Foundations of Biochemistry: Body Fluids, Biomolecules, Proteins, Enzymes, and Nucleic Acids

Foundations of Biochemistry

Key Elements and Body Composition

The human body is primarily composed of a few key elements and a mixture of organic and inorganic compounds. Understanding these components is fundamental to biochemistry.

• Four Key Elements: Oxygen (65%), Carbon (18%), Hydrogen (9.5%), Nitrogen (3.2%) – together, they make up ~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, proteins, nucleic acids.

Body Fluids and Electrolytes

Body fluids are distributed in different compartments and are essential for physiological processes.

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

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

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

• Fluid Balance: Maintained when intake equals output; imbalances can cause dehydration or water intoxication.

Properties of Water

Water is the most abundant inorganic compound in the body and is vital for life due to its unique properties.

• Polarity: Water is a polar molecule, making it an excellent solvent (the "universal solvent").

• High Heat Capacity and Vaporization: Helps regulate body temperature.

• Cohesion and Adhesion: Important for transport and lubrication.

• Participation in Chemical Reactions: Acts as a reactant or product in many biochemical reactions.

pH and Buffer Systems

Maintaining pH is crucial for cellular function. The body uses buffer systems to resist changes in pH.

• pH: A measure of hydrogen ion concentration; $\mathrm{pH} = -\log_{10}[\mathrm{H}^+]$

• Normal Plasma pH: 7.35–7.45.

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

• Acid-Base Disorders: Respiratory/metabolic acidosis and alkalosis.

Biomolecules

Types and Properties

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

Biomolecule	Basic Structure	Major Functions
Proteins	Amino acids	Catalysis, defence, structure, movement, regulation, signalling, transport
Nucleic acids	Nucleotides	Genetic information storage and transmission, energy storage
Carbohydrates	Monosaccharides	Energy storage, structural support
Lipids	Fatty acids	Energy storage, membrane formation, signalling

• Common Properties:

  1. Contain C, H, O (and sometimes N, P, S).

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

  3. Exist as isomers (positional, geometric, optical).

  4. Biological properties determined by noncovalent interactions (hydrogen bonds, van der Waals, etc.).

Amino Acids and Proteins

Amino Acid Structure and Stereochemistry

Amino acids are the monomers of proteins, each with a central α-carbon, amino group, carboxyl group, hydrogen atom, and variable R group.

• Stereochemistry: Most amino acids are chiral (except glycine); L-amino acids are used in proteins.

• R-Side Chain Groups: Non-polar aliphatic, aromatic, sulfur-containing, alcohol-containing, amide-containing, acidic, basic, imino (proline).

Essential vs. Non-Essential Amino Acids

• Essential: Must be obtained from the diet.

• Non-Essential: Synthesized by the body from metabolic intermediates (e.g., phenylalanine → tyrosine via phenylalanine hydroxylase).

Phenylketonuria (PKU)

PKU is a genetic disorder caused by mutations in phenylalanine hydroxylase, leading to toxic accumulation of phenylalanine and neurological damage if untreated.

Zwitterions and Buffering

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

• Buffering: Amino acids can accept or donate H+, making them effective buffers.

Condition	Overall Charge
pH = pI	Neutral (zwitterion)
pH < pI	Positive
pH > pI	Negative

Peptide Bond Formation and Protein Structure

• Peptide Bond: Formed by condensation between the carboxyl group of one amino acid and the amino group of another, releasing water.

• Protein Structure:

  1. Primary: Linear amino acid sequence.

  2. Secondary: Local folding (α-helix, β-sheet) stabilized by hydrogen bonds.

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

  4. Quaternary: Association of multiple polypeptide chains.

Protein Denaturation and Hydrolysis

• Denaturation: Loss of 3D structure (secondary, tertiary, quaternary) due to heat, pH, chemicals; primary structure remains intact.

• Hydrolysis: Addition of water breaks peptide bonds, yielding amino acids.

Protein Function and Examples

• Functions: Catalysis, defence, structure/motion, regulation, transport, signalling.

• Structure-Function Relationship: Protein function depends on precise 3D structure; mutations can cause diseases (e.g., sickle-cell anemia, PKU, cystic fibrosis).

Enzymes

Enzyme Function and Cofactors

Enzymes are biological catalysts that accelerate reactions by lowering activation energy without being consumed.

• Cofactors: Non-protein helpers (inorganic ions or organic coenzymes) required for enzyme activity.

Term	Definition
Cofactor	Non-protein helper for enzyme activity
Coenzyme	Organic cofactor, binds temporarily
Prosthetic group	Permanently attached cofactor
Inorganic cofactor	Metal ion (e.g., Ca2+, Zn2+)

Enzyme Classification

Class	Reaction Catalysed	Example
Oxidoreductases	Oxidation-reduction	Lactate dehydrogenase
Transferases	Transfer of functional groups	Hexokinase
Hydrolases	Hydrolysis	Lipase, Trypsin
Lyases	Bond formation/breaking (not hydrolysis/oxidation)	Pyruvate decarboxylase
Isomerases	Isomerization	Phosphoglucose isomerase
Ligases	Joining molecules (ATP required)	DNA ligase

Enzyme-Substrate Interaction Models

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

• Induced-Fit Model: Flexible active site, changes shape to fit substrate, better explains catalytic efficiency.

Allosteric Regulation

• Allosteric Enzyme: Has both active and allosteric sites; regulatory molecules bind allosteric site to modulate activity.

• Negative Allosteric Control: Inhibitor binding decreases activity.

• Positive Allosteric Control: Activator binding increases activity.

Enzyme Inhibition

• Irreversible Inhibition: Inhibitor binds permanently, inactivating enzyme (e.g., aspirin on COX).

• Competitive Reversible Inhibition: Inhibitor resembles substrate, binds active site; can be overcome by increasing substrate.

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

Zymogens

• Zymogen: Inactive enzyme precursor, activated by proteolytic cleavage (e.g., pepsinogen → pepsin).

Effects of pH and Temperature

• Temperature: Activity increases with temperature up to optimum (~37°C), then declines due to denaturation.

• pH: Each enzyme has an optimum pH; deviations disrupt structure and function (e.g., pepsin pH ~2, trypsin pH ~8).

Nucleic Acids

Nucleotides and Nucleic Acids

• Nucleotide: Monomer with pentose sugar, nitrogenous base, phosphate group.

• Nucleic Acid: Polymer of nucleotides (DNA or RNA).

DNA and RNA Structure and Function

• DNA: Double-stranded helix, deoxyribose sugar, bases A, T, C, G; stores genetic information.

• RNA: Single-stranded, ribose sugar, bases A, U, C, G; involved in protein synthesis.

Central Dogma of Molecular Biology

• Flow of Information: DNA → mRNA → Protein

• Transcription: DNA is transcribed to mRNA.

• Translation: mRNA is translated to protein.

ATP: The Energy Currency

• Structure: Adenine, ribose, three phosphates.

• Function: Stores and releases energy for cellular processes via hydrolysis of phosphate bonds.

DNA Packaging and Structure

• Chromosomes: DNA is wrapped around histones to fit in the nucleus.

• DNA Structure: Two antiparallel strands held by complementary base pairing (A-T, C-G) and phosphodiester bonds.

• Directionality: 5' end (phosphate) to 3' end (hydroxyl).

Transcription and Translation

• Transcription: RNA polymerase synthesizes RNA from DNA template; mRNA is complementary to template strand.

• Translation: Ribosomes read mRNA codons, tRNA brings amino acids, peptide bonds form to create proteins.

• Codon: Three-nucleotide sequence on mRNA specifying an amino acid.

• Anticodon: Three-nucleotide sequence on tRNA complementary to mRNA codon.

• Start Codon: AUG (methionine); Stop Codons: UAA, UAG, UGA.

• Genetic Code: Universal (same in most organisms), degenerate (multiple codons per amino acid).

Genetic Mutations and Diseases

Types of Mutations

• Silent: No change in amino acid sequence.

• Missense: Single amino acid change.

• Nonsense: Premature stop codon, truncated protein.

• Frameshift: Insertion/deletion alters reading frame, usually nonfunctional protein.

Genetic Diseases

• Early-onset Familial Alzheimer's Disease: Missense mutations in APP or related genes increase amyloid-β, causing neurodegeneration.

• Cystic Fibrosis: Nonsense mutations in CFTR gene produce defective chloride channels, leading to thick mucus and organ dysfunction.

• Tay-Sachs Disease: Frameshift mutation in HEXA gene leads to nonfunctional HexA enzyme, accumulation of GM2 ganglioside, and neurodegeneration.

Summary Table: Mutation Types and Effects

Mutation Type	Effect on Protein
Silent	No change in amino acid sequence
Missense	Single amino acid substitution
Nonsense	Premature stop, truncated protein
Frameshift	Altered reading frame, abnormal protein

Key Equations

• pH Calculation: $\mathrm{pH} = -\log_{10}[\mathrm{H}^+]$

• Peptide Bond Formation (Condensation): $\text{Amino acid}_1 + \text{Amino acid}_2 \rightarrow \text{Dipeptide} + \mathrm{H}_2\mathrm{O}$

• ATP Hydrolysis: $\mathrm{ATP} + \mathrm{H}_2\mathrm{O} \rightarrow \mathrm{ADP} + \mathrm{P_i} + \text{energy}$

Additional info:

• Some explanations and examples have been expanded for clarity and completeness.

• Tables have been reconstructed to summarize key comparisons and classifications.