Biochemistry: Macromolecules and Amino Acids

Macromolecules

• Insulin is a protein
• Proteins are one of the four major classes of biological molecules

Amino Acids

• The titration curve of an amino acid shows two pKa values
• The first pKa represents the protonation or deprotonation of the carboxyl group
• Glycine is the only amino acid that is not optically active, because its side chain is only a hydrogen atom
• Cysteine and Methionine are the only two amino acids containing sulfur
• Aside from proline, all other amino acids contain a primary amino group, a carboxyl group, and a hydrogen atom bonded to the alpha carbon
• The chirality of an amino acid derives from the alpha carbon, which is bonded to four different chemical groups
• Glutamate (Glu) has a side chain that can act as an acid or base and participate in acid-base catalysis.

Protein Structure

• Amino acids are joined by peptide bonds through condensation reactions, forming a polypeptide chain
• There are 20 proteinogenic amino acids incorporated into proteins
• Proteins can be modified after translation, including acetylation of lysine
• Protein structure is stabilized by hydrogen bonds, hydrophobic effects, electrostatic interactions, and disulfide bonds.
• The peptide bond can rotate around the Cα – C and the Cα – N bonds, which creates a pivot point at the peptide bond
• Parallel beta-sheets occur when adjacent polypeptide chains are oriented with the N-terminus of one aligned with the C-terminus of the other
• Phosphorylation of a protein is a posttranslational modification that often regulates the function of the protein
• Quaternary structure describes the arrangement of multiple polypeptide chains (subunits) into a functional oligomer
• Primary, secondary, and tertiary protein structures are formed and maintained predominantly by noncovalent bonds
• Protein tertiary structure folds into a specific conformation due to the amino acid sequence and sometimes with the help of chaperones
• Proteins can unfold (denature) due to changes in temperature or pH.

Protein-Ligand Binding

• Myoglobin is a single polypeptide chain that lacks quaternary structure.
• Mutations, like changing an Asp to Met in hemoglobin, can alter the binding affinity for oxygen, changing the binding constants of the protein
• sigmoidal binding curves indicate positive cooperativity. Positive cooperativity means that the binding of one ligand molecule to a protein increases the affinity of the protein for subsequent ligand molecules.
• Heme binds to the protein by noncovalent interactions with the pyrrole groups of the porphyrin ring.
• The porphyrin ring binds ferrous iron (Fe^2+^).
• Heme functions as an oxidation-reduction cofactor during oxygen transport.
• When hemoglobin transitions from the T to the R state, the oxygen ligand is not transferred from one subunit to another. Instead, iron moves into the heme plane, causing a movement of the α-helix containing the proximal His.

Enzyme Structure/Function

• In the induced-fit model, the substrate must bind to the enzyme's active site to induce a conformational change that facilitates the catalytic reaction.
• Enzymes are catalysts that increase the rate of a chemical reaction without being consumed themselves.
• Enzymes are highly specific for their substrates.
• Enzymes lower the activation energy of a reaction.
• The catalytic mechanism of RNase does not involve metal ion catalysis.
• The mechanistic step for chymotrypsin involves covalent catalysis and acid-base catalysis.
• Coenzyme A participates in acyl group transfer reactions
• Zinc ions can stabilize negative charges in the substrate to aid in binding and help stabilize negative charge developed during the transition state.

Inhibitors and Enzyme Kinetics

• Organophosphorus compounds such as sarin are examples of covalent irreversible inhibitors, because they form a stable covalent bond with the enzyme.
• At very high substrate concentrations, the reaction rate approaches the maximum velocity (Vmax) for the enzyme.
• Competitive inhibitors increase the apparent K_M, because the substrate is competing with the inhibitor for binding to the active site.
• Noncompetitive inhibitors decrease the apparent V_max, because they bind to the enzyme at a site other than the active site, altering its activity.
• Allosteric inhibitors bind to the enzyme at a site other than the active site, changing the conformation of the enzyme and reducing its activity.
• β-lactams are a class of antibiotics that inhibit bacterial cell wall synthesis. They do not directly bind to the active site but inhibit the enzyme by blocking the formation of the peptide cross-links in peptidoglycan.

Explore the fascinating world of macromolecules and amino acids in this quiz. Learn about the structure and function of proteins, the importance of different amino acids, and their unique properties. Test your knowledge on titration curves, chirality, and protein structure.