Biochemistry: Oxygen Binding and Protein Structure

Biochemistry Lesson & Book Notes

• These notes cover various aspects of biochemistry, including amino acids, peptides, proteins, and protein function.

Lesson 1: Amino Acids

• Amino acids (A.A) are the building blocks of proteins.
• Composed of an amino group, a carboxyl group, a carbon atom, and a side chain (R-group).
• The R-group determines the type of amino acid.
• Amino acids are zwitterionic at neutral pH.
• At low pH, all groups are completely protonated.
• At high pH, all groups donate their protons.
• At a specific pH, called the isoelectric point (pI), the net charge of the amino acid is zero.
• Amino acids are least soluble in water at their pI.

Amino Acid Classification

• Nonpolar, aliphatic: Glycine, Alanine, Proline, Valine, Leucine, Isoleucine, Methionine. These lack charged or polar groups, making them hydrophobic. Proline has a unique cyclic structure.
• Aromatic: Phenylalanine, Tyrosine, Tryptophan. These contain aromatic rings, with tyrosine also having a hydroxyl group.
• Polar, uncharged: Serine, Threonine, Cysteine, Asparagine, Glutamine. These have polar groups like hydroxyl or amide groups, making them more hydrophilic than non-polar amino acids. Cysteine can form disulfide bonds.
• Positively charged: Lysine, Arginine, Histidine. These have positively charged groups (amino groups).
• Negatively charged: Aspartate, Glutamate. These have negatively charged groups (carboxyl groups).

Lesson 2: Peptides & Proteins

• Peptides are short chains of amino acids formed by condensation reactions.
• The primary structure of a protein is the sequence of amino acids.
• The primary structure, or order of amino acids, is crucial because of the significant influence on how a protein folds and its function.
• In a fully extended polypeptide, the phi (φ) and psi (ψ) angles are (almost always) 180°.
• The six atoms around the peptide bond lie in a single plane.

Primary Structure: Possible Secondary Structures

• Possible secondary structures include α-helices and β-sheets.
• Ramachandran plots show the allowed ranges of φ (phi) and ψ (psi) angles for amino acid residues in proteins.
• α-helices are stabilized by hydrogen bonds between the carbonyl oxygen of one amino acid and the amide hydrogen of an amino acid four residues further along the chain. β-sheets are stabilized by hydrogen bonds between polypeptide strands.
• Antiparallel and parallel β-sheets show how the strands are arranged in relation to one another.
• Random coils are also significant, allowing polypeptide flexibility.

Secondary Structures: Loops and Turns

• Loops and turns connect secondary structure elements.
• Loop structures are areas where the polypeptide chain undergoes abrupt turns and changes direction.
• β-turns are loop structures that are often involved in connecting strands in β-sheet structures.
• These are often formed by only 4 amino acid residues.

Tertiary Structure

• Tertiary structure is the overall three-dimensional shape of a polypeptide chain.
• Interactions between R groups of amino acids drive the folding process.
• Various non-covalent interactions (hydrogen bonds, hydrophobic interactions, ionic interactions) determine the overall folding.

Non-Covalent Interactions

• Hydrophobic effect: The tendency of nonpolar molecules to aggregate in water, driving the folding of proteins.
• Hydrogen bonds: Between polar side chains, water molecules, and amino acid backbone atoms.
• Van der Waals interactions: Weak attractive forces between all atoms in close proximity.
• Electrostatic interactions: Between charged side chains (ionic interactions) and between charged groups and polar groups.
• Disulfide bonds: Covalent bonds between cysteine side chains. These are crucial for maintaining the tertiary structure of some proteins.

Quaternary Structure

• The quaternary structure is the arrangement of multiple polypeptide chains in a protein.
• Proteins with multiple subunits have quaternary structure.
• Interactions between the subunits, often via non-covalent interactions, determine the protein's function.

Lesson 3: PTMs & Protein Targeting

• Proteins can be modified and targeted after synthesis by various post-translational modifications (PTMs).
• Signal sequences act as targeting signals that direct proteins to different cellular compartments. A signal recognition particle (SRP) binds the signal peptide, and guides the protein to the appropriate compartment.
• Proteins are sent to their final destination after processing through the endoplasmic reticulum (ER) and the Golgi apparatus.

Lesson 4: Protein Motifs, Domains, and Conserved Regions

• Motifs and domains are recognizable structural patterns in proteins.
• Conserved amino acid residues often play critical roles in protein function.

Lesson 5: Enzymes and Enzyme Kinetics

• Enzymes are biological catalysts that speed up chemical reactions by lowering the activation energy.
• Enzyme kinetics studies the rate of enzymatic reactions.
• Key parameters in enzyme kinetics include Vmax, Km, and kcat.

Lesson 6: In vivo Regulation of Enzymatic Activity

• Enzymes can be regulated by environmental factors.
• Allosteric regulation, covalent modification, and feedback control are mechanisms for changing enzyme activity.

Lesson 7: Protein Function; Structural Proteins & Globular Proteins

• Fibrous proteins include collagen and α-keratin, and play structural roles.
• Globular proteins include hemoglobin and myoglobin, and perform a variety of functions including catalysis, transport, and more.

Practice Questions

• Several practice questions are included on the slides relating to the various topics covered in the course such as general concepts of protein structures and functions, different kinds of protein interactions etc. Individual questions are not listed here.

Feedback Control

• Feedback inhibition is a regulatory mechanism. Product inhibition occurs where an end product of a pathway inhibits an enzyme early in the pathway to prevent overproduction of the product.

Covalent Modification

• Covalent modification is a way to control protein function, by adding or removing groups from amino acids in the proteins.

Proteolytic Cleavage

• Proteolytic cleavage often involves the activation or inactivation of enzymes. Zymogens are inactive precursor forms of enzymes that need this cleavage in order to be active.

Enzymatic Activity and Inhibition

• Irreversible and reversible (competitive, uncompetitive, and non-competitive) inhibition mechanisms.

Protein Interactions with Nucleic Acids (DNA, RNA)

• Protein interactions with nucleic acids involving basic and polar amino acids.

Protein Interactions with Inorganic Molecules

• Enzyme active sites may have inorganic molecules, like specific metal ions.

Discussed topics include:

• Various structures of proteins (e.g., primary, secondary, tertiary, quaternary)
• Interactions between proteins
• Different types of enzyme regulation
• Different examples of proteins (e.g., collagen, α-keratin, hemoglobin, myoglobin)

This quiz explores the concepts of oxygen binding and cooperative binding models in biochemistry. It examines the significance of the sigmoid curve, the role of zinc ions, and the characteristics of protein domains and motifs. Test your knowledge on these fundamental topics in protein science!