Carbohydrates and Saccharides

Carbohydrates - Part 1: Saccharides

Introduction to Carbohydrates

  • Carbohydrates are the most abundant macromolecules in nature.
  • Photosynthesis converts over 100 billion metric tons of CO2 and H2O into cellulose and other plant products annually.
  • The term "carbohydrate" generally refers to carbon-containing compounds with hydroxyl, keto, or aldehydic functionalities.
  • Carbohydrates range in size from simple monosaccharides (sugars) to oligosaccharides and polysaccharides.

Role and Definition of Carbohydrates

  • Carbohydrates constitute more than half of all organic molecules.
  • Main roles of carbohydrates in nature:
    • Energy storage
    • Structural support (cellulose)
    • Lipid and protein modification (membranes asymmetry, recognition by IgG/fertilization/virus recognition/cell-cell communication)
  • Definition: Carbohydrates, sugars, and saccharides are polyhydroxy compounds with at least two hydroxyl groups (OH). The general formula is Cn(H2O)_n, representing a hydrate of carbon.
  • Monosaccharides are classified into ketoses and aldoses.
  • The number of carbon atoms is crucial for nomenclature (e.g., triose = 3, pentose = 5, hexose = 6).

Characteristics of Carbohydrates

  • Existence of at least one, often two or more, asymmetric centers.
  • Ability to exist in either linear or ring structures.
  • Capacity to form polymeric structures via glycosidic bonds.
  • Potential to form multiple hydrogen bonds with water or other molecules in their environment.

Naming and Classification of Carbohydrates

  • Carbohydrates derive from the basic molecular formula (CH2O)n where n [( Cx H2O)_n (indicating they are hydrates of carbon).
  • Classified into three groups:
    • (i) Monosaccharides
      • Simple sugars
      • Single polyhydroxyl unit
      • Cannot be hydrolyzed into simpler forms
      • Trioses: smallest monosaccharides, contain three carbon atoms
      • Examples: Tetroses (4C), Pentoses (5C), Hexoses (6C), Heptoses (7C), etc.
      • Disaccharide - two sugars linked together. Can be the same molecule or two different sugars. Attached together via a glycosidic linkage
    • (ii) Oligosaccharides
      • Composed of 2 to 10 simple sugar residues
      • Examples: Disaccharides (common), trisaccharides (occurs frequently)
    • (iii) Polysaccharides
      • Straight or branched long-chain monosaccharides.
      • Bonded together by glycosidic linkages, hundreds to thousands of monosaccharide units.
      • Molecular weight ranges up to 1 million or more.

Classes of Carbohydrates

  • Monosaccharides:
    • Contain a single polyhydroxy aldehyde or ketone unit (e.g., glucose, fructose).
  • Disaccharides:
    • Consist of two monosaccharide units linked by a covalent bond (e.g., sucrose).
  • Oligosaccharides:
    • Contain 3 to 10 monosaccharide units (e.g., raffinose).
  • Polysaccharides:
    • Contain long chains of hundreds or thousands of monosaccharide units, either straight or branched (e.g., cellulose, glycogen, starch).

Classification of Monosaccharides

  • Monosaccharides are classified based on:
    • Placement of the carbonyl group
    • Number of carbon atoms
    • Chiral handedness
  • If the carbonyl group is an aldehyde, it is an aldose.
  • If the carbonyl group is a ketone, it is a ketose.
  • Monosaccharides are named based on the number of carbon atoms: trioses (3C), tetroses (4C), pentoses (5C), hexoses (6C), etc.
  • These two systems are combined (e.g., glucose is an aldohexose - a six-carbon aldehyde).

The Family of D-Aldoses

  • D-Glyceraldehyde is the simplest aldose.
  • Additional stereogenic centers are added below the carbonyl group, generating two additional stereoisomers each time.
  • Examples include D-erythrose, D-threose, D-ribose, D-arabinose, D-xylose, D-lyxose, D-allose, D-altrose, D-glucose, D-mannose, D-gulose, D-idose, D-galactose, and D-talose.

Ketoses

  • Examples of ketoses and their structures:
    • Ketotriose: dihydroxyacetone
    • Ketotetrose: D-erythrulose
    • Ketopentoses: D-xylulose, D-ribulose
    • Ketohexoses: D-psicose, D-fructose, D-sorbose, D-tagatose

Carbonyl Group

  • A carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O.
  • The term can also refer to carbon monoxide as a ligand in inorganic or organometallic complexes.

Functional Groups: Aldehyde and Ketone

  • Aldehyde:
    • Carbon atom bonded to a hydrogen atom and double-bonded to an oxygen atom.
    • Polar due to oxygen's higher electronegativity, creating electron deficiency at the carbon atom.
  • Ketone:
    • Characterized by a carbonyl group (O=C) linked to two other carbon atoms.
    • Distinguished from carboxylic acids, aldehydes, esters, amides, and other oxygen-containing compounds by the carbonyl carbon bonded to two carbon atoms.

Aldose and Ketose Structures

  • An aldose contains an aldehyde group.
  • A ketose contains a ketone bonding pattern.
  • General forms:
    • Aldose: HO-C-(C-OH)_x-C-H where x = 1 to 5
    • Ketose: HO-C-(C-OH)_x-C-C-H where x = 0 to 4

Number of Carbons in Monosaccharides

  • Monosaccharides are classified by the number of carbon atoms they contain.
    • 3 Carbons: Triose
    • 4 Carbons: Tetrose
    • 5 Carbons: Pentose
    • 6 Carbons: Hexose
    • 7 Carbons: Heptose
  • Monosaccharides are also classified by the number of carbons and whether they are aldoses or ketoses.
    • Using the prefix "aldo" or "keto" before "triose," "tetrose," "pentose," "hexose," or "heptose."
    • Example: An aldose with five carbons is an aldopentose.

Stereochemistry of Carbohydrates

Two Forms of Glyceraldehyde

  • Glyceraldehyde, the simplest carbohydrate, exists in two isomeric forms that are mirror images of each other.
  • These forms are stereoisomers (enantiomers).

Stereoisomers and Enantiomers

  • Glyceraldehyde is a chiral molecule, meaning it cannot be superimposed on its mirror image.
  • The two mirror-image forms of glyceraldehyde are enantiomers of each other.
  • Molecules with just one chiral carbon have a pair of geometric isomers called enantiomers.

Chirality and Handedness

  • Chiral molecules have the same relationship to each other that left and right hands have when reflected in a mirror.

Van't Hoff’s Rule and Stereoisomers

  • Optically active molecules are designated as D or L according to the furthest asymmetric carbon from the ketone or aldehyde.
  • Optical activity is independent of D or L designation (e.g., D(-) fructose).
  • Increase in the number of carbons increases possible stereoisomers.
    • Van't Hoff’s Rule: A compound with n asymmetric C atoms has a maximum of 2^n possible stereoisomers.
  • Enantiomers are stereoisomers that are non-superimposable mirror images (e.g., L and D forms of sugars, D-glyceraldehyde and L-glyceraldehyde).

Multiple Chiral Carbons and Stereoisomers

  • If a molecule has more than one chiral carbon, it will have more than one pair of enantiomers.
  • If a monosaccharide has n chiral carbons, it will have 2^n stereoisomers.
    Example: A molecule with three chiral carbons will have 2^3 = (2 x 2 x 2) = 8 stereoisomers (four pairs of enantiomers).

Physical Properties and Biological Behavior of Stereoisomers

  • Stereoisomers share a molecular and structural formula.
  • Most of the physical properties of these stereoisomers are quite similar; however, the way they each behave in biological systems can be very different.

Three-Dimensional Arrangement of Glyceraldehyde Atoms

  • Glyceraldehyde (smallest monosaccharide) has only one chiral carbon.
  • This results in 2^n = 2^1 = 2 stereoisomers (one pair of enantiomers/nonsuperimposable mirror images).

Fischer Projections

  • For professionals in healthcare, engineering, and science fields to discuss and depict the various monosaccharide stereoisomers, it is necessary to be able to draw two-dimensional (flat) structural formulas on a page or computer display, such that they still contain the three-dimensional information particular to each stereoisomer.
  • As oppose to wedge and dash representations, for monosaccharides, Fischer projections are used for this purpose.

Fischer Projections Orientation

  • In Fischer projections, chiral carbons are implied to be at the intersection of a vertical and horizontal line.
  • Chosen Orientation of a chiral carbon and the four groups that are bonded to it relative to the drawing surface/page in all Fischer Projections is as follows:
    • The bonds from the chiral carbon to the other carbon atoms point at a downward angle, and their shadows form vertical lines on the Fischer projection. These are the bonds from the chiral carbon to groups Y and W.
    • The bonds from the chiral carbon to the non carbon groups point at an upward angle, and their shadows form horizontal lines on the Fischer projection. These are the bonds from the chiral carbon to groups X and Z.
  • For aldoses, the aldehyde group is positioned at the end of the molecule that is closest to the top of the page (position W).
  • For ketoses, the carbonyl carbon is positioned as close as possible to the end molecule that is nearest the top of the page.

Fischer Projections for Glyceraldehyde Stereoisomers

  • The aldehyde group is represented by 'CHO'.
  • Because the other two carbons in glyceraldehyde are not chiral, shorthand notation is used to simplify the Fischer structure.

Fischer Projections for Two Enantiomers of Glyceraldehyde

  • Note that we draw the hydroxyl groups that are on the left-hand side of Fischer projections as “HO.”
  • We do not need to draw the bonds around the top or bottom carbon atoms because they are not chiral.

Drawing Fischer Projections for Multiple Chiral Carbons

  • For monosaccharides with more than one chiral carbon, Fischer projections must be drawn (or interpreted) by considering the orientation around each of the chiral carbons.
  • This is done one chiral carbon at a time.
    Example: Aldotetroses, which contain two chiral carbons.
  • Since aldotetroses each have two chiral carbons, there are 2^2 = (2 x 2) = 4 stereoisomers (two pairs of enantiomers).
    Note: the hydrogen (H) and the hydroxyl group (OH) positions are reversed on chiral carbons for each particular enantiomer pair.

Implication of a Fischer Projection

  • A Fischer Projection is used to deduce the Wedge and Dash Representation.

D- and L- Designations for Monosaccharides

  • Carbohydrates are most often referred to by their common names, which use the “-ose” suffix.
  • A common name is assigned to each pair of enantiomers.
  • To differentiate the two individual monosaccharides of an enantiomer pair, ‘D-’ or ‘L-’ designations are used with the common name.
    • The ‘L-’ designation is used for the enantiomer in which the chiral carbon that is furthest from the top of the Fischer projection has its hydroxyl group on the left.
    • The 'D-' designation is used for the other enantiomer of the pair.
  • D- and L- Sugars nomenclature.

D-Glucose

  • D-glucose is an aldohexose with the formula C6H{12}O6 or (C [\cdot H2O)_6.
  • The red atoms highlight the aldehyde group, the blue atoms highlight the asymmetric center furthest from the aldehyde.
  • -OH is on the right of the Fischer projection, this is a D sugar.

D-Fructose

  • An example of a ketose is fructose.
  • D-Fructose is one of our major dietary carbohydrates.
  • The structure and D vs L form.

Chirality in Monosaccharides

  • Most simple monosaccharides have at least one chiral center.
  • As in the case of amino acids, sugars are given D or L designations based on their similarity with D or L glyceraldehyde.
  • Since some sugars contain many chiral centers, it is necessary to designate one chiral center that will act as the reference.
  • This chiral center is designated as the one that is most distant from the carbon that bears the carbonyl functionality.

Fischer Projections and Carbon Numbering

  • Sugars are often written as Fischer projections, where horizontal bonds project towards you, and vertical bonds project away from you.
  • The numbering of carbons in sugars begins at the end of the chain closest to the carbonyl functionality.

Aldoses

  • If the carbonyl group is an aldehyde, then the sugar is an aldose.
  • Configuration around C2 (red) distinguishes the members of each pair of monosaccharides.
  • Most common aldoses:
    • D-Ribose (Rib)
    • D-Glucose (Glc)
    • D-Mannose (Man)
    • D-Galactose (Gal)
    • D-Xylose (Xyl)
    • D-Arabinose (Ara)
  • All are based on the structure of glyceraldehyde.

Ketoses

  • If the carbonyl group is a ketone, the sugar is a ketose.
  • Configuration around C3 (red) distinguishes the members of each pair of monosaccharides.
  • Most common Ketoses:
    • D-Fructose (Fru)
    • D-Ribulose (Rib)
  • All based on the structure of dihydroxyacetone.

Epimers

  • Epimers are two sugars that differ only in the configuration around one carbon atom of their structures.
  • D-Mannose differs from D-glucose only in its configuration around carbon 2.
  • D-Galactose differs from D-glucose only in its configuration around carbon 4.
  • D-Galactose and D-Mannose are not epimers.

The Cyclic Forms of Monosaccharides

  • Monosaccharides with five to seven carbons can rearrange their bonding pattern to form cyclic structures in aqueous solutions.
  • This reversible reaction interconverts the open-chain form with the cyclic form.
  • The cyclic form is lower in energy, therefore the predominant form.
  • The equilibrium ratio of cyclic to open-chain form is about 100:1.
  • Side view structures of cyclic monosaccharides are called Haworth projections or Haworth structures.
  • The carbon atoms that form the ring are not drawn explicitly, but are implied to occur where lines/bonds meet.

Haworth Projections and Molecular Geometry

  • Each ring-carbon is bonded to two other ring-atoms and two other groups.
  • Groups that are oriented upward relative to the ring-carbons are shaded green.
  • Groups that are oriented downward from ring-carbons are shaded red.

Nobel Prize & Haworth Structures

  • Emil Fisher- Nobel Prize 1891- Organic chemist who found the structure of D glucose
  • Fisher projections - place most oxidized carbon on top
  • Haworth Structures: carbons counted from anomeric C to clockwise from the oxygen in the ring (pyranose) or the #2 C for furanose
  • α form – OH in down position
  • ß form – OH in up position
  • Conformational Structures

α and β Anomers of Glucose

  • Note the position of the hydroxyl group (red or green) on the anomeric carbon relative to the CH_2OH group bound to carbon 5:
    • Either on the opposite sides (α)
    • Or the same side (β).

Hemiacetal Formation

  • A hemiacetal contains both an OR group and OH group bonded to the same carbon.
  • General form of a hemiacetal: R-C(OH)(OR)-R' or H
  • An aldehyde or a ketone will react with an alcohol to form a hemiacetal.
  • aldehyde | ketone + alcohol \rightleftharpoons hemiacetal
  • The OR