Biomolecule Amino Acids, Peptides, and Proteins Lecture 5 Dr. Aparna Islam 1

2 Amino acids are the fundamental building blocks of proteins Amino acids contain a basic amino group and an acidic carboxyl group Amino Acids

3 Structures of Amino Acids In neutral solution, the COOH is ionized and the NH 2 is protonated The resulting structures have “+” and “-” charges (a dipolar ion, or zwitterion) They are like ionic salts in solution

Proteins – Peptides from Amino Acids Amino acids are joined as amides/ peptides between the  NH 2 of one amino acid and the  CO 2 H to the next amino acid through peptide/ amid bond Chains with fewer than 50 units are called peptides (some have biological function) Protein: large chains that have structural or catalytic functions in biology 4

5 20 amino acids form proteins All are  -amino acids - the amino and carboxyl are connected to the same C They differ by the other substituent attached to the  carbon, called the R group, with H as the fourth substituent constant Proline is a five-membered secondary amine, with N and the  C part of a five-membered ring The Common Amino Acids

6 Determined by the “R group” Amino acids may be: Non-polar Uncharged, polar Positively charged, polar Negatively charged, polar Properties of Amino Acids

Leucine L, Leu Lysine K, Lys Methionine M, Met Phenylalanine F, Phe Proline P, Pro Serine S, Ser Threonine T, Thr Tryptophan W, Trp Tyrosine Y, Tyr Valine V, Val 7 Alanine A, Ala Arginine R, Arg Asparagine N, Asn Aspartic acid D, Asp Cysteine C, Cys Glutamine Q, Gln Glutamic Acid E, Glu Glycine G, Gly Histidine H, His Isoleucine I, Ile 20 Amino acids Abbreviations and Codes

8 Types of R residues in the side chains Neutral: Fifteen of the twenty have neutral side chains Asp and Glu have a second COOH and are acidic Lys, Arg, His have additional basic amino groups side chains (the N in tryptophan is a very weak base) Cys, Ser, Tyr (OH and SH) are weak acids that are good nucleophiles

9 Essential Amino Acids All 20 of the amino acids are necessary for protein synthesis Humans can synthesize only 10 of the 20 The other 10 must be obtained from food

10 Peptides and Proteins Proteins and peptides are amino acid polymers in which the individual amino acid units, called residues, are linked together by peptide bonds or amide bonds An amino group from one residue forms an peptide/ amide bond with the carboxyl of a second residue

11 Peptide bond Protein is a chain of amino acids linked by peptide bonds Peptide bonds are o Type of covalent bond o Links amino group of one amino acid with carboxyl group of next o Forms through condensation reaction

12 Dipeptides can result from reaction between A and S, depending on which COOH reacts with which NH 2 we get AS or SA The long, repetitive sequence of  N  CH  CO  atoms that make up a continuous chain is called the protein’s backbone Peptides are always written with the N-terminal amino acid (the one with the free  NH 2 group) on the left and the C- terminal amino acid (the one with the free  CO 2 H group) on the right Alanylserine is abbreviated Ala-Ser (or A-S), and serylalanine is abbreviated Ser-Ala (or S-A) Peptide Linkages

13 Protein Structure The primary structure of a protein is simply the amino acid sequence. The secondary structure of a protein describes how segments of the peptide backbone orient into a regular pattern. The tertiary structure describes how the entire protein molecule coils into an overall three- dimensional shape. The quaternary structure describes how different protein molecules come together to yield large aggregate structures

14 Primary Structure Primary structure influences shape in two main ways: o Allows hydrogen bonds to form between different amino acids along length of chain o Puts R groups in positions that allow them to interact

15 Secondary Structure Hydrogen bonds form between different parts of polypeptide chain These bonds give rise to coiled or extended pattern Helix or pleated sheet

16 Examples of Secondary Structure

17 heme group coiled and twisted polypeptide chain of one globin molecule Tertiary Structure Folding as a result of interactions between R groups

18 Hemoglobin Quaternary Structure Some proteins are made up of more than one polypeptide chain

19 Protein Shapes Fibrous proteins Polypeptide chains arranged as strands or sheets Globular proteins Polypeptide chains folded into compact, rounded shapes

Conformation of protein is an overall three dimensional structure of a protein i.e. a property of amino acid sequence Chaperones assist in the proper folding of proteins

21 Denaturation of Proteins The tertiary structure of a globular protein is the result of many intra-molecular attractions that can be disrupted by a change of the environment (temperature, pH etc.), causing the protein to become denatured Solubility is drastically decreased by heating (egg white, where the albumins unfold and coagulate) Enzymes also lose all catalytic activity when denatured

22 Disruption of three-dimensional shape Breakage of weak bonds Causes of denaturation: o pH o Temperature Destroying protein function Denaturation

Functions of Proteins I Catalysts and Metabolic Regulation – Enzymes Protection o Serum antifreeze proteins o Blood coagulation o Antibodies Membrane Transport – Nutrients Signal Transduction – Cell Surface Receptors Structural Support – Collagen

Functions of Proteins II Coordinated Motion – Muscle Contraction Genetic Regulation – DNA Binding Proteins Transport – Hemoglobin Generation and Transport of Nerve Impulses Nutrient Storage o Seed proteins o Casein in milk

Classification of Proteins Simple Proteins Conjugated Proteins Cofactors Prosthetic Groups Oligomeric Proteins (more than one polypeptide chain)

26 An enzyme is a protein that acts as a catalyst for a biological reaction. Most enzymes are specific for substrates while enzymes involved in digestion, such as papain attack many substrates Enzymes

27 Types of Enzymes by Function Enzymes are usually grouped according to the kind of reaction they catalyze, not by their structures

Cofactors In addition to the protein part, many enzymes also have a nonprotein part called a cofactor The protein part in such an enzyme is called an APOENZYME, and the combination of apoenzyme plus cofactor is called a HOLOENZYME. Only holoenzymes have biological activity; neither cofactor nor apoenzyme can catalyze reactions by themselves A cofactor can be either an inorganic ion or an organic molecule, called a COENZYME Many coenzymes are derived from vitamins, organic molecules that are dietary requirements for metabolism and/or growth.

Prosthetic GroupConjugated Protein Nucleic AcidNucleoprotein LipidLipoprotein PhosphatePhosphoprotein Metal Ion(s)Metalloprotein Polysaccharide(s)Glycoproteins Prosthetic Groups

Oligomeric Proteins (more than one polypeptide chain) Identical subunits Non-identical subunits Subunits held together by covalent or non- covalent linkages Covalent linkages are not peptide bonds

Aspects of Metabolism Metabolism: The life process. –Catabolism. Substances are broken down. –Anabolism. Substances are built up. Protein digestion: Stomach: HCl and pepsin hydrolize 10% of peptide bonds. Intestine: Trypsin and chymotrypsin cleave peptide fragments further.

32 Based on McMurry’s Organic Chemistry, 7 th edition