11

Amino Acids, Amino Acids,

22

Chapter OutlineChapter Outline Amino AcidsAmino Acids

– Amino acid classes (G1)Amino acid classes (G1)– Stereoisomers (G2)Stereoisomers (G2)– Bioactive AABioactive AA– Titration of AA (G3)Titration of AA (G3)– Modified AAModified AA– AA reactionsAA reactions

PeptidesPeptides ProteinsProteins

– Protein structureProtein structure– Fibrous proteinsFibrous proteins– Globular proteinsGlobular proteins

33

5.1 Amino Acid: Definition5.1 Amino Acid: Definition An alpha amino acid is a carboxylic acid An alpha amino acid is a carboxylic acid

with an amino group on the carbon alpha to with an amino group on the carbon alpha to the carboxylic acid .the carboxylic acid .

The alpha carbon also has an R group side The alpha carbon also has an R group side chain except for glycine which has two Hs.chain except for glycine which has two Hs.

Generic aminoacid at physiologicalpH: zwitterion form

C

CC

R

HNH3

+O

O

44

Definition, cont.Definition, cont. If the R group is not H, the AA can If the R group is not H, the AA can

exist in two exist in two enantiomericenantiomeric forms forms (nonsuperimposable mirror (nonsuperimposable mirror image) forms.)image) forms.)

C

C

R1

HNH3

+

OO

C

C

R1

H NH3

+

O O

Mirror plane carbon

55

Amino AcidsAmino AcidsGeneral form: General form:

1. an amino acid (AA); 1. an amino acid (AA); 2. two AA linked to form the peptide bond.2. two AA linked to form the peptide bond.

NC CR1

H

NH3

+O

C CR1

H

OOH

C

C

R1

HNH3

+

OO

PEPTIDE BONDL-form

66

Amino Acids-2Amino Acids-2 Only the L form of amino acids is Only the L form of amino acids is

commonly found in proteins.commonly found in proteins. Depending on the nature of the R Depending on the nature of the R

group, AA are classified into four group, AA are classified into four groups. groups. nonpolarnonpolarpolarpolaracidicacidicbasicbasic

77

AA with nonpolar side chains-1AA with nonpolar side chains-1

C

C

CH3

HNH3

+OO

alanine, Ala

CH2

C

C

HNH3

+OO

phenylalanine, Phe

C

C

CH2

HNH3

+OO

CHCH3

CH3

leucine,Leu

C

C

CH

HNH3

+OO

CH2CH3

CH3

isoleucine, I le

88

AA with nonpolar side chains-2AA with nonpolar side chains-2

C

C

CHHNH3

+OO

CH3 CH3CH2

C

C

HNH3

+OO

CH2S CH3

C

C

CH2

HNH2

+OO

CH2

CH2

valine, Val methionine, Met

proline, Pro

C

C

CH2

HNH3

+OO

CCH

NH

tryptophan, Trp

99

Contain hydrocarbon R groups.Contain hydrocarbon R groups. Hydrocarbons side chain can be Hydrocarbons side chain can be

aromatic or aliphatic.aromatic or aliphatic. Interact poorly with water.Interact poorly with water. Also refer as hydrophobic amino Also refer as hydrophobic amino

acids.acids.

AA with nonpolar side AA with nonpolar side chains-2chains-2

1010

AA with polar side chains-1AA with polar side chains-1

C

C

H

HNH3

+OO

CH2

C

C

HNH3

+OO

OH

C

C

CH2

HNH3

+OO

SH

Glycine, Gly Serine, Ser

cysteine, Cys

C

C

CHHNH3

+OO

CH3

OH

threonine, Thr

1111

AA with polar side chains-2AA with polar side chains-2

glutamine, Gln

tyrosine, Tyr

C NH2O

C

C

HNH3

+OO

CH2

C NH2O

CH2

C

C

HNH3

+OO

CH2

asparagine, Asn

OHC

C

CH2

HNH3

+OO

1212

AA with polar side chains-2AA with polar side chains-2

Have functional groups that easily Have functional groups that easily interact with water.interact with water.

Functional groups also capable in Functional groups also capable in forming hydrogen bonding.forming hydrogen bonding.

1313

AA: acidic and basicAA: acidic and basic

glutamic acid, GluC OO

C

C

HNH3

+OO

CH2

C OO

CH2

C

C

HNH3

+OO

CH2

aspartic acid, Asp

CH2

NH

CH2

CH2

CNH2

+NH2

C

C

HNH3

+OO

CH2

CH2

CH2

C

C

HNH3

+OO

CH2

NH3

+

NHCH

CH2

C

C

HNH3

+OO

C

NH+

CH

histidine, Hislysine, Lysarginine, Arg

1414

Acidic AA attached to carboxylate Acidic AA attached to carboxylate groups that is negatively charged at groups that is negatively charged at physiologically pH.physiologically pH.

Basic AA bear a positive charge at Basic AA bear a positive charge at physiological pH.physiological pH.

Basic AA can form ionic bonds with Basic AA can form ionic bonds with asidic AA.asidic AA.

1515

Amino Acid TitrationAmino Acid Titration At physiological pH, the carboxyl group At physiological pH, the carboxyl group

of the AA is negatively charged and the of the AA is negatively charged and the amino group is positively charged.amino group is positively charged.

Amino acids without charged side Amino acids without charged side chains are chains are zwitterionszwitterions and have and have no net no net chargecharge. H. H33

++N-CHR-COON-CHR-COO--.. A titration curve shows how the amine A titration curve shows how the amine

and carboxyl groups react with and carboxyl groups react with hydrogen ion.hydrogen ion.

1616

Amino Acid Titration-2Amino Acid Titration-2

At low pH a At low pH a nonacidic/nonbasic amino acid nonacidic/nonbasic amino acid is protonated and has the is protonated and has the structure below.structure below.

HH33NN++CHRCOOHCHRCOOHThe charge behavior of acidic The charge behavior of acidic

and basic AAs is more and basic AAs is more complex.complex.

1717

Titration of AlanineTitration of Alanine

1

mole base added1 2

pH

5

10

1

NH3

+CHR1

CO

OH

NH3

+CHR1

CO

O

NH3

+CHR1

CO

O

A

B

C

A A=BpK1=2.3

B, pI=pH=6.0

B=CpK2=9.73

C

1818

Isoelectric pointIsoelectric point The isoelectric point (pI) for an AA The isoelectric point (pI) for an AA

occurs when there is no net charge.occurs when there is no net charge. For a neutral AA, the pI is calculated For a neutral AA, the pI is calculated

using the equation pKusing the equation pK11 + pK + pK22/2/2 Eg.: alanine: 2.34 + 9.7 / 2 = 6.0Eg.: alanine: 2.34 + 9.7 / 2 = 6.0 For acidic or basic AAs, the pI is the For acidic or basic AAs, the pI is the

average of the two pKaverage of the two pKaa values values bracketing the isoelectric structure.bracketing the isoelectric structure.

1919

Isoelectric point-2Isoelectric point-2

In general the In general the pI is the pI is the average of the average of the two pKtwo pKaa’s ’s

bracketing the bracketing the isoelectric isoelectric structure. Eg.: structure. Eg.: glutamic acid, glutamic acid, pI = 3.2pI = 3.2

pK1=2.2

pK2=4.3

pK3=9.9

2020

5.2 Peptides5.2 Peptides Peptide: a polymer of about 2-100 AAs linked Peptide: a polymer of about 2-100 AAs linked

by the peptide(amide) bond. As the amino by the peptide(amide) bond. As the amino group and the carboxyl group link, water is group and the carboxyl group link, water is lost.lost.

C C

R1

H

NH3

+O

O

Peptide bonds

C C

R1

H

NH3

+O

OC C

R1

H

NH3

+O

O

C C

R1

H

NH3

+O

C C

R1

H

NH

OC C

R1

H

NH

OO

-H2O -H2O

2121

Peptides-2Peptides-2 A peptide is written with the N-terminal A peptide is written with the N-terminal

end to the left and the C-terminal end to end to the left and the C-terminal end to the right.the right.

HH22N-Tyr-Ala-Cys-Gly-COOHN-Tyr-Ala-Cys-Gly-COOH Name = TyrosylalanylcysteinylglycineName = Tyrosylalanylcysteinylglycine The peptide bond is rigid and planar due to The peptide bond is rigid and planar due to

the resonance contribution shown right.the resonance contribution shown right.

CC

O

NH

C

CC

O

NH

C

+

-

2222

Peptides-3Peptides-3

The peptide bond The peptide bond angles force angles force specific specific conformations of conformations of proteins and, on proteins and, on extended chains, extended chains, successive R successive R groups are on groups are on opposite sides.opposite sides.

2323

Physiologically Interesting PeptidesPhysiologically Interesting Peptides

CH

N

C

C

NH

CH2

NH3

+CH2CH2C

O

NH CH COO-

-alanyl-L-histidine

carbon

Common name: carnosinefound in muscle tissue

2424

Physiologically Interesting PeptidesPhysiologically Interesting Peptides

SHCH2

CH CH2CH2C

O

NH CH C

OCOO-

NH3

+NH CH2COO

-

-glutamyl-L-cysteineylglycine

Glutathione: the reduced formreduces oxidizing agents by dimerizing toform the disulfide bond with release of 2 H.

2525

Physiologically Interesting PeptidesPhysiologically Interesting Peptides

Tyr-Gly-Gly-Phe-LeuN-terminal AA C-terminal AA

Short form description for a peptide.Leucine enkephalin: a naturalanalgesic found in the brain

2626

Physiologically Interesting PeptidesPhysiologically Interesting Peptides

OxytocinInduces labor and aids in forcing milkfrom the mammaryglands.

Vassopressin has a Phe at position 3 instead of Ile and an Arg at position 8instead of a Leu. Its role is in regulatingblood pressure.

3

8

H3N+-Cys-Tyr-Ile

-Cys-Asn

|Gln |

|S |S

|Pro-Leu-Gly-NH2

2727

THE ENDTHE END