Proteins and Amino Acids

• Amino acids are the building blocks of proteins, each containing a carboxyl group (-COOH), an amino group (-NH2), a hydrogen atom (-H), and a unique side chain (R group).
• Alpha-amino acids are the most important, where the amino and carboxyl groups attach to the same carbon atom (alpha-carbon).
• While there are over 300 amino acids in nature, only 20 are essential for making proteins in the body.
• Amino acids can be classified based on chemical structure, nutritional/biological function, and metabolic fate.

Chemical Structure Classification

• Nonpolar Aliphatic amino acids include Glycine, Alanine, Valine, Leucine, and Isoleucine.
• Aromatic amino acids include Phenylalanine, Tryptophan (essential), and Tyrosine (non-essential).
• Sulfur-containing amino acids are Methionine and Cysteine.
• Hydroxyl-containing amino acids are Serine and Threonine; Methionine and threonine are essential.
• Acidic amino acids are Aspartate and Glutamate, both non-essential.
• Amidic amino acids are Asparagine and Glutamine.
• Basic amino acids are Arginine, Lysine, and Histidine; all are charged and essential.
• Proline is an imino acid that is non-essential.

Nutritional/Biological Classification

• Essential Amino Acids cannot be synthesized and must be obtained from the diet.
• Examples of essential amino acids are Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Lysine, and Leucine.
• Non-Essential Amino Acids can be synthesized by the body.
• Examples of non-essential amino acids are Glycine, Cysteine, Alanine, Tyrosine, Serine, Glutamine, Asparagine, Spartate, and Glutamate.
• Semi-Essential Amino Acids are essential during periods of growth, stress, or illness; Arginine is an example.

Metabolic Fate Classification

• Ketogenic Amino Acids can be converted into ketone bodies; examples include Leucine and Lysine.
• Glucogenic Amino Acids can be converted into glucose.
• Almost all amino acids are glucogenic, except Leucine and Lysine.
• Mixed Amino Acids can be converted into both glucose and ketone bodies; examples include Phenylalanine, Isoleucine, Tyrosine, and Tryptophan.

Uncommon Amino Acids

• Uncommon amino acids are not among the 20 fundamental ones.
• Uncommon amino acids are derived from post-translational modifications or unique synthesis processes and have critical roles in protein function, structure, and biochemical pathways.
• Examples: 4-Hydroxyproline, 5-Hydroxylysine, 6-N-Methyllysine, and γ-Carboxyglutamate.

Selenocysteine

• Selenocysteine is the 21st amino acid.
• It contains selenium instead of sulfur and is derived from serine.
• Selenocysteine is introduced during protein synthesis and not as a post-translational modification.
• It is found in the active sites of oxidation-reduction enzymes like glutathione peroxidase.

Ornithine and Citrulline

• Both are intermediates in the urea cycle.
• The urea cycle plays a key role in nitrogen metabolism

Properties of Amino Acids

• All amino acids are alpha amino acids.
• The amino group is attached to the alpha carbon.
• Glycine lacks an asymmetric alpha carbon.
• Amino acids, except glycine, are asymmetric.
• L-Amino Acids are found in proteins.
• D-Amino Acids are found in some bacterial products.
• Glycine is not optically active.

Amphoteric Nature

• Amino acids have both acidic (COOH) and basic (NH2) groups, allowing them to act as both acids and bases depending on the pH.
• At the Isoelectric Point (pI), an amino acid has no net charge; the COOH is negatively charged, and the NH2 is positively charged.
• A Zwitterion is a molecule with both positive and negative charges.

pH Effects on Amino Acid Behavior:

• At Low pH (Acidic): High hydrogen ion (H+) concentration protonates both amino and carboxyl groups, resulting in an overall positive charge.
• At Neutral pH (Around pI): Amino acid exists as a zwitterion with NH3+ (positively charged) and COO- (negatively charged), resulting in an overall neutral charge.
• At High pH (Basic): Low hydrogen ion (H+) concentration causes both amino and carboxyl groups to lose protons, resulting in an overall negative charge.

Amino Acid Functions Beyond Proteins

• Glycine is for detoxification and synthesizes heme.
• Methionine - methyl donor in metabolism.
• Tyrosine synthesizes thyroid hormones (T3, T4), epinephrine, norepinephrine, and melanin.
• Tryptophan synthesizes niacin (Vitamin B3) and serotonin.
• Histidine synthesizes histamine.
• Aspartate and Glutamine are involved in pyrimidine synthesis.
• Glycine, Aspartic Acid, and Glutamine are involved in purine synthesis.

Introduction to Proteins and Biologically Active Peptides

• Proteins (polypeptides) are amino acid polymers linked by peptide bonds.
• Their structure and function are dictated by the sequence of amino acids.
• Proteins play crucial roles in various biological processes.
• Peptides range in size from two to many thousands of amino acids.
• Biological activities aren't always related to size or molecular weight.
• Even small peptides can have significant biological effects.
• Aspartame (*dipeptide L-aspartyl-L-phenylalanine methyl ester) is a low-calorie artificial sweetener.

Examples of Small Peptides:

• Oxytocin stimulates uterine contractions and plays a crucial role in labor and milk ejection.
• Bradykinin inhibits inflammation and mediates pain.
• Thyrotropin-Releasing Factor stimulates the release of thyroid-stimulating hormone (TSH) from the pituitary.
• Glutathione is an antioxidant that protects cells from oxidative stress.
• Amanitin (toxic peptide) inhibits RNA polymerase in cells, leading to cell death.
• Gramicidin A (antibiotic) disrupts bacterial cell membranes.

Examples of Slightly Larger Peptides and Oligopeptides:

• Insulin regulates glucose metabolism by promoting glucose uptake in cells.
• Glucagon raises blood glucose levels by stimulating glycogen breakdown.
• Corticotropin stimulates the adrenal cortex to release cortisol in response to stress.

Proteins - Definition and Role:

• Proteins are long chains of amino acids with specific sequences, and their structure is directly influenced by the gene sequence.
• A single amino acid change can alter function (e.g., sickle cell anemia).
• Proteins can be classified based on function, shape, and composition.

Protein Classification Based on Shape:

• Globular Protein: spherical, compact, water-soluble, less stable, and biologically active; examples include insulin, myoglobin, antibodies, and enzymes.
• Fibrous Protein: linear, structural, insoluble in water, and more stable; examples include keratin, collagen, elastin(lungs/arteries), and myosin(muscle).

Classification based on Function

• Transport – Hemoglobin, Transferrin
• Catalytic - Enzymes
• Storage - Myoglobin, Ferritin
• Defense – Immunoglobulins

More Protein Functions:

• Structural: provide structure - Collagen, Keratin -Nutrient: provide nutrients - Casein, Albumin -Infective Agents: Prions -Buffering – Albumin, Haptoglobin -Gene expression – Histones, Nucleoproteins -Regulatory – Insulin, Hormone receptors

Protein Classification Based on Composition:

• Simple proteins are composed only of amino acids (e.g., Albumins and Globulins).
• Derived proteins result from simple or complex proteins after hydrolysis or denaturation (e.g., Casein and Peptones).
• Complex Proteins proteins are made from amino acids combined with non-protein parts include glycoproteins and metalloproteins.

Conformation of Proteins:

• Proteins have unique three-dimensional structures, and their function is determined by this structure
• Proteins have four structural levels, including primary, secondary, tertiary, and quaternary.

Primary Structure:

• The sequence of amino acids in a polypeptide chain, held together by peptide bonds.
• It determines the protein's final structure and function, read from left to right.
• Starts with the N-terminal amino acid (free amino group) and ends with the C-terminal amino acid (free carboxyl group).
• Remaining amino acids are called amino acid residues

Secondary Structure:

• Local folding of the polypeptide chain into alpha helices and beta sheets.
• Alpha helix: a right-handed spiral, stabilized by hydrogen bonds.
• Beta sheet: an extended structure with hydrogen bonds between chains.
• The a-helix a spiral structure with peptide bonds coiled tightly inside and peptide bonds coiled tightly inside and side chains sticking out.
• There, are 3.6 amino acids per turn in the a-helix
• B-pleated sheets are stabilized by hydrogen bonds between NH and C=O of adjacent peptide segments.

Tertiary Structure:

• The overall 3D folding of a protein, influenced by covalent bonds (like disulfide bridges) and noncovalent bonds (hydrophobic forces, ionic bonds, and hydrogen bonds).
• Hydrophobic side chains are in the interior, hydrophilic side chains are on the exterior.

Quaternary Structure:

• Refers to is the arrangement of multiple polypeptide chains in a protein, held together by the same forces that stabilize tertiary structure.
• A polypeptide chain is called a subunit, and it has its own primary, secondary, and tertiary structure. -Monomer: 1 subunit -Dimer: 2 subunits -Tetramer: 4 subunits
• Insulin: is made up of two subunits, linked by two disulfide bridges.
• Haemoglobin is a tetramer that’s composed of two identical dimers, (αβ)₁ and (αβ)2.
• Within each Haemoglobin dimer, the two polypeptide chains are tightly held together by hydrophobic interations.
• Homopolymer: is made up of identical subunits.
• Heteropolymer: is made up of different subunits.