Structure and Function of Carbohydrates

Objectives

  • Describe structural features & biological functions of all major classes of carbohydrates.
  • Relate the open-chain structure of D-glucose\text{D-glucose} to other monosaccharides.
  • Detail the chemical reactions typical of monosaccharides (oxidation–reduction, esterification, amino-substitution, glycoside formation).
  • Explain the nature of the glycosidic bond & describe common disaccharides.
  • Differentiate the types of polysaccharides (storage, structural, bacterial).
  • Outline normal digestion of dietary carbohydrate & recognize clinical problems that arise when disaccharide degradation is impaired (e.g.
    lactose intolerance, galactosemia).

Reference Texts Mentioned

  • Harper’s Illustrated Biochemistry (28th ed.)
  • Lippincott Illustrated Reviews: Biochemistry (7th ed.)
  • Devlin: Textbook of Biochemistry with Clinical Correlations

Fundamental Definition & Formula

  • “Carbohydrate” = hydrate of carbon → composed of C, H, O.
  • General empirical formula: C<em>n(H</em>2O)nC<em>n(H</em>2O)_n.
  • Contain an aldehyde (aldose) or ketone (ketose) carbonyl.
  • Classification criteria:
    • Length of carbon chain.
    • Number of sugar units.
    • Position of the carbonyl (C=O).
    • Stereochemistry (D / L; α / β).

Classification by Number of Sugar Units

  • Monosaccharides – single residue.
  • Disaccharides – 2 residues.
  • Oligosaccharides – 3–10 residues.
  • Polysaccharides – >10 (often hundreds–thousands).
  • Residues are connected via O-glycosidic bonds.

Core Monosaccharide Skeletons

  • Smallest useful template drawn: D-glyceraldehyde (aldotriose) & dihydroxyacetone (ketotriose).
  • Nomenclature by carbon count: triose, tetrose, pentose, hexose, etc. Either aldehydic or ketonic.

Representative Linear Examples

  • Aldotriose: D-glyceraldehyde\text{D-glyceraldehyde}.
  • Ketohexose: D-fructose\text{D-fructose}.
  • Aldopentose: D-ribose\text{D-ribose}.
  • Aldohexoses: D-glucose\text{D-glucose}, D-galactose\text{D-galactose}, D-mannose\text{D-mannose}.

Stereochemistry Essentials

  • Stereoisomers have identical bonding sequence but different 3-D orientation → distinct physical & biochemical behaviour.
  • Enantiomers = non-superimposable mirror images (designated D or L by Fischer projection relative to the chiral centre farthest from C=O).
  • Life uses almost exclusively D-sugars & L-amino acids.

Physical property: Optical rotation

  • Dextrorotatory (+) often corresponds to D-form; levorotatory (–) to L-form, but this is not a strict rule – sign is experimental.

Fischer vs. Haworth vs. Perspective

  • Fischer projection: vertical bonds project behind plane; horizontal come out toward viewer.
  • Haworth: cyclic form shown as planar ring; orientation of substituents “up” (β) or “down” (α) relative to ring plane.

Important Physiologic Monosaccharides

• D-Glucose

  • Aldohexose; synonyms: dextrose, grape sugar, “blood sugar”.
  • Most abundant organic molecule; circulating level ≈ 0.1 % w/v.

• D-Fructose

  • Ketohexose; sweetest natural sugar; predominant in fruit & sucrose.

• D-Galactose

  • Constituent of lactose; must be converted to glucose for metabolism.

• D-Ribose / 2-Deoxyribose

  • Pentoses used for RNA & DNA backbone; little role in energy.

Intramolecular Cyclization & Anomerism

  • Aldoses form hemiacetals; ketoses form hemiketals when distal OH attacks C=O.
  • Generates a new stereocentre (anomeric carbon).
    • α-anomer: freshly formed OH points down (opposite side from CH$2$OH in D-sugars). • β-anomer: OH points up (same side as CH$2$OH in D-sugars).
  • α ⇌ β equilibrium in solution = mutarotation.

Typical Reactions of Monosaccharides

  1. Oxidation–Reduction
    • Aldehyde group can reduce Cu2+^{2+} in Benedict’s, Fehling’s or Ag+^{+} in Tollens’ reagent → diagnostic for “reducing sugars.”
    • Simplified Benedict equation:
      <br/>R-CHO+2 Cu2++5 OH−amp;→R-COO−+2 Cu<em>2O↓+3 H</em>2O<br/>\begin{aligned}<br /> \text{R-CHO} + 2\,Cu^{2+} + 5\,OH^- &amp;\rightarrow \text{R-COO}^- + 2\,Cu<em>2O \downarrow + 3\,H</em>2O<br /> \end{aligned}
    • Urinalysis for glucosuria.
  2. Enediol rearrangement under mild base interconverts glucose ↔ fructose via enediol intermediate.
  3. Esterification
    • Hydroxyls react with acids; physiologically most important are phosphate esters.
    • Example (hexokinase):
      D-glucose+ATP→kinaseD-glucose-6-P+ADP\text{D-glucose} + \text{ATP} \xrightarrow{\text{kinase}} \text{D-glucose-6-P} + \text{ADP}
  4. Amination ⇒ Amino sugars
    • Replace OH by NH2NH_2 → glucosamine, galactosamine etc.
    • Roles: bacterial peptidoglycan, chitin, cartilage (chondroitin sulfate), glycoproteins, glycolipids.
  5. Glycosidic bond formation
    • Condensation of anomeric OH with another OH (of sugar, protein, lipid) → O-glycoside; configuration (α or β) locked.

Nomenclature of Glycosidic Linkages

General description: α(1→4)\alpha(1\to4) etc., where
• Symbol (α / β) describes configuration at anomeric carbon of first residue.
• Numbers indicate the linked carbons.
• Second residue’s anomeric carbon may be free (reducing end) or involved (non-reducing disaccharide).

Common Disaccharides

• Maltose (malt sugar)

  • α-D-Glc\alpha\text{-D-Glc}-(1→4)-D-Glc\text{D-Glc}.
  • Found in germinating grains, brewing; hydrolysed by maltase.
    • Cellobiose
  • β-D-Glc\beta\text{-D-Glc}-(1→4)-D-Glc\text{D-Glc}.
  • Intermediate of cellulose breakdown; humans lack β-(1→4)-glucosidase.
    • Lactose (milk sugar)
  • β-D-Gal\beta\text{-D-Gal}-(1→4)-D-Glc\text{D-Glc}.
  • Hydrolysis by lactase; deficiency → lactose intolerance (GI gas, cramps).
  • Failure of galactose metabolism enzymes → galactosemia (galactose + galactitol accumulation → cataracts, retardation, fatality).
    • Sucrose (table sugar)
  • α-D-Glc\alpha\text{-D-Glc}-(1→2)-β-D-Fru\beta\text{-D-Fru}.
  • Non-reducing (both anomeric carbons tied up).

Relative Sweetness (sucrose = 1.00)
• Lactose 0.16 • Galactose 0.32 • Maltose 0.33 • Fructose 1.73
• Artificial: aspartame ≈180; saccharin ≈450.

Polysaccharides

Storage
• Starch (plants)
– Amylose: unbranched α(1→4)\alpha(1→4) coils, ≤ 4000 residues.
– Amylopectin: α(1→4)\alpha(1→4) backbone with α(1→6)\alpha(1→6) branch every 24–30 residues.
• Glycogen (animals)
– Similar to amylopectin but branches every 8–12 residues; stored as cytoplasmic granules in liver & muscle.

Structural
• Cellulose
– Linear β-(1→4)-glucan; extensive H-bonding → rigid fibres → plant cell walls.
– Indigestible by humans; dietary “insoluble fibre.”
• Mucopolysaccharides (Glycosaminoglycans)
– e.g. hyaluronic acid: repeating β(1→3)\beta(1→3) N-acetyl-glucosamine – β(1→4)\beta(1→4) D-glucuronic acid.
– Viscous ECM lubricant, joint fluid, eye vitreous.
• Peptidoglycans
– Bacterial cell wall: alternating N-acetyl-glucosamine & N-acetyl-muramic acid linked β-(1→4) with peptide cross-bridges (species-specific, e.g.
Staphylococcus aureus).

Glycoproteins

  • Proteins covalently bound to 1–30 % carbohydrate.
  • Functions: immunologic shielding (antibodies), cell–cell recognition, blood clotting factors, host–pathogen adhesion.
  • Common sugar components: glucose, mannose, galactose, fructose, sialic acid, NN-acetyl-galactosamine, NN-acetyl-glucosamine.
  • Linkages:
    • O-linked: Ser/Thr hydroxyl.
    • N-linked: Asn amide N–H\text{N}–\text{H}.

Digestion & Clinical Correlates (implicit from slides)

  • Dietary polysaccharides (starch, glycogen) → maltose / isomaltose by amylase → glucose by maltase/isomaltase.
  • Lactose → glucose + galactose via lactase.
  • Sucrose → glucose + fructose via sucrase (invertase).
  • Enzyme deficiencies → malabsorption (lactose intolerance) or toxic accumulation (galactosemia).

Ethical & Practical Notes

  • Understanding stereochemistry crucial for drug design – enzymes & transporters discriminate D vs L & α vs β.
  • Public-health impact: screening newborns for galactosemia prevents irreversible damage.
  • Lactase persistence/intolerance illustrates gene-culture co-evolution (dairy farming).

Numeric / Statistical Points

  • Blood glucose normal ≈ 0.1 % (≈ 5 mM, 90 mg/dL).
  • Sugar-cane sucrose content ~20 % by weight.

Key Equations & Structures (LaTeX rendered)

  • Empirical carbohydrate formula: C<em>n(H</em>2O)nC<em>n(H</em>2O)_n.
  • Hexokinase: Glc+ATP→Glc-6-P+ADP.\text{Glc} + \text{ATP} \rightarrow \text{Glc-6-P} + \text{ADP}.
  • Benedict reaction (simplified): R-CHO+2Cu2++5OH−→R-COO−+2Cu<em>2O↓+3H</em>2O.\text{R-CHO} + 2Cu^{2+} + 5OH^- \rightarrow \text{R-COO}^- + 2Cu<em>2O\downarrow +3H</em>2O.
  • General glycosidic linkage description: α(1→4),  β(1→6),\alpha(1\to4),\;\beta(1\to6), etc.

Summary Connections

  • Carbohydrate chemistry bridges foundational organic concepts (isomerism, functional groups) with physiology (energy metabolism, structural biology).
  • Alterations in simple disaccharide processing manifest clinically; polymer structures underpin diverse materials from cotton (cellulose) to bacterial cell wall targets of antibiotics.
  • Glycoconjugates extend carbohydrate functionality into information-rich motifs modulating immunity & cell communication.