Chapter 4: Amino Acids

Transcription

1 Chapter 4: Amino Acids All peptides and polypeptides are polymers of alpha-amino acids. lipid polysaccharide enzyme 1940s 1980s. Lipids membrane 1960s. Polysaccharide Are energy metabolites and many of them are essential nutrients. Several of the amino acids found in proteins also serve functions distinct from the formation of peptides and proteins, e.g., tyrosine in the formation of thyroid hormones or glutamate acting as a neurotransmitter. Epinephrine Tryptophan Dopamine Tyrosin General Features of Amino Acids -amino acids in peptides and proteins (excluding proline) consist of a carboxylic acid (-COOH) and an amino (-NH 2 ) functional group attached to the same tetrahedral carbon atom. Distinct R-groups, that distinguish one amino acid from another, also are attached to the alpha-carbon (except in the case of glycine where the R-group is hydrogen). The fourth substitution on the tetrahedral a-carbon of amino acids is hydrogen. In physiological condition, both the carboxylic acid and the amino groups of a-amino acids are completely ionized. pk 1 a-carboxylic acid, 2.2 pk 2 a-amino group, 9.4 pk R functional group ampholytes (amphoteric property)

2 Physical Properties Similar to ionic compound because of charged groups of opposite polarity.( zwitterions dipolar ions) The melting point of most amino acids are near 300 ºC More soluble in polar solvents (H 2 O etc.) At ph 7.0, both carboxyl and amino group are completely ionized. There are 20 Amino Acids encoded by codons in the genetic code. Peptide Bonds Peptide bond formation is a condensation reaction leading to the polymerization of amino acids into peptides and proteins. (Peptide: hormones, neurotransmitters, several antibiotics and antitumor agents) The presence of the carbonyl group in a peptide bond allows electron resonance stabilization to occur such that the peptide bond exhibits rigidity not unlike the typical - C=C- double bond. The peptide bond is, therefore, said to have partial double-bond character.

3 Amino Acid Structure/Function These 20 AAs can be divided into the above 3 groups (non-polar, flexible and polar)and then subdivided by their chemical character. I prefer to divide them based on the R-functional group. Aliphatic: Gly, Ala, Val, Leu, Ile, Pro Aromatic: Phe, Tyr, Trp Polar but uncharged: Ser, Thr, Asn, Gln Sulfur containing: Cys, Met Charged: Asp, Glu, His, Lys, Arg Amino Acid: Aliphatic-R Group Gly, Ala, Val, Leu, Ile, Pro Refer to the structure

4 Amino Acid: Aromatic R-Group Phe, Tyr, Trp Refer to the structure The aromatic R-groups in amino acids absorb ultraviolet light with an absorbance maximum in the range of 280nm. The ability of proteins to absorb ultraviolet light is predominantly due to the presence of the tryptophan which strongly absorbs ultraviolet light. Amino Acid: Polar but uncharged Ser, Thr, Asn, Gln Refer to the structure

5 Amino Acid: Sulfur containing Cys, Met Refer to the structure Amino Acid: Charged R-Group Asp, Glu, His, Lys, Arg Refer to the structure

6 Hydroxylysine, hydroxyproline - collagen Carboxyglutamate - bloodclotting proteins Pyroglutamate bacteriorhodopsin Phosphorylated amino acids - signaling device Uncommon amino acids Other uncommon amino acids

7 Reactions of Amino acids Carboxyl groups form amides & esters Amino groups form Schiff bases and amides Side chains show unique reactivities Cys residues can form disulfides and can be easily alkylated Few reactions are specific to a single kind of side chain Optical Properties of the Amino Acids A tetrahedral carbon atom with 4 distinct constituents is said to be chiral. Chirality: Describe the mirror images of a molecule are not superimposable. These molecules are designated as enantiomers of one another. ( superimposable ) ( optical isomers )

8 Optical Activity The handedness of a chiral molecule is observable by the ability of a molecule to rotate the plane of polarized light either to the right (dextrorotatory, + or d) or to the left (levorotatory, - or l ). 25 observed rotation (degree) [ ] D -3 optical path length (dm) X conc.(g.cm ) The physical and chemical properties of optical isomers are almost identical except for the optical activity. Polarimeter is used to measure the specific rotation of optical isomer Why L- -amino acids? All of the amino acids in proteins exhibit the same absolute steric configuration as L-glyceraldehyde. Therefore, they are all L- -amino acids. hydroxyl, aldehyde, CH2OH amino, carboxyl, R D-amino acids are never found in proteins, although they exist in nature. D-amino acids are often found in polypeptide antibiotics.

9 More about Chiral Molecules For molecule with more than one chiral center: N chiral centers has 2n possible stereoisomers and 2 n-1 enantiomeric pairs. Diastereisomer: The optical isomers are not mirror image of each other. The diastereomers are physically and chemically distinguishable from one another. A solution contained equal amount of d and l isomer is known as racemic. It is optical inactive. Chiral molecules but no optical activity? A molecule which has an internal mirror symmetry plane, is known as meso compound. Even though meso compound has either one or more chiral centers, the molecule does not have enantiometic isomer.

10 Absolute Configuration Dilemma: Given a optical isomer, one can not tell whether it s in d or l form. : Cahn-Ingold-Prelog System optical isomer : The four groups attached to the chiral center are ranked according to their atomic number. SH > OH > NH2 > COOH > CHO > CH2OH > C6H5 > CH3 > 2 H > 1 H If the first atom in groups are the same, then the rank is based on the second atom in groups and so on. W > X > Y > Z Rotate the molecule so that the lowest priority group (Z) faces toward you. The order of the groups W X Y is clockwise, assigned R. The order of the groups W X Y is counter-clockwise, assigned S. Absolute Configuration W > X > Y > Z R, S configuration. The configuration of a molecule with multiple asymmetric centers can be described unambiguously.

11 Spectroscopic Properties All amino acids absorb in infrared region Only Phe, Tyr, and Trp absorb UV Absorbance at 280 nm is a good diagnostic device for amino acids NMR spectra are characteristic of each residue in a protein, and high resolution NMR measurements can be used to elucidate threedimensional structures of proteins UV spectrum

12 Superimposible return chemical formula ( ) Illustration of the chiral molecule return

13 optical isomers return