sweet in taste. Table sugar, sucrose, is a nonreducing disaccharide (Fruβ2-1αGlc). Oligosaccharides are sometimes called “sugar chains” and individual monosaccharides in a sugar chain are sometimes referred to as “sugar residues.”

    Carbohydrate: A generic term used interchangeably in this book with sugar, saccharide, or glycan. Includes monosaccharides, oligosaccharides, and polysaccharides, as well as derivatives of these compounds.

    Glycan: A generic term for any sugar or assembly of sugars, in free form or attached to another molecule, used interchangeably with saccharide or carbohydrate.

    Monosaccharides Structures

    The above definition of sugar needs some further nuance. From a chemical perspective, 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 as shown in Figure \(\PageIndex{1}\) below.

    FisherProj_Perspect_3CSugars2.svg
    Figure \(\PageIndex{1}\): Three-carbon sugars

    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 free hydroxyl groups on the carbonyl carbon 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 (α anomer) or above the ring (β anomer).

    Figure \(\PageIndex{2}\) below shows different representations of the linear and cyclic forms of the sugars D-glucose, D-ribose and D-fructose

    glcfrccyclizV2.svg

    Figure \(\PageIndex{2}\): Linear and cyclic forms of D-glucose, D-ribose and D-fructose

    Monosaccharides in solution exist as equilibrium 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 Fischer 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 \(\PageIndex{3}\) below shows how to convert Fisher projections to wedge dash representations.

    SaveFischertoWedge.svg

    Figure \(\PageIndex{3}\): Converting Fisher projections to wedge dash representations.

     

    Figure \(\PageIndex{4}\) below shows an interactive iCn3D model of D-glucose in a linear form.

    Figure \(\PageIndex{4}\): D-glucose (Copyright; author via source).

     

    Orient the molecule as shown in Figure \(\PageIndex{x}\) below, with the carbonyl O pointed at the far right, and compare it to the orientation shown in Figure \(\PageIndex{5}\) to reinforce your understanding of Fisher and wedge/dash projections.

    clipboard_e4399a17849be2424f3813876ca6d1574.png

    Figure \(\PageIndex{5}\):

    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 glucose in the chair or boat conformations, for example). β-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. Figure \(\PageIndex{6}\) shows 4 different representation of glucose.

    glcchair.svg

    Figure \(\PageIndex{6}\): Fisher and cyclic Haworth, chair and wedge/dash representations of glucose

    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 α-anomer points down (αnts down) while on the β-anomer it points up. (βutterflies up) as illustrated in Figure \(\PageIndex{7}\)

    choalphabeta2.svg
    Figure \(\PageIndex{7}\): Alpha and beta Haworth representations of sugars

    In the Haworth projections, the bulky R group of the next carbon after the carbon whose OH group engaged in a nucleophilic 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 α-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 α-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 Fisher structures of most common monosaccharides (other than glyceraldehyde and dihydroxyacetone), which you will encounter most frequently are shown Figure \(\PageIndex{8}\) below.

    sugarsknow.svg

    Figure \(\PageIndex{8}\): Most common monosaccharides discussed in this book

    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.

    Figure \(\PageIndex{9}\) below shows multiple renderings of common hexoses.

    CHOMonomers.svg
    Figure \(\PageIndex{9}\): Multiple renderings of common hexoses

    Isomers

    Sugars can exists as either configurational isomers (interconverted only by breaking covalent bonds) and conformational isomers. Figure \(\PageIndex{10}\) below reviews different types of isomers.

    IsomerFlowChart.svg
    Figure \(\PageIndex{10}\): 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 ep11}\) shows enantiomers, diastereomers, epimers and anomers of 6 carbon sugars.

    sugarisomers.svg
    Figure \(\PageIndex{11}\): Enantiomers, diastereomers, epimers and anomers of 6 carbon sugars.

    Sugars can also exist as conformational isomers, which interchange without breaking covalent bonds. These include chair and boat conformations of the cyclic sugars as shown in Figure \(\PageIndex{12}\) below.

    BetaDGlcChairConformers.svg
    Figure \(\PageIndex{12}\): Conformational isomers of b-D-glucopyranose

    Monosaccharide Derivatives

    Many derivatives of monosaccharides are found in nature. These include

    • oxidized forms in which the aldehyde and/or alcohol functional groups are oxidized to carboxylic acids
    • phosporylated forms in which phosphate is added by ATP to form phosphoester derivatives
    • amine derivatives such as glucosamine or galactosamine
    • acetylated amine derivatives such as N-Acetyl-GlcNAc (GlcNAc) or GalNAc
    • lactone forms (intramolecular esters) in which an OH group attacks a carbonyl C that was previously oxidized to a carboxylic acid
    • condensation products of sugar derivatives with lactate (CH3CHOHCO2-) and pyruvate, (CH3COCO2- ), both from the glycolytic pathway, to form muramic acid and neuraminic acids, (also called sialic acids), respectively.

    Figure \(\PageIndex{13}\) below some simple monosaccharide derivatives.

    sugarderiv.svg
    Figure \(\PageIndex{13}\): Monosaccharide derivatives

    Figure \(\PageIndex{14}\) below shows some addition oxidative derivatives of glucose shown in Fischer projections.

    redoxderivativesofGlc.svg
    Figure \(\PageIndex{14}\): Redox derivatives of glucose

    Another important derivation of monosaccharides sialic acids. One, N-acetylmuramic acid, found in bacterial cell walls, consists of GlcNAc in ether link at C3 with lactate, while another, N-acetylneuraminic acid results from an intramolecular cyclization of a condensation product of ManNAc and pyruvate. These sialic acids are shown in Figure \(\PageIndex{15}\) below.

    SialicAcid.svg
    Figure \(\PageIndex{15}\): Sialic Acids

    Sugars are very complicated as the linkages and substituents are so diverse. Figure \(\PageIndex{16}\) below show difference in sialic acids between humans and chimps.

    sialicacid_Humans_Chimps.svg
    Figure \(\PageIndex{16}\): Sialic acids between humans and chimps.

    What happens when non-vegan humans eat animal products (meat, milk) with N-glycoyl neuraminic acids (Neu5Gc)? Some gets incorporated into human membrane glycans. 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. 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.

    Formation of Hemiacetals, Acetals, and 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. These reactions are shown in Figure \(\PageIndex{17}\) below.

    hemiacetalchemistry.svg
    Figure \(\PageIndex{17}\): Hemiacetal and acetal formation

    If the other alcohol is a second monosaccharide, a disaccharide results. The acetal (or ketal) link bonding to the two monosaccharides is called a glycosidic link. Links between the two sugars can be either α (if the OH on C1 involved in the glycosidic link is pointing down) or β (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 α and β forms of 1-2, 1-3, 1-4, 1-5, 1-6, 2-2, etc. links. Here are examples of disaccharides:

    • maltose: Glc(α 1,4)Glc, which can be considered a disaccharide hydrolysis product of the polysaccharide glycogen or starch (discussed in the section)
    • cellobiose: Glc(Glc(α 1,4)Glc 1,4)Glc, which can be considered disaccharide hydrolysis product of cellulose.
    • lactose: Gal(β 1,4)Glc, also known as milk sugar. .
    • sucrose: Glc(α 1,2)Fru. Since Fru is attached through the anomeric OH of this ketose, the Fru is not in equilibrium with its straight chain keto form, and hence sucrose is a nonreducing sugar.

    The differences between lactose and sucrose are illustrated in Figure \(\PageIndex{18}\) below. Note that the β-D-fructofuranose ring is flipped (left to right as in turning one of your hands over) compared to Figure \(\PageIndex{16}\) above.

    disacchformation.svg
    Figure \(\PageIndex{18}\): Structures of lactose and fructose

    Acetal links between sugars in glycans can be hydrolyzed by water (catalyzed by H+) just as with the other key biological polymers, proteins and nucleic acids.

    The disaccharide described above that are linked through a 1,4 linkage are called reducing sugars since they can act as reducing agent in a process when they themselves get oxidized. For example, in lactose, since galactose is attached to glucose through the OH on C4, the anomeric glucose carbon, C1, could revert to the noncyclic aldehyde form. This aldehyde is susceptible to oxidation by reagents (Benedicts Solution - with citrate, Fehling's reagent - with tartrate) as these reagents are subsequently reduced. In both reagents, reducing sugars reduce a basic blue solution of CuSO4 (Cu2+) to a brick red precipitate of \(\ce{Cu2O}\) (Cu+). Sugars (monosaccharides, disaccharides and polysaccharides) which can form an aldehyde at C1 or have an α-hydroxymethyl ketone group which can isomerize to an aldehyde under basic conditions (such as fructose) are called reducing sugars. These oxidizing agent are mild and react with aldehydes and not ketones.

    If a monosaccharide, disaccharide or even polysaccharide as a least one hemiacetal or hemiketal link (for instance the second sugar in lactose), it is a reducing sugar, as the monomer with the cyclic hemiacetal can reversibly open to form an aldehyde. However if the only links in sugars are full acetals (such as in sucrose when the link is between the two anomeric carbons), the sugar is not reducing.


    This page titled 7.1: Monosaccharides and Disaccharides is shared under a not declared license and was authored, remixed, and/or curated by Henry Jakubowski and Patricia Flatt.