Chemistry of AAs and Proteins PDF

BCH 208 Chemistry of Amino Acids and Proteins Muhammad Hassan Yankuzo (MBBS, MSc, PhD)  Chemistry of Amino Acids Hydrolyzed products of protein. Organic compounds that naturally contain an amino (basic) group and a carboxylic (acidic) group. 20 L-α- amino acids...

BCH 208 Chemistry of Amino Acids and Proteins Muhammad Hassan Yankuzo (MBBS, MSc, PhD)  Chemistry of Amino Acids Hydrolyzed products of protein. Organic compounds that naturally contain an amino (basic) group and a carboxylic (acidic) group. 20 L-α- amino acids commonly exist in mammalian system.  Nomenclature of Amino acids Amino acids have two basic naming system: ❖Three letter word e.g. Ala, Val, Leu, Ile etc ❖One letter word e.g. A, V, L, I Classification of Amino Acids Amino acids are classified in different ways, as follows: According to the type of reaction of their R group According to the polarity of the side chain According to the nutritional requirement  Classification of Amino Acids: contnd According to the type of reaction of the R group Amino acids are classified as neutral Aas (e.g. Gly, Ala, Val, Leu, ILe) ± branched aliphatic side chain, acidic [monoamino dicarboxylic Aas (e.g. glutamic & aspartic Aas)], and basic Aas (e.g. lys Arg & His). According to the polarity of the side chain: Non polar/hyrophobic (e.g. Ala, Val, Leu, Ile), polar with non-charged R group (those having OH, SH & amide group), polar with +vely charged R group (e.g. Lys, Arg, His) and polar with negatively charged R group (e.g. Aspartic and glutamic acids) According to the nutritional requirement Aas are classified as essential and non essential Aas. NB: A & H are considered semi-essential Aas. Hydroxyl group containing Aas (e.g. Ser & Thr). They are important for the linkage of a protein with other compounds such as in the case of conjugated proteins. Based on metabolic fate of the carbon skeleton of Aas: glucogenic (gly, Ala, Asp, Met), Ketogenic (Leu, Lys) or both (Ile, Phe, Tyr & Trp). Sulphur containing Aas e.g. Cysteine (SH group) & Cystine (S-S group) as a result of condensation of the two Cysteine molecules. Properties of Amino acids All Aas (except glycine) possess optical isomerism due to the presence of asymmetric (chiral) carbon atom. Amino Acids exist as Zwitterions (dipolar ions) at physiological pH because they carry both negative and positive charges. Amino Acids behave as ampholytes since they can either donate a proton (COOH) OR accept a proton (NH2) at physiological pH. Polypeptides and proteins are formed from a string of amino acids joined together by peptide bonds. Following deamination, the carbon skeleton of the Amino acids can be used as a source of energy.  Isoelectric pH (PI) Amino acids rarely exist in a neutral form; at low pH, they exist as cations while at high pH they behave as anions. Isoelectric pH (PI) is a pH at which Amino acids carries both positive and negative charges, and thus exists as Zwitterion or dipolar ion. Such Aas are electrically neutral, with minimum solubility, maximum precipitability, and least buffering capacity. Each amino acid has a characteristic PI value which can be calculated by taking the average pKa values of the corresponding ionizable groups. For e.g. Leu has 2 ionizable groups (COOH & NH3) with pKa values of 2.4 and 9.6. Thus its calculated PI is 6.0  Isoelectric pH: continued The acidic and basic nature of Aas determines the PI of a protein. Acidic Aas (Glu, Asp) and basic Aas (Arg, His, Lys) strongly influence the PI, where proteins exist mainly as Zwitterion or dipolar ion. At a pH below the PI, some of the carboxylic acid group will be protonated, and the pH responsible for this protonation depends on the Ka of the COOH group which is typically between 1 – 3. Similarly at a pH above the PI, some of the ammonium group will be de-protonated, and the pH responsible for this de-protonation depends on the Ka of the NH2 group which is typically between 8 – 11. Concept of Zwitterion formation  Essential and Non-essential Amino Acids Essential (10) Non-essential – Arginine – Alanine – Histidine – Asparagine – Isoleucine – Aspartate – Leucine – Cysteine – Lysine – Glutamate – Methionine – Glutamine – Phenylalanine – Glycine – Threonine – Proline – Tryptophan – Serine – Valine – Tyrosine Remember: PVT TIM HALL NB: AH – Semi essential  Ten Essential amino acids 1. branched chain: Val, Leu, Ile 2. basic: His, Arg, Lys 3. aromatic: Phe (→ Tyr), Trp 4. sulfur-containing: Met (→ Cys) 5. Other: Thr NB: Characteristic indole ring Dibasic-monocarboxylic Aas Nonstandard Amino Acids  Seven degradation products of AAs 1.) pyruvate ← Gly, Ala, Ser, Thr, Cys, Trp 2.) oxaloacetate ← Asp, Asn 3.) α-ketoglutarate ← Glu, Gln, Pro, Arg, His 4.) succinyl-CoA ← Val, Ile, Met, Thr 5.) fumarate ← Phe, Tyr glucogenic AAs ketogenic Aas 6.) acetyl-CoA ← Ile Glucoketogenic AAs 7.) acetoacetyl-CoA ← Lys, Leu, Phe, Tyr, Trp CLASS EXERCISE  Proteins Proteins are polymers of L α-amino acids joined together by peptide bonds via condensation reaction. They are the most abundant organic molecules of life that perform both structural and dynamic functions in the living cells.  How is a peptide bond formed?  Steps of building a protein Specific Aas are transferred (by tRNA) to the mitochondria to connect to the growing peptide chain. The first peptide bond joins two Aas to form a dipeptide The second peptide bond joins three Aas to produce a tripeptide ----- the process continue in hundreds – polypeptide When the amino group of an AA combines with carboxyl group of another AA, a peptide bond is formed.  Structure of Proteins Primary Structure – Linear sequence of amino acids. Secondary Structure – Form helices or sheets due to their structure. Tertiary Structure – A folded protein. Quaternary Structure – 2 or more polypeptide chains bonded together.  Primary structure of proteins ▪ This consist of the linear sequence of amino acids that forms the backbone of all proteins (polypeptides) ▪ The unique sequence of Aas in each protein is determined by the DNA. The information from DNA is passed to the mRNA ▪ The polypeptides always begins with free N-terminal by the left and ends with free C-terminal by the right ▪ Most genetic diseases (e.g. SCDx) are due to the abnormalities associated with primary structure of proteins  Secondary structure of proteins ▪ The twisting or folding of polypeptide chains held close to each other by hydrogen bonds. α-Helix and β-pleated sheets are the two prototype secondary structures of proteins that have been identified ▪ α-Helix is a spiral structure with Aas side chains extending outward from the central axis. Each turn of α-Helix have 3.6 Aas, a distance of 0.54 nm, and a spacing of 0.15 nm b/w each AA ▪ β-sheets are formed by single or separate polypeptide chains arranged in either parallel or antiparallel direction, with additional H-bonds holding different segments of the polypeptide chains.  Tertiary structure of proteins ▪ A compact structure with hydrophobic side chains held in the interior and hydrophilic R groups on the surface of the protein molecule. Both covalent and noncovalent bonds contributes to ensure the protein stability. ▪ Peptide and disulfide bonds constitute the covalent bonds, while hydrogen bonds, hydrophobic and ionic interactions constitute the noncovalent bonds ▪ β-sheets are formed by single or separate polypeptide chains arranged in either parallel or antiparallel direction, with additional H-bonds holding different segments of the polypeptide chains.  Quaternary structure of proteins ▪ Comprises of two or more monomers of the polypeptide chains that may be identical or unrelated. They are stabilized by similar bonds as in the tertiary structure of proteins. Such proteins are called oligomers. ▪ Examples of oligomeric proteins are hemoglobin, lactate dehydrogenase and aspartate transcarbomylase. They play a vital role in the regulation of metabolism and cellular function. ▪ Ionic or electrostatic bonds are formed by the interaction between negatively charged groups of acidic Aas (COO) and positively charged groups (NH3) of basic Aas. Thank you