Foundations of Biochemistry

Key Elements and Body Composition

The human body is primarily composed of four elements and a variety of organic and inorganic compounds. Understanding their distribution and function is fundamental to biochemistry.

• Four Key Elements: Oxygen (65%), Carbon (18%), Hydrogen (9.5%), Nitrogen (3.2%)—together comprise ~96% of body mass.

• Body Composition: Water (60%), Protein (16%), Triglycerides (13%), Salts (6.2%), Carbohydrates (1.5%), Nucleic acids (0.2%).

• Inorganic Components: Water and salts.

• Organic Components: Carbohydrates, lipids (triglycerides), proteins, nucleic acids.

• Most Abundant Inorganic Compound: Water (H2O), ~60% of body mass.

Body Fluids and Fluid Balance

Body fluids are classified by their location and play a critical role in maintaining homeostasis.

• Intracellular Fluid (ICF): Located inside cells (e.g., cytosol).

• Extracellular Fluid (ECF): Located outside cells (e.g., interstitial fluid, plasma, lymph, cerebrospinal fluid, synovial fluid, digestive fluids).

• Fluid Balance: Maintained when intake equals output; imbalance can lead to dehydration or water intoxication.

Properties of Water

Water is essential for life due to its unique chemical and physical properties.

• Polar Molecule: Enables water to dissolve ionic and polar substances.

• High Heat Capacity and Heat of Vaporisation: Helps regulate body temperature.

• Cohesive and Adhesive: Facilitates transport and lubrication.

• Participates in Chemical Reactions: Hydrolysis and condensation reactions.

Solutions, Electrolytes, and pH

Understanding solutions and electrolytes is crucial for biochemical processes.

• Solution: Homogeneous mixture of solute and solvent.

• Electrolytes: Dissociate into ions and conduct electricity (e.g., NaCl, KCl).

• Non-electrolytes: Dissolve but do not form ions (e.g., glucose).

• Major Electrolytes: ICF: Potassium (K+); ECF: Sodium (Na+), Chloride (Cl-).

• pH: Measure of hydrogen ion concentration; pH 7 is neutral, <7 acidic, >7 alkaline.

• Normal Plasma pH: 7.35–7.45.

Buffer Systems and Acid-Base Disorders

Buffer systems maintain pH within a narrow range, essential for protein and enzyme function.

• Buffer Systems: Bicarbonate, phosphate, and protein buffers.

• Acidosis: Blood pH <7.35; Alkalosis: Blood pH >7.45.

• Major Acid-Base Disorders: Respiratory acidosis, respiratory alkalosis, metabolic acidosis, metabolic alkalosis.

Biomolecules in the Human Body

Types and Properties of Biomolecules

Biomolecules are the building blocks of life, each with distinct structures and functions.

• Proteins: Composed of amino acids; functions include catalysis, defence, structure, movement, regulation, signalling, transport.

• Nucleic Acids: Composed of nucleotides; store and transmit genetic information, regulate cellular activities, energy storage.

• Carbohydrates: Composed of monosaccharides; energy storage and structural support.

• Lipids: Composed of fatty acids; energy storage, membrane formation, cell signalling.

• Common Properties:

  • Contain C, H, O

  • Form polymers via condensation (dehydration synthesis); broken down by hydrolysis

  • Exist as isomers (positional, geometric, optical)

  • Biological properties determined by noncovalent interactions

Noncovalent Interactions

Noncovalent interactions are weak, reversible forces essential for biomolecular structure and function.

• Types: Hydrogen bonds, dipole-dipole, electrostatic, ion-dipole, hydrophobic, van der Waals.

• Roles: Maintain solubility, stabilize higher-order structures, enable biomolecular binding.

Cellular Diversity and Biomolecule Distribution

Cell types differ due to variations in biomolecule composition and structure.

• Plasma Membrane: Lipids (phospholipids, cholesterol), proteins, carbohydrates.

• Cytosol: Primarily proteins, water, electrolytes.

• Organelles: Proteins, lipids, nucleic acids, carbohydrates.

• Cytoskeleton: Proteins.

Amino Acids and Protein Structure

Basic Structure and Stereochemistry of Amino Acids

Amino acids are the monomers of proteins, each with a unique side chain (R group).

• Structure: Central α-carbon, amino group (-NH2), carboxyl group (-COOH), hydrogen atom, variable R group.

• Stereochemistry: Most amino acids are chiral, existing as L- and D- isomers; L-amino acids are used in proteins.

Classification of Amino Acid R Groups

The chemical properties of amino acids are determined by their R-side chains.

• Non-polar aliphatic

• Aromatic

• Sulfur-containing

• Alcohol-containing

• Amide-containing

• Acidic (negatively charged)

• Basic (positively charged)

• Imino (proline)

Essential vs Non-Essential Amino Acids

Essential amino acids must be obtained from the diet; non-essential amino acids are synthesized by the body.

• Example: Phenylalanine (essential) is converted to tyrosine (non-essential) by phenylalanine hydroxylase.

Phenylketonuria (PKU)

PKU is a metabolic disorder caused by defective phenylalanine hydroxylase, leading to toxic accumulation of phenylalanine.

• Symptoms: Intellectual disability, neurological damage.

• Treatment: Early diagnosis and dietary restriction of phenylalanine.

Zwitterions and Buffering Capacity

Amino acids can exist as zwitterions, making them effective buffers.

• Zwitterion: Contains both positive (NH3+) and negative (COO-) charges, overall neutral.

• Charge at Different pH:

  • pH = pI: Neutral (zwitterion)

  • pH < pI: Positive

  • pH > pI: Negative

• Buffering: Amino acids accept/donate H+ to resist pH changes.

Peptide Bond Formation and Protein Structure

Amino acids join via peptide bonds to form proteins, which have hierarchical structures.

• Peptide Bond: Formed by condensation (dehydration) reaction between carboxyl and amino groups.

• Primary Structure: Linear sequence of amino acids.

• Secondary Structure: Local folding (α-helices, β-sheets) stabilized by hydrogen bonds.

• Tertiary Structure: Overall 3D shape stabilized by R group interactions.

• Quaternary Structure: Association of multiple polypeptide chains.

Oligopeptides and Protein Denaturation

Oligopeptides are short chains of amino acids; denaturation disrupts protein structure and function.

• Oligopeptides: Short, cannot fold into higher-order structures; often function in cell communication (e.g., peptide hormones).

• Denaturation: Loss of secondary, tertiary, quaternary structure; primary structure remains intact; caused by heat, pH, chemicals.

Protein Hydrolysis

Hydrolysis breaks peptide bonds, yielding individual amino acids.

• Reaction: Addition of water across peptide bond.

• Result: Protein broken into amino acids or smaller peptides.

Effects of Temperature and pH on Proteins

Proteins are sensitive to changes in temperature and pH, which can disrupt their structure and function.

• Normal Conditions: 37°C, pH 7.35–7.45.

• Disruption: Breaks non-covalent interactions, causes denaturation, impairs function.

Major Functions of Proteins

• Catalysis (enzymes)

• Defence (antibodies)

• Structure and motion (e.g., keratin, myosin)

• Regulation (e.g., p53)

• Transport (e.g., haemoglobin)

• Signalling (e.g., insulin)

Enzymes

Functions and Properties of Enzymes

Enzymes are biological catalysts that accelerate chemical reactions without being consumed.

• Lower activation energy

• Increase reaction rate

• Highly specific for substrates

• Reusable

• Regulate metabolic pathways

Cofactors and Coenzymes

Some enzymes require non-protein helpers for activity.

• Cofactors: Non-protein helpers; can be inorganic ions (Ca2+, Zn2+, Mg2+, Fe2+/3+) or organic molecules (coenzymes).

• Coenzymes: Organic cofactors, often vitamin-derived (e.g., NAD+, FAD, Coenzyme A).

• Prosthetic Groups: Permanently attached cofactors (e.g., FAD in flavoproteins).

• Coenzymes: Temporarily attached, participate in reaction, then detach (e.g., NAD+).

Enzyme Classification and Naming

Enzymes are classified by the type of reaction they catalyse.

Most enzyme names end with -ase (e.g., lactase, lipase, protease, amylase, DNA polymerase), but some have historical names (e.g., pepsin, trypsin, thrombin).

Enzyme-Substrate Interaction Models

Two models explain how enzymes bind substrates:

• Lock-and-Key Model: Rigid active site, substrate fits exactly; explains specificity.

• Induced-Fit Model: Flexible active site, changes shape upon substrate binding; explains catalytic efficiency.

Allosteric Regulation

Allosteric enzymes have regulatory sites that modulate activity.

• Negative Allosteric Control: Inhibitor binds allosteric site, decreases activity.

• Positive Allosteric Control: Activator binds allosteric site, increases activity.

Enzyme Inhibition

Enzyme activity can be inhibited in several ways:

• Irreversible Inhibition: Inhibitor binds permanently, enzyme inactivated (e.g., aspirin, organophosphates).

• Competitive Reversible Inhibition: Inhibitor competes for active site; increasing substrate concentration can overcome inhibition.

• Non-Competitive Reversible Inhibition: Inhibitor binds allosteric site, alters enzyme shape; cannot be overcome by increasing substrate.

Zymogens (Proenzymes)

Zymogens are inactive enzyme precursors, activated by proteolytic cleavage.

• Example: Pepsinogen (inactive) is converted to pepsin (active) by HCl in the stomach.

• Other examples: Trypsinogen → Trypsin, Chymotrypsinogen → Chymotrypsin.

Effects of Temperature and pH on Enzyme Activity

Enzyme activity depends on optimal temperature and pH.

• Temperature: Activity increases with temperature up to optimum (~37°C for humans); denaturation occurs above optimum.

• pH: Each enzyme has an optimum pH; extreme pH disrupts structure and activity.

• Examples: Pepsin (pH ~2, stomach), Trypsin (pH ~8, small intestine).

Key Equations

pH Calculation

• pH Equation:

Isoelectric Point (pI) of Amino Acids

• pI Equation (for amino acids with two ionizable groups):

Michaelis-Menten Equation (Enzyme Kinetics)

• Michaelis-Menten Equation:

Summary Table: Enzyme Classes

Additional info:

• Expanded explanations of noncovalent interactions, protein structure hierarchy, and enzyme regulation mechanisms were added for academic completeness.

• Key equations and summary tables were included to aid exam preparation.