Biochemistry: Monosaccharides and Chirality

Monosaccharides

• Classified by number of carbons (triose, tetrose, pentose, hexose) and carbonyl group type (aldose or ketose)
• Two trioses exist, each with two hydroxyl groups and one carbonyl group
• Glyceraldehyde, the simplest D-aldose, has one chiral carbon and exists in two enantiomeric forms

Chirality in Monosaccharides

• Glyceraldehyde is used as a reference for describing carbohydrate structure
• D-monosaccharides have the same conformation around the chiral carbon farthest from the aldehyde or ketone group as D-glyceraldehyde
• D and L symbols indicate structural similarity to D-glyceraldehyde, not optical rotation
• D and L refer to the stereochemistry at the highest numbered chiral carbon

Epimers

• Pairs of monosaccharides that differ only in configuration at one carbon
• D-ribulose and D-xylulose are epimers, differing at C-3

L-Sugars

• Mirror images of corresponding D sugars
• Conformation at all chiral carbons is reversed

Cyclic Hemiacetal Structures of Monosaccharides

• Monosaccharides exist in cyclic hemiacetal form where the carbonyl carbon forms an ether group and a hydroxyl group
• Hemiacetal formation involves the reaction of an alcohol with an aldehyde or ketone
• For aldohexoses, C-5 hydroxyl group reacts with the aldehyde carbon
• This is an equilibrium reaction favoring the ring form

Conventions for Writing Monosaccharide Structures

• Fischer structures can be adapted to show cyclic structures
• Haworth formulas use planar hexagons to represent cyclic structures
• Ring oxygen is on the top right
• Methylol group (CH2OH) is up for D sugars and down for L sugars
• For D sugars, groups on the left of the Fischer structure are "up" in Haworth, and groups on the right are "down"
• Ring is numbered clockwise, starting from the carbon adjacent to the oxygen
• Hydrogen atoms are usually not shown
• For L sugars, the methylol group is "down"
• To convert a Haworth structure to a chair structure, "up" groups are above the equatorial plane, and "down" groups are below
• The CH2OH group is generally equatorial

Monosaccharide Anomers

• Stereochemistry at carbons 2, 3, 4, and 5 is fixed in a given aldohexose
• Two possible conformations of the newly formed hydroxyl group when C-5 hydroxyl reacts with carbonyl carbon:
  • α: hydroxyl group opposite to the CH2OH group ("down")
  • β: hydroxyl group in the same orientation as the CH2OH group ("up")
• β form of D-glucose is most stable due to equatorial positions of CH2OH and OH groups
• These two diastereomers are called anomers
• The carbonyl carbon that reacts to form the hemiacetal is the anomeric carbon
• Anomers can be isolated and have different chemical and physical properties
• Mutarotation is the interconversion between α and β isomers in solution
• α-D-glucose has a specific rotation of +112°, while the β form has +19°
• A freshly prepared solution of α-D-glucose has a specific rotation of 112°, but decreases to 52° at equilibrium
• For β-D-glucose, the specific rotation increases from 19° to 52° at equilibrium

Oxidation Reactions of Monosaccharides

• Strong Oxidising Agents: convert aldehyde group and terminal alcohol group to carboxylate groups
• Diacids: formed from hexoses, called aldaric acids
  • Examples:
    • Bromine Water (Br2 / H2O) - colorless solution
    • Tollens Reagent (Ag+ as Ag[NH3]2+) - colorless solution, forms silver mirror
    • Benedict’s or Fehling’s Reagent (Cu2+) - blue solution, forms brick-red precipitate
• Reducing Sugars: carbohydrates that reduce Cu(II) to Cu(I) or Ag(I) to Ag metal
• Non-reducing Sugars: do not reduce these reagents
• Reducing sugars contain an aldehyde group or an α-hydroxyketone
• Under basic conditions, α-hydroxyketones are in equilibrium with the aldehyde form

Reduction Reactions of Monosaccharides

• The carbonyl group of a monosaccharide can be reduced to an alcohol using reducing agents like NaBH4 and hydrogen with a catalyst

Formation of Osazones

• Aldoses react with phenylhydrazine (Ph–NH–NH2) to form phenylhydrazones
• With excess phenylhydrazine, osazones are formed
• Osazones are crystalline derivatives with sharp melting points, used for identifying unknown sugars
• Osazone formation destroys stereochemistry at C-2
• Compounds differing only at C-2 give the same osazone
• C-2 ketoses also give osazones
• D-glucose, D-mannose, and D-fructose all give the same osazone

Formation of Glycosides (Acetals)

• Monosaccharides in the hemiacetal form react with an alcohol to form acetals
• Only the anomeric -OH group is replaced by the -OR group
• Glycosides are stable in water and aqueous base, but hydrolysed in aqueous acid
• Glycosides are widespread in nature
• Glycosides can be hydrolysed enzymatically by emulsin (β linkages) and maltase (α linkages)

Disaccharides

• Carbohydrates containing two monosaccharide units joined by a glycoside bond
• Examples:
  • Maltose: found in germinating grains, corn syrup, and obtained from starch hydrolysis
    • Two D-glucose units joined by α-1,4-glycoside bond
    • Reducing sugar, can be hydrolysed by maltase
  • Cellobiose: obtained from cellulose hydrolysis
    • Identical to maltose but with β-1,4-linkage
    • Can be hydrolysed by emulsin
  • Lactose: found in mammalian milk
    • D-galactose and D-glucose units joined by β-1,4-linkage
    • Reducing sugar due to free hemiacetal system
  • Sucrose: table sugar from sugar cane
    • Glucose and fructose units joined by α-1,2-glycoside bond
    • Non-reducing sugar due to absence of free anomeric carbons
    • Hydrolysis forms 50:50 mixture of glucose and fructose called invert sugar

Polysaccharides

• Polymers of monosaccharides
• Examples:
  • Starch: reserve carbohydrate for plants
    • Two main types: amylose and amylopectin
    • Both are polymers of α-glucose
    • Amylose: linear, unbranched chains of up to 4000 D-glucose monomers joined by α-1,4-glycoside bonds
    • Amylopectin: highly branched structure with 24-30 monomer units joined by α-1,4- and α-1,6-glycoside bonds
  • Glycogen: reserve carbohydrate for animals
    • Highly branched chains of D-glucose joined by α-1,4- and α-1,6-glycoside bonds
    • Lower molecular weight and more highly branched than amylopectin
  • Cellulose: major component of plant cell walls, also in cotton
    • Linear polymer of D-glucose joined by β-1,4-glycoside bonds
    • Humans lack β-glycosidases and cannot digest cellulose
    • Strong material due to hydrogen bonding between chains

Modified Sugars

• Deoxy sugars and amino sugars found in natural and synthetic compounds

Kanosamine

• 3-amino-3-deoxy-D-glucose
• Produced by Bacillus cereus UW85, a Gram-positive bacterium

Neuraminic acid

• 5-amino-3,5-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid
• Nine-carbon monosaccharide, amino derivative of a ketononose (nine-carbon keto sugar)