BackChapter 19: Proteins – Structure, Function, and Clinical Aspects
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Introduction
Overview of Proteins
Proteins are the most abundant and functionally diverse biomolecules in living systems. The term proteios means 'of first importance', reflecting their essential role in virtually every biological process. All proteins are linear polymers of amino acids, and a typical human cell contains approximately 9,000 different proteins, while the entire human body has about 100,000 distinct proteins.
Key Point: Proteins are vital for life and exhibit a wide range of functions.
Example: Enzymes, structural proteins, hormones, and antibodies.
Functions of Proteins
Diversity of Protein Functions
Proteins perform numerous roles in biological systems, including structural, catalytic, transport, and regulatory functions.
Structure: Collagen and keratin provide structural support to skin, bone, hair, and nails.
Catalysts: Enzymes catalyze nearly all biochemical reactions.
Movement: Myosin and actin are responsible for muscle contraction.
Transport: Hemoglobin transports oxygen and carbon dioxide; other proteins facilitate molecular transport across membranes.
Hormones: Insulin, oxytocin, and growth hormone regulate physiological processes.
Protection: Antibodies defend against pathogens; fibrinogen is involved in blood clotting.
Storage: Casein (milk), ovalbumin (eggs), and ferritin (liver) store nutrients and iron.
Regulation: Certain proteins control gene expression.
Fibrous vs. Globular Proteins
Classification Based on Structure and Solubility
Proteins are classified as either fibrous or globular based on their structure and solubility.
Fibrous Proteins: Insoluble in water; serve structural roles (e.g., collagen).
Globular Proteins: More soluble in water; perform non-structural functions (e.g., hemoglobin).
Amino Acids
Structural Units of Proteins
All proteins are composed of amino acids, which contain both an amino group and a carboxyl group. Although over 300 amino acids exist in nature, only 20 are commonly found in human proteins.
α-Amino Acid: The amino group is attached to the carbon atom adjacent to the carboxyl group.
Chirality of Amino Acids
Optical Isomerism
Except for glycine, all protein-derived amino acids are chiral due to the presence of a stereocenter at the α-carbon. Amino acids exist as optical isomers, with the L-configuration being predominant in proteins.
Example: D-Alanine vs. L-Alanine (Fischer projections).
Comparison: Monosaccharides have D-configuration; amino acids have L-configuration.
Amino Acids: Classification
Classification Based on Side Chain Polarity
The chemical nature of the side chain (R group) determines the classification of amino acids into four groups:
Non-polar side chains (hydrophobic): Glycine, Alanine, Valine, Leucine, Isoleucine, Phenylalanine, Tryptophan, Methionine, Proline
Polar side chains (hydrophilic): Serine, Threonine, Tyrosine, Asparagine, Glutamine, Cysteine
Acidic side chains (hydrophilic): Aspartic acid, Glutamic acid
Basic side chains (hydrophilic): Histidine, Lysine, Arginine
1) AA with Non-Polar Side Chains
These amino acids have hydrophobic side chains and are typically found in the interior of proteins.
2) AA with Polar Side Chains
These amino acids have hydrophilic side chains and are often located on the protein surface.
3) AA with Acidic Side Chains
Aspartic acid and glutamic acid have carboxyl groups that are negatively charged at physiological pH.
4) AA with Basic Side Chains
Histidine, lysine, and arginine have nitrogen atoms that are positively charged at physiological pH.
Amino Acids: Abbreviations and Symbols
Standardized Nomenclature
Amino acids are represented by one- and three-letter abbreviations based on their names and properties.
Unique First Letter | Most Commonly Occurring | Similar Sounding Names | Letter Close to Initial |
|---|---|---|---|
Cys (C), His (H), Ile (I), Met (M), Ser (S), Val (V) | Ala (A), Gly (G), Leu (L), Pro (P), Thr (T) | Arg (R), Asn (N), Asp (D), Glu (E), Gln (Q), Phe (F), Tyr (Y), Trp (W) | Asx (B), Glx (Z), Lys (K), X (undetermined) |
Protein-Derived Amino Acids
Structural Features
All 20 are α-amino acids.
For 19, the α-amino group is primary; for proline, it is secondary (imino acid).
Except glycine, all have a stereocenter at the α-carbon.
Isoleucine and threonine have a second stereocenter.
Location of Amino Acids in Proteins
Hydrophobic vs. Hydrophilic Distribution
Proteins fold so that hydrophobic amino acids are buried in the interior, while hydrophilic amino acids are exposed on the surface, interacting with water.
Amino Acids: Important Aspects
Biochemical Roles and Clinical Relevance
Tryptophan: Precursor for serotonin and niacin.
Phenylalanine, Tyrosine: Precursors for catecholamines.
Valine, Leucine, Isoleucine: Branched-chain amino acids; abnormal metabolism causes maple syrup urine disease.
Proline: Disrupts normal secondary structure due to its cyclic nature.
Methionine: Sulfur-containing; part of S-adenosylmethionine (SAM), a methyl donor.
Serine, Threonine: Sites for O-linked glycosylation (Golgi apparatus).
Asparagine: Site for N-linked glycosylation (endoplasmic reticulum).
Cysteine: Forms disulfide bonds, stabilizing tertiary structure.
Cysteine
Disulfide Bond Formation
The sulfhydryl (-SH) group of cysteine can be oxidized to form a disulfide (-S-S-) bond, which stabilizes protein structure.
Equation: (oxidation)
What are Zwitterions?
Ionization of Amino Acids
Amino acids in aqueous solution exist as zwitterions, containing both a positively charged ammonium group and a negatively charged carboxylate group.
Un-ionized form:
Zwitterion form:
Ionization and pH
Effect of pH on Amino Acid Charge
The net charge of an amino acid depends on the pH of the solution:
Acidic pH: Amino acid carries a net positive charge.
Neutral pH: Amino acid is a zwitterion (net charge zero).
Basic pH: Amino acid carries a net negative charge.
Equation (acid addition):
Equation (base addition):
Isoelectric Point of Amino Acid
Definition and Table
The isoelectric point (pI) is the pH at which the majority of molecules have no net charge.
Nonpolar & Polar Side Chains | pI | Acidic Side Chains | pI | Basic Side Chains | pI |
|---|---|---|---|---|---|
Alanine | 6.01 | Aspartic acid | 2.77 | Arginine | 10.76 |
Asparagine | 5.41 | Glutamic acid | 3.22 | Histidine | 7.59 |
Cysteine | 5.07 | Lysine | 9.74 | ||
Glutamine | 5.65 | ||||
Glycine | 5.97 | ||||
Isoleucine | 6.02 | ||||
Leucine | 6.01 | ||||
Methionine | 5.74 | ||||
Phenylalanine | 5.48 | ||||
Serine | 5.68 | ||||
Threonine | 5.60 | ||||
Tyrosine | 5.66 | ||||
Tryptophan | 5.89 | ||||
Valine | 5.97 |
Proteins: Isoelectric Point
Behavior of Proteins as Zwitterions
Proteins also have an isoelectric point (pI). At pI, the protein has no net charge; above pI, it is negatively charged; below pI, it is positively charged. Proteins are least soluble at their isoelectric point and can be precipitated from solution at this pH.
Example: Hemoglobin pI = 6.8; Serum albumin pI = 4.9
Uncommon Amino Acids
Post-Translational Modifications
Some proteins contain amino acids other than the standard 20, produced by post-translational modifications (e.g., hydroxyproline, hydroxylysine).
Peptides and Proteins
Definitions
Peptide: Short polymer of amino acids joined by peptide bonds.
Dipeptide: Two amino acids joined by a peptide bond.
Tripeptide: Three amino acids joined by peptide bonds.
Polypeptide: Many amino acids joined by peptide bonds.
Protein: Macromolecule containing at least 30–50 amino acids joined by peptide bonds.
Levels of Organization in Protein Structure
Hierarchy of Protein Structure
Primary Structure: Sequence of amino acids in a polypeptide chain (N-terminal to C-terminal).
Secondary Structure: Localized conformations (α-helix, β-pleated sheet, random coil).
Tertiary Structure: Complete three-dimensional arrangement of amino acids in a polypeptide chain.
Quaternary Structure: Spatial relationship and interactions between subunits in a protein with more than one polypeptide chain.
Table: Levels of Organization in Protein Structure
Level of Structure | Basis of Structure | Kinds of Bonds and Interactions Involved |
|---|---|---|
Primary | Amino acid sequence | Covalent peptide bonds |
Secondary | Folding into α-helix, β-sheet, or random coil | Hydrogen bonds |
Tertiary | Three-dimensional folding of a single polypeptide chain | Disulfide bonds, hydrogen bonds, ionic bonds, van der Waals interactions, hydrophobic interactions |
Quaternary | Association of two or more folded polypeptides to form a multimeric protein | Same as for tertiary structure |
Additional info: These notes cover the essential biochemistry of proteins, including their structure, function, and clinical relevance, suitable for college-level study and exam preparation.
