Amino Acids, Proteins & Polypeptides, Lecture notes of Biochemistry

Download Amino Acids, Proteins & Polypeptides and more Lecture notes Biochemistry in PDF only on Docsity! BSPH-2103 AMINO ACIDS PHARMACEUTICAL BIOCHEM Ma’am Patalinhug || September 2022 Transcribers: Gabrielle Martleah Mejares Liceo de Cagayan University-Paseo de Rio Campus-College of Pharmacy Page 1 of 6 AMINO ACIDS x Constitute the building blocks of proteins x 20 amino acids constitute the monomer units of proteins x Contain two functional groups: - Amino group (NH2) and a Carboxyl group (COOH) x 300 amino acids but there are 20 standard amino acids Basis to be considered for an Amino Acid 1. Will always have a Hydrogen attached to an alpha carbon (H) 2. Will have a carboxyl group (COOH) 3. Will have an amino acid (NH2) 4. Side chain (variable) 2 groups - which indicates the property of amino acids Classifications of Amino Acids 1. Structure - To classify the R group (variable side chain) 2. Side Chain Characters - Based in terms of Polarity; R group (Variable side chain) 3. Metabolic Fate - The 20 standard amino acids contains chemical reactions due to metabolism that forms both, or ƒ Glucose ƒ Acetyl COA/ Ketone bodies - Amino acids tend to form glucose= GLUCOGENIC - Amino acids tend to form ketone bodies= KETOGENIC 4. Nutritional Requirements a. Obtained in our diet = Essential A.A b. Also not obtained n our diet which is naturally synthesized = Non-Essential A.A c. Bases on age ƒ Children- essential ƒ Adults- Non Essential ƒ Children and Adults- Semi Essential BASED ON NUTRITIONAL REQUIREMENTS A. Essential Amino Acids - Threonine, Valine, Tryptophan, Isoleucine, Leucine, Lysine, Phenylalanine, Methionine, Histidine, Arginine B. Semi essential Amino Acids - Histidine, Arginine C. Non-essential Amino Acids - Alanine, Asparagine, Aspartic Acid, Cysteine, Glutamic Acid, Glutamine, Glycine, Proline, Serine, Tyrosine BASED ON STRUCTURE A. Aliphatic Amino Acids - Aliphatic means no ring; straight chain (C-C, C-H) ƒ 1 a COOH monocarboxylic ƒ 2 a COOH dicarboxylic B. Aromatic Amino Acids C. Heterocyclic Amino Acids D. Imino Acid E. Derived Amino Acid F. Special Groups A. Aliphatic Amino Acids 1. Mono amino mono carboxylic acids 1.1 Simple - Smaller groups - Glycine is the simplest A.A 1. Mono amino mono carboxylic acids 1.2 Branched Chain POLARITY 1. Non-Polar-Hydrophobic - Interior, A.A are hidden 2. Polar-Hydrophobic - Complexation occurs: proteins are found Exterior. a. Charged b. Uncharged PHARMACEUTICAL BIOCHEM LECTURE Page 2 of 6 ISOPROPYL ISOBUTYL SEC-BUTYL 1. Mono amino mono carboxylic acids 1.3 Hydroxyl HYDROMETHYL HYDROXYETHYL 1. Mono amino mono carboxylic acids 1.4 Sulfur-containing THIOMETHYL ETHYLMETHYL THIOETHER - If sulfur atm is existing use “-thio” as prefix 1. Mono amino mono carboxylic acids 1.5 Amino acid with amide group 2. Mono amino dicarboxylic acids B. Aromatic Amino Acids - Benzene Phenylated form of alanine Phenol- benzene with - oh Largest amino acid; Indule (whole ring of Tryptophan) C. Heterocyclic Amino Acids - Contains atoms other than Carbon - Hetero= two or more IMIDAZOLE; ring in Histidine INDULE; ring inside tryptophan D. Imino Acid - Carbon atoms attached to N - Imino are secondary structure of amine (2 C atoms) Pyrrolidine- ring structure attached to proline E. Derived Amino Acids 1. Derived amino acid found in protein - Important in synthesize of collagen Ex.- hydroxyproline - Hydroxylation of proline E. Derived Amino Acids PHARMACEUTICAL BIOCHEM LECTURE Page 5 of 6 Isoelectric point (pI) o pI is the pH at which AA will carry no charge (zwitterionic), all groups are ionized charges cancel each other o Midway between the pka values for ionization on either side of the isoelectric species For R = nonionizable side chain - neither donate nor accept proton - That’s why its charge is 0 Note: Average of the 2 pKa’s where : pK1 – given pKa of –COOH pK2 – given pKa of –NH2 Sidechain 1. Non-ionizable 2. Acidic 3. Basic Example: 1. Glyceine ƒ pK1= 2.34 and pK2 = 9.6 pI= 5.97 For R = acidic side chain (e.g. Glu and Asp) - 3 pka values are given - The lower the pka, the acidic the A.A is Note: Average of the ORZHUS.D¶V Where: pK1 – given pKa of –COOH pKR – given pKa of –acidic side chain Example: 1. Aspartic Acid (side chain of carboxyl group) ƒ pK1= 1.88; pK2 = 9.68; pK3 = 3.65 pI= 2.77 For R = basic side chain (e.g. His, Lys, Arg) - the higher the pka, h more basic the A.A is 1RWH$YHUDJHRIWKHKLJKHUS.D¶V Where: pKR – given pKa of basic side chain pK2 – given pKa of –NH2 Example 1. Histidine ƒ pK1= 1.88; pK2 = 6.00; pK3 = 9.68 pI= 7.84 SPECIFIC PROPERTY: Optical Property o Optical: the structure contains chiral carbon o Amino acids are chiral, the tetrahedral C with different substituents o Chirality: describes the handedness of a molecule o Refers to its ability to rotate a plane polarized light a.) D: right, Dextrorotatory/Dextroisomer - synthetic - clockwise b.) L: left, Levorotatory/Levoisomer - counterclockwise - Naturally occurring o Chiral Atom= 4 surrounding atoms are different o Generally, amino acids are chiral, except glycine. o Therefore, Glycine is not an Optical Property and does not possess the Chiral property o The position of the amino group on the left or right side of the alpha-carbon determines the L or D configuration. o Aromatic R groups in AA absorb UV light with maximum absorbance in range of 280nm. (Phenylalanine, Tyrosine, Tryptophan) o Ability of protein to absorb UV light due to the presence of tryptophan (pre-dominant) __________________________________________________ AMINO ACIDS: SPECIAL FUNCTIONS 1. GABA from glutamic acid and dopamine from tyrosine – neurotransmitters 2. Thyroxine – thyroid hormone 3. Histidine – buffering activity; found in reactive center of enzymes; can donate and accept electrons 4. Lysine – binding of coenzymes like pyridoxal phosphate and biotin 5. Ornithine and citrulline derived from arginine – essential in urea synthesis PHARMACEUTICAL BIOCHEM LECTURE Page 6 of 6 PEPTIDES o A.A undergo polymerization through dehydration = peptide (2-10 A.A) to protein (40 plus A.A; macromolecule) o Are formed when amino acids are joined together by amide bonds (C-NH) o Residue (aka: Moiety) – each amino acid component o Also called the amide bond o Formed when alpha carboxyl group of one amino acid reacts with alpha amino group of another amino acid with loss of water o CO – NH bridge a. N-terminal= the residue; carrying the free amino group - any amino chain will carry a full amino group (N- TERMINOUS) b. C-terminal= residue carrying the carboxyl group - free carboxyl group (C-TERMINOUS) _______________________________________________ The amino acids Ala and Ser can combine in this way: Or they two can combine with Ser first and Ala second o The amino acids with free –NH3+ group is the N-terminal amino acid and is written on the left. o The amino acid with the free –COO- group is the C-terminal amino acid and it is written on the right. NAMING A PEPTIDE CHAIN o Amino acid name ending in –in, -ine, -ic, -an, and –ate o Changed to –yl except the C-terminal o Tri-, or octa- refers to the number of residues, not the number of bonds o ULTIMATE: the last A.A ; retain the name of A.A o TO THE LEFT: ending in -yl SMALL PEPTIDES WITH PHYSIOLOGICAL ACTIVITY & THERAPEUTIC USE 1. Carnosine– dipeptide; found in muscle tissue 2. Glutathione – tripeptide; scavenger for oxidizing agents 3. Enkephalins – pentapeptide; Leu & Met enkephalins 4. Oxytocin & Vasopressin – peptides with cyclic structure containing 9 amino acid residues 5. Gramicidin S and Tyrocidine A– peptides with 10 amino acid residues REACTING GROUP (CARBOXYL GROUP) REACTING GROUP (AMINO GROUP) DEHYDRATION PROCESS FREE CARBOXYL GROUP FREE AMINO GROUP