Rucete ✏ Lehninger Principles of Biochemistry In a Nutshell
3.2 Peptides and Proteins
This chapter introduces how amino acids link to form peptides and proteins, explores their structural features, diversity, and biological significance, and explains the classification and composition of simple and conjugated proteins.
Peptide Bond Formation and Structure
• Peptides are formed by covalent peptide bonds between the α-carboxyl group of one amino acid and the α-amino group of another, with the removal of water (condensation reaction).
• The resulting structure is called a residue; sequences can range from short oligopeptides to long polypeptides and proteins.
• Peptides are named from the N-terminal (amino) end (left) to the C-terminal (carboxyl) end (right); this sequence convention is always followed.
• Peptide bonds are kinetically stable with a half-life of several years under cellular conditions, despite being thermodynamically favored to hydrolyze.
Properties and Ionization of Peptides
• Only the terminal α-amino and α-carboxyl groups in a peptide remain ionizable; all other amino and carboxyl groups are involved in peptide bonds.
• Ionizable side chains (R groups) of certain amino acids contribute to the overall acid-base properties and isoelectric point (pI) of the peptide.
• Like amino acids, peptides and proteins have characteristic titration curves and can be separated or identified by their charge at a given pH.
• The ionization behavior can be affected by the peptide environment, altering pKa values of side chains compared to free amino acids.
Diversity and Biological Roles
• Biologically active peptides vary widely in size—from small di- and tripeptides to polypeptides with thousands of residues.
• Small peptides can serve as hormones (e.g., oxytocin, thyrotropin-releasing factor), toxins (e.g., mushroom poisons), or antibiotics.
• Proteins can consist of one or multiple polypeptide chains (subunits), held together by noncovalent interactions or, in some cases, covalent bonds (e.g., insulin’s disulfide linkages).
• The amino acid composition of proteins is highly variable; certain amino acids may be very abundant or absent depending on the protein's function and structure.
Classification and Composition of Proteins
• The terms "polypeptide" and "protein" are based on size—polypeptides generally have less than 10,000 Da, proteins are larger.
• Multisubunit proteins have more than one polypeptide chain; if two or more subunits are identical, the protein is called oligomeric, and the repeating units are protomers.
• Simple proteins yield only amino acids upon hydrolysis, while conjugated proteins contain additional chemical components (prosthetic groups) such as lipids, carbohydrates, phosphate, metals, or organic molecules.
• Prosthetic groups are critical for the function of conjugated proteins (e.g., heme in hemoglobin, metals in metalloproteins).
In a Nutshell
• Peptides and proteins are polymers of amino acids linked by peptide bonds, ranging from short chains to massive complexes with diverse functions.
• Their structure is defined by amino acid sequence and composition, and their properties are influenced by ionizable groups and prosthetic components.
• Proteins can be simple (amino acids only) or conjugated (with non-amino acid groups), and may consist of single or multiple subunits.
• Understanding peptide and protein structure underpins all of molecular biology, biochemistry, and physiology.