TOPICS OF BIOCHEMISTRY
carbohydrates
Simple carbohydrates: monosaccharides. Families of aldoses and ketoses based onD-glyceraldehyde and dihydroxyacetone (respectively). Some important monosaccharides: glucose, fructose and ribose. Cyclic forms of monosaccharides. Glucopyranose Formation. Glycosidic Bonds and Disaccharides. Complex carbohydrates, glycogen and cellulose. glycobiology.
Carbohydrates comprise one of the four major classes of biomolecules (along with proteins, nucleic acids, and lipids. Carbohydrates are aptly named because their general elemental composition is represented by the formula (CH2Ö)n. More specifically, carbohydrates are or are based on polyhydroxy aldehydes or ketones. The simplest carbohydrates are thoseMonosaccharide, such asGlucose fructose, andRibose. The more complex forms - disaccharides and polysaccharides - are constructed as polymers of monosaccharides. table sugar orSucroseis a disaccharide of glucose and fructose. Complex carbohydrates includeGlycogen, a branched polymer of glucose units that is a storage form of carbohydrate in animals, andcellulose, a linear polymer of glucose units found in plant cell walls.
Carbohydrates are the prime example of metabolic "fuel" for cells. The gradual degradation of the monosaccharide glucose is an almost universal pathway (cfGlycolysis), which provides biochemical energy in the form ofAdenosintriphosphat(ATP). Plants, when performing photosynthesis, harvest the energy from sunlight by using it to convert carbon dioxide and carbon dioxidewaterinto carbohydrates and oxygen. The so-called "dark" reactions of photosynthesis, known as theCalvin cycle, are responsible for the uptake of carbon dioxide and its assimilation into carbohydrates.
Monosaccharide
Because carbohydrates are aldehydes or ketones with two or more hydroxyl groups, the simplest monosaccharides are the three-carbon compoundsGlycerinaldehydandDihydroxyaceton(DHA) shown in the figure below. Simple carbohydrates with an aldehyde functional group are mentionedAldosen, while those with functional ketone groups are mentionedKetosis. Glyceraldehyde is thus the simplest aldose and dihydroxyacetone is the simplest ketose.
The middle carbon atom (C2) of glyceraldehyde is chiral because four different groups are attached to it. Therefore, there are two enantiomeric (mirror image) forms of glyceraldehyde,D-Glyceraldehyde andL-glyceraldehyde, both of which are shown. (The term "enantiomer" is equivalent to "stereoisomer".) Fischer projections (explained below) are shown for both stereoisomers. In the case of DHA, the middle carbon corresponds to the carbonyl group.D-Glycerinaldehyd,L-Glyceraldehyde and dihydroxyacetone are structural isomers as both have the chemical formula C3H6Ö3.
Note that the Fischer projections imply a stereochemical convention, as indicated by the side-by-side structural formulas above for bothDandLConfigurations of glyceraldehyde. At any given chiral carbon, the horizontal bonds are taken to project out of the plane of the figure, while vertical bonds recede behind the plane. We will use Fischer projections to represent the larger sugar families (4, 5 and 6 carbon) based on D-glyceraldehyde and DHA.
Both the hydroxyl and carbonyl groups are polar and can participate in hydrogen bonding (however, a carbonyl group can only act as an acceptor). Consequently, carbohydrates are hydrophilic in character. It is worth noting that many of the properties of carbohydrates are related to the reactive nature of the carbonyl group, which is common to both aldoses and ketoses.
D-Glyceraldehyde and DHA can be viewed as the parent compounds of a series of higher carbon atom monosaccharides. Larger monosaccharides are based onD-Glyceraldehyde can be built by inserting additional CH(OH) groups between the aldehyde group (its carbon atom is always denoted as C1 and is shown inblau) and the chiral group with theDConfiguration like C2 fromD-Glyceraldehyde. This group is always considered the one furthest from C1 (always displayed inrotin the figure below).
The addition of the first CH(OH) group creates two possible onesTetrosen(Monosaccharides with four carbon atoms) from the parentD-Glyceraldehyde (a triose) as the added group creates a new chiral center. Note that these tetroses,D-erythrosis andD-threose, are not mirror images of each other, but diastereomers. (Also note the similarity ofD- Threose zur AminosäureThreonin, where C2 of the tetrose corresponds to the alpha carbon of the amino acid.) Another terminological point that arises when comparing the two tetroses. Monosaccharides that differ in configuration at a single chiral carbon are known asEpimere. Hence,D-erythrosis andD-three of them are epimers, differing only in the configuration at C2.
Addition of another CH(OH) group leads to four possible diastereomeric pentoses based onD-Glyceraldehyde. The next addition of CH(OH) generates the series of eight diastereomeric hexoses based onD-Glycerinaldehyd.
The aldoses most commonly encountered in metabolic research are D-glyceraldehyde and its phosphorylated derivatives as wellD-Glucose and derivatives thereof. Ribose and the related deoxyribose are integral parts of nucleotides and nucleic acid structures. Mannose and galactose also play relatively important roles in biochemistry, but other members of this aldose family are rarely encountered.
The ketoses family is based onDihydroxyaceton(DHA). Adding an extra H-C-OH group to DHA gives a four-carbon ketose called erythulose.
This additional group confers a chiral center, hence erythulose exists in two enantiomeric forms,D- andL-. Note that the configuration at C3 is fromD-Erythulose corresponds to that of C2 inD-Glyceraldehyde. Each subsequent addition of a CH(OH) group to monosaccharides with an additional carbon atom creates an additional chiral center, just as it does in the series of aldoses based onD-Glyceraldehyde. Since DHA does not contain a chiral center, there is one less chiral center in the ketoses for the same number of carbon atoms compared to the members of the aldose family. Again, the linear plots of ketoses shown are Fischer projections.
There are two derived ketopentosesD-erythulose,D-Ribulose uD-xulose. These in turn are the basis for two ketohexoses.D-Psychose uD-Fructosebased onD-Ribulose.D-Sorbose andD-tagatose based onD- decide on.
DHA,D-erythulose,D-Ribulose uD-xyulose are all biologically relevant. The only important member of the four ketohexoses isD-Fructose.
Cyclic forms of monosaccharides
Pentoses and hexoses typically assume cyclic forms when the open-chain forms isomerize to intramolecular hemiacetals or hemiketals.
An aldehyde and an alcohol can react to form a hemiacetal. Note the similarity to tetrahedral intermediates we have encountered in reactions of carboxylic acid derivatives such as amides and esters. The tendency for this reaction to occur in a six-carbon aldose is greater because the hydroxyl and aldehyde functional groups are contained within the same molecule and the intramolecular reaction can generate a relatively stable six-membered ring. The analogous process occurs in ketoses—the intramolecular hemiketal formation results in a five- or six-membered ring.
formation of glucopyranose
Cyclization of the open-chain form ofD-Glucose by intramolecular hemiacetal formation gives aD-Glucopyranose molecule.
The cyclization creates an additional chiral center at C1, hence there are two forms ofD-Glucopyranose referred to as α and β (alpha and beta). These alternative forms are calledHe grows up, and C1 here is the anomeric carbon. Note that the anomers can easily be interconverted by inversion to the open chain form and recycling to the other anomer. The representations of the cyclic shapes are known as Haworth projections. The thick bindings of the bottom of the ring are meant to suggest the "plane" of the ring protruding toward the viewer, with the bottom of the ring being closest.
A disadvantage of the Fischer and Haworth projections is that they do not explicitly show the actual conformation(s) or position of all the atoms of the sugar molecule in three-dimensional space. More stereochemically realistic representations of the conformations of the furanose and pyranose rings, which are common in biochemistry, are conveyed through drawings of "shell", "chair" and "boat" shapes, as shown below.
The pentoses ribose and deoxyribose form intramolecular hemiacetals. These furanose rings make up most of the backbone structure of nucleic acids. For glucose, the chair conformation is the most common pyranose ring conformation, as for β-D-Glucopyranose (bottom left). In all these cases there is no "level" of the ring - the ring is curled. There are two types of positions for ring substituents: equatorial and axial. The former point further away from the ring and are less sterically constrained. The latter pointing up or down in the figure, are closer to the mass of the ring and are therefore in "tighter" positions. This is most evident with the chair.
There are many possible conformations for furanose and pyranose rings, but the most stable conformation for a given sugar depends on the configuration of its chiral carbon atoms and whether modified substituents are present. (For example, one or more hydroxyl groups could be involved in ether linkages with another alcoholic (hydroxyl) group or an ester linkage with a phosphate group.) Chair conformations tend to be dominant for most pyranose rings because steric repulsion is usually minimized. Interestingly e.gD-Glucose, all the bulkier substituents of the ring (OH groups and the C6 substituent) can occupy equatorial positions in a chair form of a pyranose ring when the anomeric carbon is in the β configuration.
Glycosidic Bonds and Disaccharides
The more complex carbohydrate forms are built as polymers of monosaccharides. Fundamental to the way simple sugars can polymerize is the glycosidic bond. In principle, any of the hydroxyl groups could form, for example, ether or ester linkages. However, when the hydroxyl group attached to the anomeric carbon condenses with another alcohol, converting the hemiacetal to an acetal, the bond created is referred to as aglycosidic bond, or (especially for this case) onÖ-glycosidic bond. If the reaction occurs with an amineN-glycosidic bond is formed.
Upon formation of a glycosidic bond, mutarotation is blocked in the glycosyl residue since its anomeric carbon is derivatized. This also protects the monosaccharide moiety from oxidation by copper ions under basic conditions (Fehling test), i.e. the sugar moietyNot reducing.
table sugar orSucroseis a disaccharide of glucose and fructose. Note that the glycosidic bond connects the anomeric carbon atomsbothSugar units, therefore sucrose is non-reducing. Other common disaccharides are maltose andLactose.
Phosphorylated forms of monosaccharides are of paramount importance in biochemistry. A glycosyl phosphate ester is a somewhat activated target for a nucleophilic substitution reaction (glycosyl transfer). An example isGlucose-1-phosphat.
Complex carbohydrates
Complex carbohydrates includeGlycogen,a branched polymer of glucose units which is a storage form of carbohydrate in animals, andcellulose, a linear polymer of glucose units found in plant cell walls.AmyloseandAmylopektinare two forms of starch, polymers of glucose.
Glycobiology
Glycobiology is a relatively new branch of molecular and cell biology that focuses on the role of oligosaccharides (or glycans) as essential biochemical and structural components of eukaryotic cells. For the most part, glycans are attached to macromolecules on the surface of cells, forming a dense layer called theGlycocalyx. Cell surface glycoproteins play important mediating roles in cell-matrix and cell-cell interactions. These roles are further elaborated in the context of complex multicellular organisms, where glycans are involved in tissue and organ development and structure, and are involved in molecular mechanisms of pathogenesis, such as those that occur when a parasite gains access to a host .
The types of monosaccharide units common in animal glycans are sialic acids, hexoses, hexosamines, deoxyhexoses, pentoses, and uronic acids (Ref. 2, §64). The termGlycoconjugateis used to refer generally to glycans or oligosaccharides attached to another class of biological molecules, forming glycolipids and glycoproteins.
For more information on glycobiology see Chapter 11 of Ref 1 starting at the bottom of p312 and Ref 2 for a more comprehensive view.
Pages on related topics:
- Protein
- nucleic acids
- LIPID
- Glycolysis- Metabolism of glucose
- water