Amino Acids and Peptides PDF

Biology Biochemistry I Chapter 3 Amino acids and polypeptides Dr.Enas Sarahna September 2024 Introduction Proteins mediate virtually every process that takes place in a cell, exhibiting an almost endless diversity of functions. Proteins are the most abundant biological mac...

Biology Biochemistry I Chapter 3 Amino acids and polypeptides Dr.Enas Sarahna September 2024 Introduction Proteins mediate virtually every process that takes place in a cell, exhibiting an almost endless diversity of functions. Proteins are the most abundant biological macromolecules, occurring in all cells and all parts of cells. proteins are the most important final products of the information pathways; DNA transcription and RNA translation. Those largely diverse macromolecules are constructed from the same ubiquitous set of 20 amino acids. Cells can produce proteins with strikingly different properties and activities by joining the same 20 amino acids in many different combinations and sequences. Amino acids Proteins are polymers of amino acids, with each amino acid residue joined to its neighbor by a specific type of covalent bond (peptide bond). Proteins were hydrolyzed to their amino acids in order to study the primary sequence. The first discovered amino acid was asparagine and the last was threonine. Every amino acid has a special name commonly derived from the source from which they were isolated for the first time. Amino acids share common structure All 20 of the common amino acids are alpha amino acids. They have a carboxyl group and an amino group bonded to the same carbon atom (the For all the common amino acids except glycine, alpha carbon) the carbon is bonded to four different groups: a carboxyl group, an amino group, an R group, and a hydro gen atom. They differ from each other in their side chains, or R groups, which vary in structure, size, and electric charge. Stereoisomerism in alpha amino acids Because of the tetrahedral arrangement of the bonding orbitals around the alpha carbon atom, the four different groups can occupy two unique spatial arrangements, and thus amino acids have two possible stereoisomers. Enantiomers: are non-superposable mirror images of a molecule. The amino acids in protein are L stereoisomers The amino acid residues in protein molecules are exclusively L stereoisomers. D-Amino acid residues have been found in only a few, generally small peptides, including some peptides of bacterial cell walls and certain peptide antibiotics. The formation of stable, repeating substructures in proteins generally requires that their constituent amino acids be of one stereochemical series. Cells are able to specifically synthesize the L isomers of amino acids because the active sites of enzymes are asymmetric, causing the reactions they catalyze to be stereospecific. Amino acids can be classified by their R groups Amino acids can be classified by their R groups Amino acids can be classified by their R groups Absorbance of UV light by aromatic amino acids Uncommon Amino Acids Also Have Important Functions In addition to the 20 common amino acids, proteins may contain residues created by modification of common residues already incorporated into a polypeptide. 4-hydroxyproline, a derivative of proline, and 5-hydroxylysine, derived from lysine; both are found in collagen, a fibrous protein of connective tissues. 6-N-Methyllysine is a constituent of myosin, a contrac tile protein of muscle. gamma-carboxyglutamate, found in the blood clotting protein prothrombin Uncommon Amino Acids Also Have Important Functions Desmosine, a derivative of four Lys residues, which is found in the fibrous protein elastin. Selenocysteine is a special case. This rare amino acid residue is introduced during protein synthesis rather than created through a postsynthetic modification. It contains selenium rather than the sulfur of cysteine. Ornithine and citrulline deserve special note because they are key intermediates (metabolites) in the biosynthesis of arginine and in the urea cycle. Amino acids can act as acids and bases The amino and carboxyl groups of amino acids, along with the ionizable R groups of some amino acids, function as weak acids and bases. Zwitterion: dipolar ion, can act either as acid or base, has a neutral charge as it has an equal number of positive and negative charges. Substances having this dual (acid-base) nature are amphoteric. Alanine: Amino acids have characteristic titration curves The plot has two distinct stages, corresponding to deprotonation of two different groups on amino acid. Each of the two stages resembles in shape the titration curve of a monoprotic acid, such as acetic acid and can be analyzed in the same way. There is a transitional point between the two stages at pI. The titration curve of alanine Titration Curves Predict the Electric Charge of Amino Acids Another important piece of information derived from the titration curve of an amino acid is the relationship between its net For glycine: charge and the pH of the solution. The characteristic pH at which the net electric charge is zero is called As is evident in Figure 3–10, glycine has a net negative charge at any pH the isoelectric point or isoelectric pH, above its pI and will thus move toward designated pI. the positive electrode (the anode) when placed in an electric field. At any pH below its pI, glycine has a net positive charge and will move toward the negative electrode (the cathode). The ionization of histidine (an amino acid with a titratable side chain). The titration curve of histidine Peptides, and Proteins 21 Formation of a peptide bond by condensation. Amino groups are good nucleophiles, but the hydroxyl group is a poor leaving group and is not readily displaced Polypeptides and proteins Two amino acids can be covalently joined by a peptide bond to yield a dipeptide. few amino acids are joined in this fashion; the structure is called an oligopeptide. many amino acids are joined, the product is called a polypeptide. Polypeptides may have generally Mr below 10,000 and proteins have higher Mr. In a peptide, the amino acid residue at the end with a free α-amino group is the amino– terminal (or N-terminal) residue; the residue at the other end, which has a free carboxyl group, is the carboxyl-terminal (C-terminal) residue. The acid-base behavior of a peptide can be predicted from its free α-amino and α-carboxyl groups as well as the nature and number of its ionizable R groups. Therefore, peptides have characteristic titration curves and a characteristic pI. Amino Acids Proteins are dehydration polymers of amino acids. Each amino acid residue is joined to its neighbor by covalent bond (peptide bond). Residue reflects the loss of the elements of water when one amino acid is joined to another.  Ser–Gly–Tyr–Ala–Leu, or SGYAL. Peptides are named beginning with the amino-terminal residue, which by convention is placed at the left The sequence is read left to right, beginning with the amino-terminal end. 1. Peptides contain only one free -amino group and one free - carboxyl group, at opposite ends of the chain. These groups ionize as they do in free amino acids, although the ionization constants are different because an oppositely charged group is no longer linked to the carbon. 2. All nonterminal amino acids are covalently joined in the peptide bonds, which do not ionize and thus do not contribute to the total acid- base behavior of peptides. 3. The R groups of some amino acids can ionize and in a peptide these contribute to the overall acid-base properties of the molecule. 4. The acid-base behavior of a peptide can be predicted from its free - amino and -carboxyl groups as well as the nature and number of its ionizable R groups. The smallest peptides can have biologically important effects smallest peptides can have biologically important effect like the commercially synthesized dipeptide L-asp–L-phe methyl ester, the artificial sweetener better known as aspartame or NutraSweet. an artificial, non-saccharide sweetener used as a sugar substitute The amino acid composition of proteins is highly variable. The 20 common amino acids almost never occur in equal amounts in a protein. Some amino acids may occur only once or not at all in a given type of protein; others may occur in large numbers The non–amino acid part of a conjugated protein is usually called its prosthetic group Difference between simple protein and complex protein? Small polypeptides and oligopeptides with important biological activity Insulin: 51 amino acids Glucagon: 29 amino acids Vasopressin: 9 amino acids Oxytocin: 9 amino acids Thyroid releasing hormone: 3 amino acids  How to calculate the approximate number of amino acid residues in a simple protein containing no other chemical constituents? Solution: dividing its molecular weight by 110. 1. The average molecular weight of the 20 common amino acids is about 138. 2. If we take into account the proportions in which the various amino acids occur in an average protein the average molecular weight of protein amino acids is nearer to128.(Table 3-1). 3. Because a molecule of water (Mr 18) is removed to create each peptide bond, the average molecular weight of an amino acid residue in a protein is about 128 – 18= 110.  Biologically Active Peptides and Polypeptides Occur in a Vast Range of Sizes Multisubunit proteins: have two or more polypeptide chains associated non-covalently. individual polypeptide chains in a multisubunit protein may be identical or different. Oligomeric: Proteins with at least two identical polypeptide chains (in a multisubunit protein). Protomers: The identical units in the oligomeric proteins. e.g. Hemoglobin: tetramer of four polypeptide subunits dimer of αβ protomers.