Biochemistry Lectures on Lippincott PDF

1 BIOCHEMISRTY DR FAWZY Lectures on Lippincott Biochemistry 2 What is biochemistry 3  Biochemistry, sometimes called biological chemistry, is the study of chemical processes taking place in living organisms. What is biochemi...

1 BIOCHEMISRTY DR FAWZY Lectures on Lippincott Biochemistry 2 What is biochemistry 3  Biochemistry, sometimes called biological chemistry, is the study of chemical processes taking place in living organisms. What is biochemistry Classes 4  Amino Acids definition and function Amino acids :are biologically important organic compounds containing amine (-NH2) and carboxylic acid (- COOH) groups, along with a side chain (R functional group) specific to each amino acid. Functions: 1- Building units of the peptides and proteins. 2- Transfer of nitrogen (formation of New AA, RNA, DNA, and urea). 3- Control the rate of protein turnover and signal transduction (alanine affects glycolysis rate). 4-Synthesis of neurotransmitters such as epinephrine. 5- Detoxication (conversion of non-soluble toxin into soluble derivatives).6- Buffering action. 7- Energy production. 5  II. STRUCTURE OF THE AMINO ACIDS There are about 300 amino acids occur in nature. Only 20 of them occur in proteins. Each amino acid has a carboxyl group, a primary amino group(except for proline), and a distinctive side chain (“R-group”) bonded to the α-carbon atom. 6  II. STRUCTURE OF THE AMINO ACIDS At physiologic pH (≈ pH 7.4), the free AA forms negatively charged carboxylate ion (–COO–), and the amino group is protonated (–NH3+). In proteins, most carboxyl and amino groups form peptide bond which , are not available for chemical reaction except for hydrogen bonding. Thus, the nature of the side chains dictates the amino acid role in protein. So AA classified according to the side chains properties. 7  Classification basis 1-Chemical classification(side chains classification chemistry ) 2-Optical (D and L isomers) 3-Nutritional (essential, semi essential and non-essential) 4-Metabolic fate(glucogenic, ketogenic and mixed) 8 Amino acids classification to side chain chemistry A. Amino acids with nonpolar side chains(R-groups) B. Amino acids with uncharged polar side chains C. Amino acids with acidic side chains D. Amino acids with basic side chains 9  II. STRUCTURE OF THE AMINO ACIDS A. Amino acids with nonpolar side chains(R-groups) AA has a nonpolar side chain that does not gain or lose protons or participate in hydrogen or ionic bonds→ hydrophobic interactions. 1. Location of nonpolar amino acids in proteins: In aqueous environment––the nonpolar side chains amino acids tend to cluster in the interior of the protein → forming its three- dimensional shape. 10  II. STRUCTURE OF THE AMINO ACIDS A. Amino acids with nonpolar side chains 1. Location of nonpolar amino acids in proteins: In a hydrophobic environment, such as a membrane, the nonpolar R-groups are found on the outside surface of the protein (i.e. R-groups are oriented towards the lipid membrane)→stabilize protein structure. 11 12  II. STRUCTURE OF THE AMINO ACIDS A. Amino acids with nonpolar side chains 2. Proline : Proline side chain has a rigid structure ( containing 2ry amino group in ring) → formation of the rigid fibrous structure of collagen ,and often interrupts the α- helices of globular proteins. Primary amino acid 13  II. STRUCTURE OF THE AMINO ACIDS B. Amino acids with uncharged polar side chains AA contain polar atoms (S, N. O) with zero net charge at neutral pH. The side chains of asparagine, glutamine Serine, threonine, and tyrosine each contain a polar hydroxyl or carbonyl group → hydrogen bonding (while cysteine contains S). 14 15  II. STRUCTURE OF THE AMINO ACIDS B. Amino acids with uncharged polar 1.side chainsbond: Disulfide s Cy teine contains (–SH) group, the active site of many enzymes. In proteins, the –SH groups of two cysteines oxidatively united to form a dimer, cystine. Disulfide bonds stabilize proteins such as Albumin. 2. Side chains as sites of attachment for other compounds: (OH)serine and threonine →attachment for16  II. STRUCTURE OF THE AMINO ACIDS C. Amino acids with acidic side chains Aspartic and Glutamic acid are proton donors. side chains, containing a negatively charged carboxylate group (–COO–). Glutamic 17  II. STRUCTURE OF THE AMINO ACIDS D. Amino acids with basic side chains Side chains of lysine and arginine as proton acceptor are fully ionized and positively charged. Histidine is weakly basic, depending on the ionic environment provided by the polypeptide chains. 18 Another AA classification according to side chain 1-neutral AA: 1 amino gp + 1 COOH gp a- non polar R b- polar R 2-acidic AA: 1 amino gp + 2 COOH gp 3-basic AA: 2 amino gp + 1 COOH gp 19  III. ACIDIC AND BASIC PROPERTIES OF AMINO ACIDS Both free amino acids and some amino acids combined in peptide can act as buffers→ regulation of body pH. B. Buffers: Solution that resists change in pH, which consist of weak acid and its salt or weak base and its salt. p[H+] of the buffer calculated by: Henderson- Hassel Balch equation:, where pH = log 1/[H+] or –log [H+]. 20  Acids , bases and buffers AA (act as both acid and base). i.e. at acidic pH, like a base accept H+ and at basic pH, like an acid accept OH-. A weak acid is an acid that dissociates incompletely, releasing some of its hydrogen ions into the solution. a weak base : defined as a chemical base in which protonation is incomplete. A conjugate base is merely what is left after an acid has donated a proton in a chemical reaction. 21  III. ACIDIC AND BASIC PROPERTIES OF AMINO ACIDS Zwitterion : is a neutral molecule with positive charges equal to negative charges. Isoelectric point (PI): pH at which positive charges equal to negative charges that the(net) charge is zero. 22  III. ACIDIC AND BASIC PROPERTIES OF AMINO ACIDS C. Titration of an amino acid Electrophoresis Separation of plasma proteins The negatively charged proteins move toward the positive electrode( anode ) at a rate determined by their net negative charge. Variations in the mobility pattern are suggestive of certain diseases. Basic AA : are closer to cathode(Arg, Lys and His). Acidic AA : are closer to anode(Asp and Glu). 23  Nutritional classification of(10) Nonessential AA: AAAA can be synthesized in the body. Essential AA : (8) AA can not be synthesized and must be supplied in the diet. Semiessential: (2) AA cannot be fully synthesized semiessential essentialin: childhood Non essential contain ing Valine, Leucine, Glycine, Alanine isoleucine threonine serine OH methionine Cysteine SH Tryptophan, Tyrosine Aromati ,Phenylalanine cR proline 2ry 24 imino R  Essential AA To Libya left I Tryptopha Lysine Leucine Isoleucin n e Philippine Through Visit Make Phenyl Threoni Valine Methioni alanine ne ne  F. Optical classification properties of the amino acids Enantiomers : isomers that are mirror images to each other with chiral (asymmetric carbon) center. (Optically active compounds i.e. have D and L forms) Glycine is optically inactive with no D and L forms. Human amino acids are of the L-configuration. D-amino acids are found in some antibiotics and in plant cell walls. Pt definition: are linear polymers of L-α amino acids linked together by peptide.bond 26  Metabolic classification of AA(Fate): A- Ketogenic amino acid (L,L):Leucine and Lysine : AA forming ketone bodies. B- Mixed fate AA: AAs which produce Glucose and ketone bodies.(Isoleucine, threonine, phenylalanine, tryptophan and tyrosine). C- Glucogenic AA: AAs which produce Glucose only (the rest of AA). 27  SUMMARY Each amino acid has an -carboxyl group and a primary amino group (except for proline, which has a secondary amino group). At physiologic pH, the α-carboxyl group is dissociated, forming the negatively charged carboxylate ion (– COO–), and the α-amino group is protonated (–NH3+). Each amino acid also contains one of 20 distinctive side chains attached to the α-carbon atom. The chemical nature of this side chain determines the function of AA in a protein, and provides the basis for classification of the AAs as nonpolar, uncharged polar, acidic, or basic. 28  Summary All free amino acids, plus charged amino acids in peptide chains, can serve as buffers. The α-carbon of each amino acid (except glycine) is attached to four different chemical groups and is, therefore, a chiral or optically active carbon atom. Only the L-form of amino acids is found in proteins synthesized by the human body. 29