Amino Acids االحماض األمينية

Transcription

1 Amino Acids االحماض األمينية Presented by Dr. Mohammad Saadeh The requirements for the Pharmaceutical Biochemistry I Philadelphia University Faculty of pharmacy

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3 Cell Structure

4 Amino Acids The study of proteins has occupied biochemists to understand three dimensional shapes, and chemical activities of proteins may be key to the most scientific challenge. 1. Thermophilic bacteria thrive at high temperatures. What is the different about the proteins? 2. HIV-1 associated with AIDS.

5 The most important biological function of proteins 1. Many proteins function as enzymes, the biochemical catalysts. 2. Proteins bind other molecules for storage and transport, myoglobin and hemoglobin 3. Protein such as tubulin, actin, and collagen, provide support and shape to cells. 4. Proteins can do mechanicals work, movement of flagella, separation chromosome at mitosis, contraction of muscles. 5. Proteins play decoding information in the cell, translation, regulating gene expression. 6. Proteins are hormones, which regulate biochemical activity in target cells or tissues. 7. Proteins have highly specialized functions, Antibody, and toxin.

6 I. General structure of Amino acids About 300 a.a have been found in nature but all organisms use the same 20 a.a as building blocks for the assembly of protein molecules. These 20 a.a are called the common or standard a.a. Enormous variety of different polypeptides can be produced by connecting the 20 standard a.a in various combinations.

7 I. General structure of Amino acids An a.a is a compound that contains both a carboxyl (-COOH) and amino (-NH 2 ) group as part of its structure. In the 20 standard a.a that make up proteins, the carboxyl and amino groups are bonded to the same carbon atom, called α -carbon. In addition, the amino acids in proteins contain side chains that determine their role in the proteins behavior.

8 I. General structure of Amino acids Pka 9 dipolar ions Pka 3 Inside the cell, under normal physiological condition PH The amino group are protonated (-NH 3+ ), Pka 9 Carboxyl is ionize (-coo - ), Pka 3. So amino acid are zwitterions or dipolar ions, even though their net charge may be zero.

9 I. General structure of Amino acids All 20 standard a.a except glycine is achiral, the α-carbon is chiral or asymmetric, since it has 4 different group bonded to it. Amino acid steroisomers are nonsuperimposable mirror image so it called enantiomers such as L and D isomers. Both L &D a.a are found in nature. Protein contain only L-a.a. but in bacteria D-a.a occur in bacterial cell walls and antibiotic of bacterial origin. enantiomers

10 In fischer projection of a.a, horizontal bonds at a chiral center extend toward the viewer, and vertical bonds extend away. The properties of the side chains greatly influence the overall three- dimentional shape.

11 The RS system of configuration

12 1. Aliphatic R groups Glycine is the smallest a.a, R group is hydrogen atom, so it has little hydrophobic character to the molecule. α-carbon is not chiral (achiral). Glycine play a unique in structure of many proteins because the side chain is small enough to fit into niches that can accommodate no other a.a. Glycine[G] (Gly)

13 1. Aliphatic R groups Alanine(Ala,A), Valine(Val,V), Leucine(Leu,L) and Isoleucine(Ile,I), have saturated side chains. Isoleucine, two carbon α&β are chiral so it have (2 2 =4) stereoisomers (L&D. Isoleucine and L&D. alloisoleucine). Alanine, Valine, Leucine, Isoleucine are important in establishing and maintaining the three-dimensional structures because their cluster away from water. Valine, Leucine, Isoleucine are branched side chain, All three a.a are highly hydrophobic.

14 1. Aliphatic R groups Proline(Pro,P) differ from the other 19 a.a Three carbon side chain is bonded to the nitrogen of its α-amino group, the α-carbon creating a cyclic molecule. The heterocyclic pyrrolidine ring of proline restrict the geometry of polypeptide, sometimes introducing abrupt changes in direction of the peptide chain. Cyclic structure of proline makes it much less hydrophobic than valine, leucine, isoleucine.

15 2. Aromatic R groups Phenylalanine (phe,f),tyrosine (Tyr,Y), Tryptophan (Trp, W) have side chains with aromatic groups. Phenylalanin has a hydrophobic benzyle side chain,tyrosine has phenol group, Tryptophan contain bicyclic indol group. Tyrosine(Tyr,Y), Tryptophan are not hydrophobic as Phenylalanine because the side chains include polar groups

16 2. Aromatic R groups All three aromatic a.a absorbe U.V because it contain delocalized π electron. At neutral PH, both tryptophan and tyrosine absorbe light at 280nm. Phenylalanine is almost transport at 280nm and absorbed light weakly at 260nm. Absorbance at 280 nm is used to estimate the concentration Of proteins in solutions. Absorbance four times of tyrosine. Absorption of light for tryptophan and tyrosine at ph6

17 3. Sulfur containing R groups Methionine (Met, M), contain non polar thioether group, it one of more hydrophobic a.a. and play an important role in synthesis of protein, it is the first a.a in polypeptide chain. Cysteine(Cys, C), side chain somewhat hydrophobic and highly reactive. The sulfhydryl group of Cysteine form weak H- bonds with O, N. sulfhydryl group is weak acid, its lose proton to be come negative charge thiolate ion. Methionine Cysteine

18 3. Sulfur containing R groups Cysteine don t have to be close together in amino acid sequence of the polypeptide chain they found in different chains. Disulfide bond, stabilize the threedimentional structures of some peptide by covalently cross linking cysteine residues in peptide chains. Inside the cell protein don t contain disulfide bond because the condition not fever oxidation. However, many secreted extracellular protein contain disulfide bridge. The two Cysteine adjacent in three dimention space to form disulfide bond Oxidation at slightly alkaline ph, because sulfhydryl groups are ionized at low ph.

19 4. Side chains with alcohol groups Serine and threonine have uncharged polar side chains (β-hydroxyl groups). These give hydrophilic character to aliphatic side chains. The hydroxyl groups of Serine and threonine have the weak ionization properties of primary and secondary alcohols. The hydroxymethyl group of serine dose not appreciably ionized in aqueous solution; nevertheless, this alcohol can react with active site of No. of enzymes as thought it were ionized. Threonine has two chiral carbon so it have (2 2 =4) stereoisomers (L&D. threonine and L&D. allothreonine ). (L-threonine in protein) Serine (Ser, S) Threonine (Thr, T)

20 5. Basic R groups Histidine (His, H), Lysine (Lys, k), and arginine (Arg,R) have hydrophilic side chains that are nitrogenous bases and are positively charged at ph 7. Second primary amino group at e position Charged guanidino group Imidazole group The side chain of histidine contains an imidazole ring substituent. The protonated from of this ring side chain is called an imidazolium ion.

21 5. Basic R groups Lysine is diamino acid, having both α and ε as an alkylammonium ion (-CH 2 NH 3+ ) at neutral ph and confers a positive charge in proteins. Second primary amin group at e position Arginine is the most basic acid of the 20 a.a its side chain guanidinium ion is protonated under all conditions normally found within a cell. (Arginine side chains also contribute positive charges in proteins). Charged guanidino group

22 6. Acidic R groups and their amide derivatives Aspartate(Asp, D) and glutamate (Glu, E) [aspartic acid or glutamic acid] are dicarboxilic and have negative charged hydrophilic side chain at ph 7 (ionized). Monosodium glutamate (MSG), which is used in food as flavoue enhancer. Carboxyl side chain

23 6. Acidic R groups and their amide derivatives Asparagine(Asn, N) and glutamine (Gln, Q) are amides of aspartic acid or glutamic acid The side chains of Asparagine and glutamine are uncharged, highly polar and found on the surface on proteins, where they can interact with the water molecules. The polar amide groups of Asparagine and glutamine can form H-bonds with side chains of other polar a.a. amide side chains

24 7. The hydrophobicity of amino acid side chains The relative hydrophobicity or hydrophilicity of each a.a is called hydropathy There are measuring hydropathy according the tendency of an amino acid to prefer a hydrophobic to hydrophilic environment. In some scales tryptophan has a much lower hydropathy value

25 7. The hydrophobicity of amino acid side chains Hydropathy is important in protein chain folding because hydrophobic side chains to be clustered in the interior of a protein and hydrophilic residue are usually found on the surface. Hydropathy used to predict which segments of membrane-spanning proteins are likely to be embedded in hdrophobic lipid bilayer.

26 III. Other amino acids and amino acid derivatives More than 200 different a.a are found in living organisms. S-Adenosylmethionine, methyl doner. Many species of bacteria & fungai synthesized D-amino acids that are used in cell walls & antibiotic (actionomycin). In the mammalian brain, glutamate is converted to the neurotansmitter γ-aminobutyrate (GABA). Histamine is synthesized mammals from histidine, to controls the constriction of certain blood vessels and secretion of HCL by stomach.

27 III. Other amino acids and amino acid derivatives Tyrosine is metabolized to epinephrine (adrenaline). Hormons that are regulate metabolism in mammals. Tyrosine is the precursor of the thyroid hormones thyroxin. Small amount of sodium iodide prevent goiter (hypothyroidism) caused by lack of iodide in the diet. Some amino acids are chemically modified after incorporated into polypeptides. Ex., proline residue in collagen are oxidized to form hydroxyproline residue.

28 III. Other amino acids and amino acid derivatives Glycosylation process that is addition carbohydrate to molecules such as proteins. Many protein are phosphorylated by the addition of phosphoryl groups to the side chains of, serine, threonine or tyrosine. the oxidation of cysteine residue to form cystine occurs after a polypeptide synthesized. 21 st a.a, selenocysteine is found from serine during protein synthesis and it is incorporated into a few proteins in a wide variety of species. 22 nd a.a is pyrrolysine, found in some species of archae bacteria. Pyrrolysine modified from lysine that is synthesized after being added to a growing peptide by the translation

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