AMINO ACID AND PROTEIN CHEMISTRY

Maria Milagros Untalan-Magat, MD,MEM, FPPS,FPAPP

OBJECTIVES:OBJECTIVES:

•General functions of proteinsGeneral functions of proteins

•Structural composition of amino acidsStructural composition of amino acids

•Chemical propertiesChemical properties

•Hierarchy of protein organizationHierarchy of protein organization

Protein Structure and Function

Objective:Objective:

Lifelong learners

Independent learners

READ YOUR BOOKS!

• Polymers of amino acidsPolymers of amino acids– 20 amino acids20 amino acids– ““Alphabet” of protein Alphabet” of protein

structurestructure– Basic structural unitsBasic structural units

““Proteios”Proteios”

Proteins

Diversity in functionsDiversity in functions– Enzymatic catalysisEnzymatic catalysis– Transport and storageTransport and storage– Coordinated motion and Coordinated motion and

mechanical supportmechanical support– Immune protectionImmune protection– Generation and transmission Generation and transmission

of nerve impulsesof nerve impulses– Control of growthControl of growth

Proteins

Amino Acids: Amino Acids: StructureStructure

CNH3+ H

COO-

R

C NH3+H

COO-

R

L - configuration D - configuration

Amino Acids: Amino Acids: PropertiesProperties

• Tetrahedral carbonTetrahedral carbon– Asymmetric centerAsymmetric center– Chiral centerChiral center– StereocenterStereocenter

CNH3+ H

COO-

R • Side ChainSide Chain– FunctionFunction– ConformationConformation– Electrical Electrical

chargecharge

Amino Acids: Amino Acids: Functional Functional GroupsGroups

• ACIDICACIDIC

CNH3+ H

COO-

R

• CarboxylCarboxyl

• BASICBASIC• AmineAmine

• ImidazoleImidazole

• GuanidinoGuanidino

• NEUTRAL• AmidesAmides

• HydroxylHydroxyl

NH2COOHOH

• ACIDICACIDIC

CNH3+ H

COO-

R

• CarboxylCarboxyl

• BASICBASIC• AmineAmine

• ImidazoleImidazole

• GuanidinoGuanidino

• NEUTRAL• AmidesAmides

• HydroxylHydroxyl

Amino Acids: Amino Acids: Functional Functional GroupsGroups

Amino Acids: Functional GroupsGroup Characteristic Amino Acids

Negatively charged

Additional carboxyl group

Glutamic acid and Aspartic acid

Positively charged

Guanidino groupImmidazolee - B Group

ArginineHistidineLysine

Polar uncharged

OH containingAmide groupThiol group

Serine and threonineAsparagine and glutamineCysteine

Nonpolar aliphatic

No side chainImino groupHydrophobic alkyl groupThioether sulfur atom

GlycineProlineAlanine, valine, leucine, isoleucineMethionine

Aromatic Bulky aromatic side chains

Phenylalanine, tyrosine, tryptophan

Amino Acids: Classification

Amino Acids: Classification

Amino Acids: Classification

Amino Acids: Classification

Amino Acids: Classification

TitrationTitration Quantitative measure of Quantitative measure of

pKapKa Electric chargeElectric charge Buffering capacityBuffering capacity

CH3N+ R

COO

H

pH = 2pH = 7pH = 11NaOH

ZwitterionZwitterion Dipolar ionsDipolar ions

H

H2OH2N

Amino Acids: Ionic State

CNH3+ R

COOH

H

CNH3+ R

COO-

H

CNH2 R

COO-

H

pH = 2 pH = 7 pH = 11

H+

Zwitterion Dipolar ions

NaOH

H+

NaOH

Electric charge = +1

Electric charge = 0

Electric charge = -1

pI = pK1 + pK2

2

Amino Acids: Ionic State

0.5 1.0 1.5

1

2

3

4

5

6

7

8

9

10

11

12

Equivalents OH-

pH

pK2 = 9.7

pK1 = 2.3

pI = 6.0pK1

+ pK22

Titration Curve: Alanine

CNH3+

RCOOH

COOH

H

pK = 2.2

pK = 4.3

pK = 9.9

H20

NaOH

+1

0

-2

CNH3+

RCOOH

COO-

H

CNH3+

RCOO-

COO-

HCNH2

RCOO-

COO-

H

-1

NaOH

H20

H20

NaOH

Titration : Glutamic acid

CNH3+ R

COOH

H

CNH3+ R

COO-

H

CNH2 R

COO-

H

pH = 2 pH = 7 pH = 11

H+

Zwitterion Dipolar ions

NaOH

H+

NaOH

Electric charge = +1

Electric charge = 0

Electric charge = -1

pI = pK1 + pK2

2

Titration : Glutamic acid

0.5 1.0 1.5

1

2

3

4

5

6

7

8

9

10

11

12

Equivalents OH-

pH

pK2 = 9.9

pK1 = 2.2

pI = 3.25pK1

+ pKR2

pKR = 4.3

Titration curve: Glutamic acid

AMINO ACID pK1 pK2 pKR

ALANINE 2.35 9.87ARGININE 1.82 8.99 12.48

ASPARAGINE 2.1 8.84ASPARTIC ACID 1.99 9.90 3.90

CYSTEINE 1.92 10.78 8.33GLUTAMIC ACID 2.10 9.47 4.07

GLUTAMINE 2.17 9.13GLYCINE 2.35 9.78

HISTIDINE 1.80 9.33 6.04ISOLEUCINE 2.32 9.76

LEUCINE 2.33 9.74LYSINE 2.16 9.18 10.79

METHIONINE 2.13 9.28PHENYLALANINE 2.16 9.18

PROLINE 1.95 10.65SERINE 2.19 9.21 ~13

THREONINE 2.09 9.10 ~13TRYPTOPHAN 2.43 9.44

TYROSINE 2.20 9.11 10.13VALINE 2.29 9.74

Proteins:

Structural Organization

+OH HH2CH2N

H

C

R1 O

CN

H

COOH

R2

CH2N

H

C

O

CN

H

COOH

H

R1 R2

H2O+

Peptide bond formation

Covalent bond : – amino and – carboxyl groups Elimination of H2O

Partial double bond character - C, H, N, and O are co-planar Trans form is favored

Peptides: Characteristics

DNA - dependent Sequence of peptide-bonded amino acids Directionality – NH3 and COOH

Disulfide bonds

PRIMARY STRUCTURE

CH2N

H

C

OR1

CN

H

COO

H

R2

CN

H

COO

H

R3

CN

H

COOH

H

R4

Peptides: Structural Organization

Arrangement in space Motifs of hydrogen bonding

SECONDARY STRUCTURE

CH2N

H

C

OR1

CN

H

COO

H

R2

CN

H

COO

H

R3

CN

H

COO-

H

R4

Peptides: Structural Organization

Alpha helixAlpha helix

2o Sequence Beta PleatsBeta Pleats

Hydrogen bonds

Peptides: Structural Organization

3 – dimensional arrangement of atoms3 – dimensional arrangement of atoms Over-all folding of polypeptide chainOver-all folding of polypeptide chain Highest order for monomeric proteinHighest order for monomeric protein

TERTIARY STRUCTURE

Peptides: Structural Organization

Manner of interaction between subunits of multimeric proteins

Domains

QUATERNARY STRUCTURE

Types Assembly of two proteins that have two different

structures Multiple copies of the same protein

Peptides: Structural Organization

Heirarchy of Protein Structure

•Amino acids are built around an asymmetric - carbon.

•Amino acids are grouped based on similarities of side chain characteristics.•The primary structure of proteins is dictated by genetic information.

Thank you!

Please get 1 pc of yellow paper

1.1. Differentiate proteins, peptides & Differentiate proteins, peptides & amino acidsamino acids

2. Explain D, L system of configuration2. Explain D, L system of configuration

3. Define stereoisomerism; enantiomers3. Define stereoisomerism; enantiomers4. Define chirality4. Define chirality

5. Define polarity5. Define polarity

6. Describe zwitter ion6. Describe zwitter ion

7. Define R group : relevance7. Define R group : relevance8. Define pKa, pH, pI8. Define pKa, pH, pI