Unit 1: Acid-Base Chemistry and Carbohydrates

I. Orientation

Biochemistry depends on how water, acids, bases, and carbon compounds behave in aqueous cells. Acid–base equilibria determine enzyme activity, protein charge, membrane transport, and blood pH, while carbohydrates provide energy, structural material, and cell-recognition signals.

• Governing principle: Proton transfer and reversible chemical equilibrium control acid–base behavior; covalent structure and stereochemistry control carbohydrate properties.
• Important convention: pH is logarithmic, so a change of one pH unit represents a tenfold change in hydrogen-ion concentration.
• Biological setting: Most biochemical reactions occur in water near 37°C and approximately neutral pH.
• Key distinction: A buffer resists pH change but does not prevent all change; its capacity is limited by the amount of conjugate acid–base pair present.
• Structural basis: Carbohydrates contain multiple hydroxyl groups and usually follow the approximate formula Cn(H2O)n, although many biologically important derivatives do not fit this formula exactly.

II. Acid–Base Chemistry — Proton Transfer in Biological Systems

Acid–base chemistry describes proton donation, proton acceptance, and the equilibria established between conjugate pairs in solution.

A. Acid, Base and Buffers

An acid donates protons, a base accepts protons, and a buffer contains a weak acid and its conjugate base in proportions that resist pH change.

• Brønsted–Lowry acid: A proton donor, such as acetic acid:
  CH₃COOH ⇌ H⁺ + CH₃COO⁻
• Brønsted–Lowry base: A proton acceptor, such as bicarbonate:
  HCO₃⁻ + H⁺ ⇌ H₂CO₃
• Conjugate pair: Removal of H⁺ from an acid produces its conjugate base; CH₃COOH/CH₃COO⁻ is one pair.
• Strength: Strong acids dissociate extensively, whereas weak acids, such as carbonic acid and acetic acid, dissociate incompletely.
• Buffer composition: A useful buffer contains appreciable concentrations of both HA and A⁻, where HA is the weak acid and A⁻ is its conjugate base.

B. Properties of water

Water is a polar, hydrogen-bonding solvent whose ionization and thermal properties make biochemical reactions possible.

• Polarity: Oxygen is more electronegative than hydrogen, giving water partial charges: oxygen is δ− and hydrogen is δ+.
• Hydrogen bonding: Each water molecule can form hydrogen bonds with neighboring molecules, producing cohesion and a relatively high boiling point.
• Solvent action: Ionic and polar substances dissolve because water forms hydration shells around charged particles; Na⁺ is surrounded by the oxygen ends of water.
• Hydrophobic effect: Nonpolar groups cluster together in water, helping drive membrane formation and protein folding.
• Autoionization: Water undergoes reversible ionization:
  H₂O ⇌ H⁺ + OH⁻
  At 25°C, [H⁺][OH⁻] = 1.0 × 10⁻¹⁴, where brackets indicate molar concentration.

C. Concept of pH scale

pH expresses hydrogen-ion concentration logarithmically and provides a convenient measure of acidity.

• Definition:
  pH = −log₁₀[H⁺]
[H⁺] is the hydrogen-ion concentration in mol/L.
• Interpretation: A solution with pH 3 has [H⁺] = 10⁻³ M; it is ten times more acidic than a solution at pH 4.
• Acidic, neutral, alkaline: At 25°C, pH 7 is neutral, values below 7 are acidic, and values above 7 are alkaline.
• Related quantity:
  pOH = −log₁₀[OH⁻] and pH + pOH = 14 at 25°C.
• Biological importance: Blood is maintained near pH 7.4; even small deviations can alter protein charge and enzyme activity.

D. Buffers and its mechanism of action

Buffers act by using a conjugate acid–base pair to consume added hydroxide ions or hydrogen ions.

• Added acid: When H⁺ enters an acetate buffer, acetate consumes it:
  CH₃COO⁻ + H⁺ → CH₃COOH
• Added base: When OH⁻ enters the same buffer, acetic acid neutralizes it:
  CH₃COOH + OH⁻ → CH₃COO⁻ + H₂O
• Mechanistic limit: Buffering is strongest near the pKa of the weak acid and falls when one component becomes nearly depleted.
• Capacity: A concentrated buffer neutralizes more added acid or base than a dilute buffer at the same pH.
• Physiological example: The carbonic acid–bicarbonate system helps stabilize blood pH:
  CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

E. Henderson Hasselbalch equation

The Henderson–Hasselbalch equation relates buffer pH to the pKa and relative concentrations of conjugate base and weak acid.

• Equation:
  
  TEXT

    pH = pKa + log₁₀([A⁻]/[HA])

  
  pH is solution acidity, pKa is acid strength, [A⁻] is conjugate-base concentration, and [HA] is weak-acid concentration.
• Derivation basis: Starting with Ka = [H⁺][A⁻]/[HA], rearrangement and negative logarithms produce the equation.
• Meaning: When [A⁻] = [HA], the logarithm is zero, so pH = pKa.
• Worked example: If pKa = 4.76 and [A⁻]/[HA] = 10, then pH = 4.76 + 1 = 5.76.
• Assumptions: The equation is most useful for weak acids, moderate concentrations, and solutions where activity approximates concentration.

III. Carbohydrate Foundations — Structure and Function

Carbohydrates are polyhydroxy aldehydes, polyhydroxy ketones, or compounds that yield them on hydrolysis. Their many hydroxyl groups make them water-soluble and chemically versatile.

A. Carbohydrates

Carbohydrates function as fuels, energy stores, structural materials, and molecular-recognition components.

• Chemical groups: A typical carbohydrate contains hydroxyl groups and either an aldehyde, as in glucose, or a ketone, as in fructose.
• Energy role: Glucose oxidation yields ATP through glycolysis, the citric acid cycle, and oxidative phosphorylation.
• Storage role: Glycogen stores glucose in animals, while starch stores glucose in plants.
• Structural role: Cellulose strengthens plant cell walls; chitin supports fungal walls and arthropod exoskeletons.
• Recognition role: Carbohydrate chains on glycoproteins and glycolipids contribute to cell adhesion, immune recognition, and blood-group specificity.

B. Classification of carbohydrates

Carbohydrates are classified by the number of sugar units, carbonyl type, and number of carbon atoms.

• Monosaccharides: Single units that cannot be hydrolyzed into smaller carbohydrates; glucose and fructose are examples.
• Oligosaccharides: Short chains containing approximately 2–10 monosaccharide residues; sucrose and lactose are disaccharides.
• Polysaccharides: Long polymers containing many sugar residues; glycogen, starch, and cellulose are examples.
• Aldoses and ketoses: Aldoses contain an aldehyde group, whereas ketoses contain a ketone group; glucose is an aldose and fructose is a ketose.
• Carbon number: Trioses, pentoses, and hexoses contain three, five, and six carbon atoms respectively.

IV. Monosaccharides — Basic Sugar Units

Monosaccharides are the simplest carbohydrates and are the building blocks of oligosaccharides and polysaccharides.

A. Monosaccharides

A monosaccharide is a polyhydroxy aldehyde or ketone that cannot be hydrolyzed into a simpler carbohydrate.

• Glucose: D-glucose is an aldohexose and a major blood fuel; its open-chain form contains an aldehyde at C1.
• Fructose: D-fructose is a ketohexose with a ketone at C2 and occurs in fruits and honey.
• Pentoses: Ribose forms part of RNA, while deoxyribose forms part of DNA.
• Ring formation: Intramolecular reaction between a carbonyl group and hydroxyl group produces a hemiacetal or hemiketal ring.
• Anomeric carbon: The former carbonyl carbon becomes the anomeric carbon; C1 is anomeric in glucose, whereas C2 is anomeric in fructose.

B. Stereo isomerism of monosaccharides

Stereoisomerism results when monosaccharides have the same connectivity but different three-dimensional arrangements.

• Chiral centers: An asymmetric carbon is attached to four different groups; D-glucose has four chiral centers in its open-chain form.
• D and L forms: Configuration is assigned by the chiral carbon farthest from the carbonyl; an OH on the right in a Fischer projection indicates D.
• Enantiomers: D-glucose and L-glucose are non-superimposable mirror images.
• Epimers: Sugars differing at one chiral center are epimers; D-glucose and D-galactose differ at C4.
• Anomers: α- and β-D-glucose differ at the anomeric carbon; in Haworth convention for D-sugars, α has anomeric OH opposite the CH₂OH group, while β is on the same side.
• Mutarotation: α-D-glucose and β-D-glucose interconvert through the open-chain form, changing optical rotation until equilibrium is reached.

C. Sugar derivatives

Sugar derivatives arise when hydroxyl, carbonyl, or other groups of monosaccharides are chemically modified.

• Sugar acids: Oxidation of glucose’s C1 aldehyde produces gluconic acid; oxidation of C6 produces glucuronic acid.
• Sugar alcohols: Reduction of the carbonyl group produces polyols such as sorbitol from glucose.
• Amino sugars: An OH group is replaced by NH₂; glucosamine and N-acetylglucosamine occur in connective tissue and chitin.
• Deoxy sugars: Replacement of OH by H produces deoxyribose, which lacks the 2′-OH found in ribose.
• Phosphate esters: Glucose-6-phosphate traps glucose inside cells and participates in glycolysis.
• Glycosides: The anomeric OH is replaced by an OR or another nucleophile, producing an acetal linkage that cannot readily mutar rotate.

V. Oligosaccharides — Short, Linked Sugar Chains

Oligosaccharides contain a small number of monosaccharides joined by glycosidic bonds formed through condensation.

A. Oligosaccharides

Oligosaccharides are short carbohydrate chains whose linkage position and anomeric configuration determine their properties.

• Glycosidic bond: A bond forms between anomeric carbon of one sugar and an OH group of another, releasing water; maltose contains an α(1→4) bond.
• Disaccharides: Sucrose is glucose + fructose, lactose is galactose + glucose, and maltose is glucose + glucose.
• Reducing sugars: A sugar is reducing when a free anomeric carbon can open to a carbonyl form; lactose and maltose are reducing.
• Nonreducing sugar: Sucrose has both anomeric carbons involved in its α1↔β2 linkage, so it has no free anomeric carbon.
• Biological role: Oligosaccharides attached to proteins and lipids form cell-surface markers and participate in recognition.

VI. Polysaccharides — Storage and Structural Polymers

Polysaccharides are high-molecular-weight carbohydrate polymers whose biological behavior depends on monomer type and linkage pattern.

A. Polysaccharides (storage and structural)

Storage polysaccharides provide glucose reserves, whereas structural polysaccharides provide mechanical strength and resistance to digestion.

• Storage starch: Plant starch contains amylose, mainly unbranched α(1→4)-linked glucose, and amylopectin, which has α(1→6) branches.
• Storage glycogen: Animal glycogen resembles amylopectin but is more highly branched, with branches approximately every 8–12 residues.
• Branching advantage: Many nonreducing ends permit rapid simultaneous glucose release; liver glycogen helps maintain blood glucose.
• Structural cellulose: Cellulose contains β(1→4)-linked glucose; alternating glucose orientation creates straight chains stabilized by hydrogen bonds.
• Structural chitin: Chitin contains β(1→4)-linked N-acetylglucosamine and forms arthropod exoskeletons and fungal cell walls.
• Digestibility contrast: Humans digest α-linkages in starch using amylases but cannot efficiently hydrolyze cellulose’s β(1→4) bonds.

VII. Mucopolysaccharides — Glycosaminoglycan-Rich Polymers

Mucopolysaccharides, more precisely called glycosaminoglycans, are long, negatively charged heteropolysaccharides found mainly in extracellular matrix.

A. Mucopolysaccharides

Mucopolysaccharides consist of repeating disaccharide units containing an amino sugar and usually a uronic acid.

• Repeating unit: Hyaluronic acid contains N-acetylglucosamine and glucuronic acid repeated in β(1→3) and β(1→4) linkages.
• Negative charge: Sulfate and carboxylate groups attract Na⁺ and water, producing hydrated gels in connective tissue.
• Major examples: Chondroitin sulfate occurs in cartilage; dermatan sulfate occurs in skin and blood vessels; heparin has a strong anticoagulant function.
• Mechanical role: Water retention gives cartilage resilience and synovial fluid lubrication; hyaluronic acid also supports tissue spacing.
• Clinical significance: Lysosomal degradation defects cause mucopolysaccharidoses, in which glycosaminoglycans accumulate and damage tissues.
• Protein association: Many glycosaminoglycans attach to core proteins to form proteoglycans, unlike most glycoproteins, which contain shorter and more branched carbohydrate chains.