Study Notes on Proteins

Proteins are derived from the Greek word "proteios", meaning "first of rank".
They are the most abundant biomolecule in the cell.
Polypeptides: A single linear chain of amino acids.
Proteins: Composed of one or more polypeptide chains folded into specific conformations.
Molecular Weight (MW) of proteins is generally ≥ 10,000 Da (Dalton).

Expressed in Daltons (Da or D), a unit of mass about equal to that of a hydrogen atom.

Simple Proteins: Yield only amino acids upon hydrolysis.
Conjugated Proteins: Composed of simple proteins plus non-protein substances.
- Examples of Conjugated Proteins include:
- Nucleoproteins: Complex of nucleic acid and protein.
- Glycoproteins: Complex of carbohydrate and protein.
- Lipoproteins: Complex of lipid and protein.
- Phosphoproteins: Complex of phosphate groups and protein.
- Hemoproteins: Contain heme groups and protein.
- Flavoproteins: Contain flavin nucleotides and protein.
- Metalloproteins: Contain metal ions and protein.

Biological Catalysts: Such as enzymes that catalyze biological reactions.
Transport Proteins: Carry specific molecules or ions from one organ to another.
Nutrient and Storage Proteins: Mobilized by the body for building blocks or energy.
Defense Proteins: Protect organisms against invasions by foreign substances.
Contractile Proteins: Allow for contraction, shape change, or movement of cells and organisms.
Structural Proteins: Provide support and protection for biological structures.
Regulatory Proteins: Regulate physical or cellular activities.

Globular Proteins:
- Polypeptide chains coiled into a compact spherical shape.
- Soluble in water, allowing mobility within cells.
- Examples: amylase, hemoglobin.
Fibrous Proteins:
- Polypeptide chains arranged side-by-side in long filaments.
- Insoluble in water and provide mechanical strength.
- Examples: collagen.

Albumins: Soluble in water and dilute aqueous solutions (e.g., egg albumin, lactalbumin).
Globulins: Soluble in dilute salt solutions, but insoluble or sparingly soluble in water (e.g., ovoglobulin, myosin).
Glutellins: Soluble in dilute solutions of acids and bases (e.g., glutellin from wheat).
Albuminoids: Insoluble in most ordinary solvents (e.g., keratins from hair).
Prolamins: Soluble in 70-80% alcohol (e.g., zein from corn).

Primary Structure:
- Defined as the linear sequence of amino acids from the N-terminus to the C-terminus.
- Determines the structural and functional properties of the protein.
Secondary Structure:
- Consists of the spatial arrangement of amino acid residues near each other in sequence.
- Characterized by regular folding patterns such as alpha (α)-helix and beta (β)-pleated sheets.
Tertiary Structure:
- Overall three-dimensional arrangement of all atoms within a protein.
- Results from specific folding into unique shapes that create binding sites.
Quaternary Structure:
- Organization of multiple polypeptide chains (subunits) in a multi-subunit protein.
- Subunits are held together by non-covalent interactions.
- Example: Hemoglobin as an oligomeric protein composed of four polypeptide chains.

The amino acid sequence forms the protein's primary structure, dictating its overall architecture and functional capabilities.
Example: Sickle Cell Hemoglobin, where Glu6 is replaced by Val, affecting structure and function.

Overall 3D arrangement of all atoms, crucial for the function of the protein.
Stabilized by multiple interactions:
1. Hydrophobic Interactions: Non-polar residues cluster at the protein interior.
2. Hydrogen Bonds: Between side groups or peptide bonds.
3. Electrostatic Interactions: Charged side chains interact (e.g., carboxylate groups of aspartate/glutamate, and ammonium groups of lysine).
4. Disulfide Bonds/Bridges: Covalent bonds formed between cysteine residues (—S—S—).

Describes the combination and arrangement of multiple polypeptide subunits.
Subunits can be either homo-multimers (identical subunits) or hetero-multimers (different subunits).
Example: Hemoglobin consists of four polypeptide chains and heme groups forming a stable multimeric structure.

Protein folding gives the molecule its three-dimensional shape, essential for functionality, such as forming binding sites.
Folding is influenced significantly by the protein's amino acid sequence and is typically driven by minimizing free energy, leading to a stable conformation.
In an aqueous environment, non-polar (hydrophobic) side chains are oriented towards the interior while polar (hydrophilic) side chains remain on the surface.
Molecular chaperones may assist in protein folding stability.

Misfolded proteins need to be targeted for degradation to prevent disease.
Accumulation of misfolded proteins can lead to conditions such as:
- Alzheimer’s Disease
- Parkinson’s Disease
- Mad Cow Disease
- Senile Dementia

Alteration of secondary, tertiary, and quaternary structures while preserving the primary structure of proteins; peptide bonds resist disruption.
Can lead to a loss or significant reduction of biological activity.

Physical agents: heat, extreme pH levels.
Chemical agents include:
- Strong acids and bases.
- Heavy metal cations (e.g., Pb²⁺, Hg²⁺).
- Alkaloidal reagents (e.g., trichloroacetic acid).
- Organic solvents (e.g., ethanol, acetone).