Carbohydrates (Sugars): Comprehensive Study Notes

Definition & General Formula

  • Carbohydrates are polyhydroxy aldehydes or ketones.
  • Empirical formula: (C\cdot H2O)n with n\ge 3 ("carbon + water").

Classification of Carbohydrates

  • Monosaccharides: single‐unit sugars; sweet; freely water-soluble.
  • Oligosaccharides: short (typically 2–10) covalently linked monosaccharides.
  • Polysaccharides: long chains (hundreds–thousands) of monosaccharides.
  • “Saccharide” derives from Latin "sacchararum" (sweet taste of mono/di-sugars).

Chirality & Stereochemistry

  • All monosaccharides except dihydroxyacetone are chiral.
  • Fischer D/L system uses glyceraldehyde as reference.
    • D-glyceraldehyde: OH on right; dextrorotatory.
    • L-glyceraldehyde: OH on left; laevorotatory.
  • Most natural carbohydrates are D, but L forms exist.
  • Recognition rules:
    • In Fischer projection, OH on highest-numbered chiral C → right = D, left = L.
    • Mirror images are enantiomers; other stereoisomers are diastereomers.

Important D-Aldoses (memorize)

  • D-Glyceraldehyde, D-Ribose, D-Arabinose, D-Xylose, D-Glucose (blood sugar), D-Mannose, D-Galactose, D-Idose.
  • Biological notes:
    • D-Ribose/D-deoxyribose → nucleic acids.
    • D-Glucose → universal metabolic fuel; part of lactose, starch, cellulose, glycogen.
    • D-Mannose → plant polysaccharides.
  • Mnemonics:
    • “Aldose R/L pattern” (memory aid only, not for drawing).
    • “Man with finger-gun” to recall D-mannose configuration.

Epimers

  • Epimers: diastereomers differing at a single stereogenic C.
    • D-Mannose is the C-2 epimer of D-Glucose.
    • D-Galactose is the C-4 epimer of D-Glucose.

D-Ketoses

  • Carbonyl at C2; one fewer chiral center than corresponding aldose.
  • Key examples: D-Dihydroxyacetone (achiral), D-Ribulose, D-Xylulose, D-Fructose (fruit sugar).

Organic Chemistry Interlude I – Reversible Hemiacetal/Hemiketal Formation

  • Aldehyde + alcohol ⇌ hemiacetal:
    \text{R-CHO}+\text{R'-OH}\rightleftharpoons\text{R-CH(OH)-OR'}
  • Ketone + alcohol ⇌ hemiketal:
    \text{R-CO-R''}+\text{R'-OH}\rightleftharpoons\text{R-C(OH)(OR')-R''}

Cyclization of Monosaccharides

  • For D-series, highest-numbered C drawn "up" in Haworth; L drawn down.
  • Glucose mostly forms six-membered pyranose rings.
    • α-D-glucopyranose: anomeric OH down (axial); <1 % of chair population.
    • β-D-glucopyranose: anomeric OH up (equatorial); ≈64 % (thermodynamic favorite).
  • Fructose primarily forms five-membered furanose rings (α/β analogues).
  • Other minor tautomers (glucofuranose, fructopyranose) coexist in solution.

Anomers & Mutarotation

  • Ring formation creates new stereocenter (anomeric C): α vs β anomers.
  • Interconversion in solution via open-chain form = mutarotation.
  • Equilibrium composition is sugar-specific; β-D-glucopyranose predominates.

Modified Monosaccharides

  • Amino sugars: replace C-2′ OH with NH_2 (e.g., β-D-glucosamine); acetylation → N-acetylglucosamine (GlcNAc).
  • Deoxy sugars: replace OH with H (e.g., 2′-deoxy-D-ribose in DNA).

Organic Chemistry Interlude II – Irreversible Acetal/Ketal Formation

  • Hemiacetal + alcohol → acetal + H_2O.
  • Hemiketal + alcohol → ketal + H_2O.
  • In sugars, this condensation yields O-glycosidic (acetal) linkages.

Glycosidic Linkage Nomenclature

  • Format: \alpha/\beta\text{-(anomeric C# first)}\rightarrow\text{(C# of second)}.
  • Example: Maltose = \alpha 1\rightarrow4 linkage between two glucoses.

Disaccharides

  • Maltose (malt sugar)
    • Glc α(1→4)Glc; reducing; product of starch hydrolysis; enzyme: maltase.
  • Cellobiose
    • Glc β(1→4)Glc; reducing; cellulose dimer; enzyme: cellulase.
  • Lactose (milk sugar)
    • Gal β(1→4)Glc; reducing; major energy source in milk; enzyme: lactase.
  • Sucrose (table sugar)
    • Glc α(1→2)β Fru; non-reducing (both anomeric Cs bonded); enzyme: sucrase/invertase.
  • Anomeric configuration (α vs β) dictates 3-D shape and enzyme specificity.

Lactose Intolerance (Clinical Connection)

  • Normal: lactase hydrolyzes lactose → glucose + galactose (absorbed).
  • Deficiency → undigested lactose reaches colon ⇒ bacterial fermentation ⇒ CO2, H2, lactic/acetic acids.
  • Symptoms: bloating, flatulence, abdominal pain, osmotic diarrhea.
  • Management: dietary lactose restriction, lactase supplements, fermented dairy.

Physical & Chemical Properties of Mono/Disaccharides

  • Sweet taste; solids at room temp.
  • Extensive hydrogen-bonding → high water solubility; concentrated solutions very viscous (e.g., honey >80 % carbs, mostly D-fructose + D-glucose).
  • Reducing sugars possess free hemiacetal/hemiketal and react with mild oxidants (Benedict’s, Fehling’s) and participate in Maillard browning.

Key Numerical Facts

  • Empirical formula: (C\cdot H2O)n, n\ge 3.
  • β-D-glucopyranose ≈64 % in aqueous equilibrium; α form <1 % in axial chair (≈36 % including other chairs).

Practical & Philosophical Notes

  • Stereochemistry dictates biological function; enzymes highly selective for one anomer/epimer.
  • Homochirality (dominance of D-sugars) is a foundational principle of biochemistry.
  • Industrial/biotech relevance: fermentation (maltose), biofuels (cellulose → cellobiose), dairy processing (lactose), sweetener production (sucrose inversion).

Study Mnemonics Recap

  • Aldose R/L string mnemonics aid Fischer reconstruction.
  • “Man with finger-gun” = D-mannose (C2 & C3 OH left).
  • “Man at two, Gal at four” for epimer positions relative to glucose.
  • Pyran = six-membered ring; furan = five-membered.