استاذ الكيمياءالحيوية

Transcription

1 قسم الكيمياء الحيوية د.دولت على سالمه استاذ الكيمياءالحيوية ٢٠١٥-٢٠١٤ الرمز الكودي : ٥١٢ المحاضرة األولى ١

2 Content : Definition of proteins Definition of amino acids Definition of peptide bond General structure of amino acids Numbering of amino acids Nomenclature of amino acids. Classification of amino acids. Biological importance of amino acid derivatives 2

3 What Are Proteins? Proteins are chains of amino acids folded into compact shapes Large molecules Made up of chains of amino acids Are found in every cell in the body Are involved in most of the body s functions and life processes The sequence of amino acids is determined by DNA 3

4 What Are Proteins? Are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form in a biologically i ll functional way. 4

5 Structure of Proteins Made up of chains of amino acids; classified by number of amino acids in a chain Peptides: fewer than 50 amino acids Dipeptides: 2 amino acids Tripeptides: 3 amino acids Polypeptides: more than 10 amino acids Proteins: more than 50 amino acids Typically 100 to 10, amino acids linked together Chains are synthesizes based on specific bodily DNA This primary structure is determined from the genetic information encoded in DNA. Amino acids are composed of carbon, hydrogen, oxygen, and nitrogen 5

6 Number, Types and Sequence of amino acids determine the protein 6 amino acids 5 amino acids 6 amino acids but in a different sequence 7 amino acids 6

7 Definition of Amino acids Amino acids are a group of organic compounds containing two functional groups amino and carboxyl. The amino group ( -NH2) is basic while the carboxyl group ( - COOH ) is acidic in nature There are about 300 amino acids occur in nature. Only L-α-20 of them occur in proteins. 7

8 Amino Acids Phenylalanine Cysteine Glycine Alanine Vli Valine l S CH H H 3 H H R H H 3 C C Amino H N C C H H O O H Acid 8

9 Each amino acid has 4 different groups attached to α- carbon ( which is C-atom next to COOH). These 4 groups are : amino group, COOH gp, Hydrogen atom and side Chain (R) H NH 3 + C COO - R Sometimes books give this [amino acid in solution] 9

10 Polarity: the degree to which Amino Acid electrons are distributed asymmetrically Charge: the ability to gain or lose an electron pk value: tendency of Amino Acid to ionize (related to ph where half Amino Acid are ionized) pka = ph when ½ of an available amount of an ionizable group is ionized Aliphatic vs. aromatic sidechains Hydrophobicity: tendency to hide from water molecules Interesting AA: methionine (start signal), histidine (often active site of enzyme) ١٠

11 At physiological PH (7.4), -COOH gp is dissociated forming a negatively charged carboxylate ion (COO-). And amino gp is protonated forming positively charged ion (NH3+) forming Zwitter ion 11

12 H 2 N Amino acids are joined together by a condensation reaction Carboxyl Amino group group H O H H O H H H O O C C + N C C H 2 N C C N C C OH H OH OH H CH H CH 3 3 H 2 O 2 Peptide bond A peptide bondis a covalent C N bondformed by condensation between the NH 2 of one aminoacid acid and COOH of another 12

13 Amino acid carbons are named in sequence using the Greek alphabet (,,,, ) starting at the carbon between the carboxyl and amino groups. H 3 N COO CH CH 2 CH 2 CH 2 CH 2 NH 3 13

14 Each amino acid has three letter (code) and one letter (Symbol) abbreviations- Examples- 1) Unique first letter Cysteine Cysteine- Cys- C Histidine- His- H 2) Priority of commonly occurring amino acids Alanine-Ala-A (Preference over Aspartate) Glycine- Gly-G G (Preference over Glutamate) 14

15 3) Similar sounding names- Some one letter symbols sound like the amino acids they represent- Example Tryptophan W (Twyptophan) Phenyl alanine F 4) Letters close to initial letter Aspartate- Asx - B ( near A) Lysine Lys - K (near L ) 15

16 Amino acid abbreviations 16

17 Classify the amino acids in two different ways. 17

18 1-Based on structure 2-Based on side chain 3-Based on metabolic fate 4-Based on nutritional requirement 5-based on Physical Properties 18

19 1) Based on structure: 19

20 Aliphatic amino acids Monoamino monocarboxylic acids Monoamino dicarboxylic acids Dibasic monocarboxylic acids 20

21 Aromatic (R) Groups Their aromatic side chains, are nonpolar so that participate in hydrophobic interactions. Tyrosine is an important in some enzymes. Most proteins absorb light at a wavelength of 280 nm due to aromatic groups. A property exploited by researchers in the characterization of proteins. -21

22 2) Based on side chain General categories of -amino acids (based on the polarity: (that is, the distribution of electric chargel) 22

23 Non-polar amino acids An amino acid is nonpolar when the R group is H, alkyl, or aromatic. 23

24 Polar, non-charged amino acids An amino acid is polar when the R group is an alcohol, thiol, or amide sulfhydryl l group 24

25 Polar, non-charged amino acids More hydrophilic because they form hydrogen bonds with water. includes serine, threonine, cysteine, asparagine, and glutamine. Cysteine contains a sulfhydryl group (-SH), an important component of the active site of many enzymes. Two cysteine can become oxidized to form a dimmer cystine, which contains a covalent cross- link called a disulfide bond (-S-S-). ). 25

26 Uncharged polar side chains(con.) Serine and threonine contain a polar hydroxyl group. Serve as a site of attachment (in enzymes) for groups such as a phosphate. Amide group of asparagine, as well as the hydroxyl group of serine or threonine serve as a site of attachment for oligosaccharide chains in glycoproteins. 26

27 Negatively-charged amino acids 27

28 Positively-charged amino acids 28

29 3) Classification based on metabolic fate The carbon skeleton of amino acids can be used either for glucose production or for the production of ketone bodies, Based on that : Both glucogenic g and ketogenic amino acids: Isoleucine, Tyrosine, Phenylalanine and Tryptophan Purely Ketogenic amino acids: Leucine and Lysine Purely Glucogenic amino acids: The remaining 14 amino acids are glucogenic. Alanine, valine,serine, threonine, glycine, methionine, asparagine, glutamine, cysteine, cystine, aspartic acid, glutamic acid, histidine and arginine. 29

30 Essential amino acids: These amino acids cannot be synthesized in the body and have to be present essentially in the diet. Examples- Valine, Isoleucine, Leucine, Lysine, Methionine, Threonine, Tryptophan and Phenylalanine Semi-essential essential amino acids: These amino acids can be synthesized in the body but the rate of synthesis is lesser than the requirement(e.g. during growth, repair or pregnancy) Examples-Arginine and Histidine. Non-essential amino acids: These amino acids are synthesized in the body, thus their absence in the diet does not adversely affect the growth. Examples- Glycine, Alanine, and the other remaining i amino acids. 30

31 Essential AA Histidine Nonessential AA Alanine Isoleucine Arginine ** Leucine Asparagine Lysine Aspartic Acid Methionine Cysteine ** Phenylalanine Glutamic acid Threonine Glutamine ** Tryptophan Glycine ** Valine Proline ** Serine Tyrosine ** 31

32 5)Classification based on Physical Properties Amino Acids Hydrophilic aa Hydrophobic aa Special aa Basic side chain aa Arg, Lys, His Aliphatic Side Chain aa Ala, Val, Leu, Ile Gly, Cys, Pro Acidic side chain aa Asp, Glu Polar, uncharged side chain aa Ser, Thr, Asn, Gln Aromatic Side Chain aa Phe, Tyr, Trp Met Hydrophobicity comes from the greek word Hydro(water) and Phobicity (fear) it refers to the physical property of a material that repels amassof water. 32

33 Special groups in amino acids Arginine- i Guanidinium i group Phenyl Alanine- Benzene group Tyrosine- Phenol group Tryptophan- Indole group Histidine- Imidazole group Proline Proline- Pyrrolidine Proline has a secondary amino group, hence it is an imino acid. Proline gives the fibrous structure of collagen, and interrupts the α-helices found in globular proteins. 33

34 Why do amino acids differ in their chemical and physical properties (size, water solubility, electrical charge)? Because of their different R groups 34

35 35

36 Non standard amino acids Amino acids can be classed as : standard amino acids and non standard amino acids. Of 300 amino acids human body codes 20 amino acids. Aside from the 20 standard amino acids, there are many other amino acids that are called non proteinogenic or non standard. They are either not found in proteins (for example Ornithine, GABA), or are not produced directly. Non standard amino acids that are found in proteins are formed by post translational translational modification, which is modification after translation during protein synthesis. 36

37 Special functions of Amino acids Incorporated in to tissue proteins Niacin, Serotonin and melatonin are synthesized from Tryptophan Melanin, thyroid hormone, catecholamines are synthesized from Tyrosine γ - carboxy-glutamate is found in blood-clotting proteins GABA (γ- amino butyric acid) (neurotransmitter) is synthesized from Glutamic acid Nitric oxide, a smooth muscle relaxant is synthesized from Arginine. Act as precursors for haem, creatine and glutathione,, Porphyrins, py purines and pyrimidines. 37

38 Biological importance of amino acid derivatives Derived amino acid found in proteins: 5-Hydroxylysine yy and hydroxyproline yp are found in connective-tissue tissue proteins such as collagen. Derived amino acid not found in proteins Ornithine and citrulline (occur in the urea cycle). Non alpha amino acids: GABA( GABA(Derivative of glutamic acid ( (is the chief inhibitory neurotransmitter in the mammalian central nervous system., β-alanine. -38

39 Thyroxin and 3,3`, `,5-triiodothyronine (An thyroid hormone ), iodinated tyrosine are found in thyroglobulin, a protein produced by the thyroid gland. Cycloserine: Derivative of serine -As an antituberculous مضاد التدرنdrug Hitamine : Synthesized from histidine. - Mediator in allergic reactions. epinephrine, histamine, serotonin act as neurotransmitters and hormones 39

40 Biologically Active Amino Acids -Each derived from a common amino acid by a modification and are found in only a few connective tissues such as collagen. is found only in the thyroid gland -Remember, amino acids without charged groups on side chain exist in neutral solution as _... with no net charge 27-40

41 THANK YOU