Amino Acids

Chemical Constituents of Organisms: Part I Amino Acids

Overview: The Molecules of Life All living things are made up of four classes of large biological molecules: carbohydrates, lipids, proteins, and nucleic acids Within cells, small organic molecules are joined together to form larger molecules Macromolecules are large molecules composed of thousands of covalently connected atoms Molecular structure and function are inseparable Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Macromolecules are polymers, built from monomers • • •

A polymer is a long molecule consisting of many similar building blocks These small building-block molecules are called monomers Three of the four classes of life’s organic molecules are polymers: Carbohydrates Proteins Nucleic acids

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Synthesis and Breakdown of Polymers A condensation reaction or more specifically a dehydration reaction occurs when two monomers bond together through the loss of a water molecule Enzymes are macromolecules that speed up the dehydration process Polymers are disassembled to monomers by hydrolysis, a reaction that is essentially the reverse of the dehydration reaction Animation: Polymers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 5-2a

HO

1

2

3

H

Short polymer

HO

Unlinked monomer

Dehydration removes a water molecule, forming a new bond

HO

1

2

H

3

H2O

4

H

Longer polymer (a) Dehydration reaction in the synthesis of a polymer

Fig. 5-2b

HO

1

2

3

4

Hydrolysis adds a water molecule, breaking a bond

HO

1

2

3

(b) Hydrolysis of a polymer

H

H

H2O

HO

H

Proteins

Polysaccharides

Nucleic acids

Amino acids, peptides and proteins Proteins are polymers constructed from the same set of 20 amino acids Polymers of amino acids are called polypeptides A protein consists of one or more polypeptides, each folded into a specific 3D structure

Amino acids and the primary structure of proteins Important biological functions of proteins Enzymes, the biochemical catalysts Storage and transport of biochemical molecules Physical cell support and shape (tubulin, actin, collagen) Mechanical movement (flagella, mitosis, muscles)

Enzymes

What Are Enzymes? Most enzymes are Proteins (tertiary and quaternary structures) Act as Catalyst to accelerates a reaction Not permanently changed in the process

Enzymes Are specific for what they will catalyze Are Reusable End in –ase -Sucrase -Lactase -Maltase

Animation: Enzymes Enzymes

General structure of amino acids 20 common -amino acids have carboxyl and amino groups bonded to the -carbon atom A hydrogen atom and a side chain (R) are also attached to the -carbon atom

Zwitterionic form of amino acids Under normal cellular conditions amino acids are zwitterions (dipolar ions): Amino group = Carboxyl group =

-NH3+ -COO-

Stereochemistry of amino acids 19 of the 20 common amino acids have a chiral -carbon atom (Glycine does not)

Stereochemistry of amino acids Threonine and isoleucine have 2 chiral carbons each (4 possible stereoisomers each)

Stereochemistry of amino acids Proteins are assembled from L-amino acids (a few D-amino acids occur in nature) They are classified as , , , etc. amino acids according the carbon that bears the nitrogen

Amino acids Our bodies can synthesize about 10 amino acids Essential amino acids are the other 10 amino acids, which have to be ingested The α-carbon in all amino acids except glycine is chiral (has 4 different groups attached to it) Chiral molecules exist as two nonsuperimposable mirror images The two mirror images are called enantiomers Chiral molecules can rotate the plane of polarized light Animation: Isomers

The enantiomer that rotates the plane of polarized light to the left is called L- (laevus = “left”) and the other enantiomer is called D(dexter = right) Enantiomers have identical physical and chemical properties. They only differ in their interaction with other enantiomers Most amino acids in proteins exist in the Lform

Amino Acids: #21 (2001)

Selenocysteine

Amino Acids: #22 (2002) CO2 H H2 N

X= CH3 HN N

NH2

CO X

OH

Pyrrolysine (4 R, 5 R)

Four aliphatic amino acid structures

Gly: The smallest side chain associated with sharp turns and flexibility It is the only one in the table that is achiral

Proline has a nitrogen in the aliphatic ring system Proline (Pro, P) - has a three carbon side chain bonded to the -amino nitrogen The heterocyclic pyrrolidine ring restricts the geometry of polypeptides

Aromatic amino acid structures

Methionine and cysteine

Formation of cystine

Side Chains with Alcohol Groups Serine (Ser, S) and Threonine (Thr, T) have uncharged polar side chains

Structures of histidine, lysine and arginine

H+

His: Catalytically, most important type of residue

Structures of aspartate, glutamate, asparagine and glutamine

The hydrophobicity of amino acid side chains Hydropathy: the relative hydrophobicity of each amino acid The larger the hydropathy, the greater the tendency of an amino acid to prefer a hydrophobic environment Hydropathy affects protein folding: hydrophobic side chains tend to be in the interior while hydrophilic residues tend to be on the surface

Hydropathy scale for amino acid residues (Free-energy change for transfer of an amino acid from interior of a lipid bilayer to water) Usually interior of proteins away from water. Hydrocarbon: do not contain polar atoms.

Amino acid

Free-energy change for transfer (kjmol-1)

Compounds derived from common amino acids

Epinephrine Epinephrine (also referred to as adrenaline) is a hormone and neurotransmitter. It is a catecholamine, a sympathomimetic monoamine derived from the amino acids phenylalanine and tyrosine Epinephrine is a "fight or flight" hormone, and plays a central role in the short-term stress reaction. It is released from the adrenal glands when danger threatens or in an emergency

Titration curve for alanine Titration curves are used to determine pKa values pK1 = 2.4 pK2 = 9.9 pIAla = isoelectric point

Ionization of Histidine Titration curve of histidine pK1 = 1.8 pK2 = 6.0 pK3 = 9.3

Deprotonation of imidazolium ring

Amino Acids with Neutral Side Chains

Glycine

+ H3N

H C H

O C

– O

pKa1 = pKa2 = pI =

2.34 9.60 5.97

Amino Acids with Neutral Side Chains

Alanine

+ H3N

H C CH3

O C

– O

pKa1 = pKa2 = pI =

2.34 9.69 6.00

Amino Acids with Neutral Side Chains

Proline

+ H2N H2C

H C C H2

O C CH2

– O

pKa1 = pKa2 = pI =

1.99 10.60 6.30

Amino Acids with Ionizable Side Chains Aspartic acid

+ H3N

H C

– OCCH2

O C

– O

pKa1 = pKa2 = pKa3 = pI =

1.88 3.65 9.60 2.77

O

For amino acids with acidic side chains, pI is the average of pKa1 and pKa2

Amino Acids with Ionizable Side Chains Tyrosine

+ H3N

H C CH2

OH

O C

– O

pKa1 = pKa2 = pKa3 = pI =

2.20 9.11 10.07 5.66

Amino Acids with Ionizable Side Chains Cysteine

+ H3N

H C

O C

CH2SH

– O

pKa1 = pKa2 = pKa3 = pI =

1.96 8.18 10.28 5.07

Amino Acids with Ionizable Side Chains + H3N

H C

O C

– O

+ CH2CH2CH2CH2NH3

pKa1 = pKa2 = pKa3 = pI =

2.18 8.95 10.53 9.74

Lysine

For amino acids with basic side chains, pI is the average of pKa2 and pKa3

Peptide Bonds Link Amino Acids in Proteins Peptide bond - linkage between amino acids is a secondary amide bond Formed by condensation of the -carboxyl of one amino acid with the -amino of another amino acid (loss of H2O molecule) Primary structure - linear sequence of amino acids in a polypeptide or protein

Peptide bond between two amino acids

Polypeptide chain nomenclature Peptide chains are numbered from the N (amino) terminus to the C (carboxyl) terminus Example: (N) Gly-Arg-Phe-Ala-Lys (C) (or GRFAK) Formation of peptide bonds eliminates the ionizable -carboxyl and -amino groups of the free amino acids

Aspartame, an artificial sweetener Aspartame is a dipeptide methyl ester (aspartylphenylalanine methyl ester) About 200 times sweeter than table sugar Used in diet drinks

Amino Acid Composition of Proteins • Amino acid analysis - determination of the amino acid composition of a protein • Peptide bonds are cleaved by acid hydrolysis (6M HCl, 110o, 16-72 hours) • Amino acids are separated chromatographically and quantitated • LC-MS-MS peptide sequencing

Acid-catalyzed hydrolysis of a peptide

Resonance structure of the peptide bond (a) Peptide bond shown as a C-N single bond (b) Peptide bond shown as a double bond (c) Actual structure is a hybrid of the two resonance forms. Electrons are delocalized over three atoms: O, C, N

Planar peptide groups in a polypeptide chain Rotation around C-N bond is restricted due to the double-bond nature of the resonance hybrid form Peptide groups (blue planes) are therefore planar

Next lesson: Peptides and Protein