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

� 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

The Synthesis and Breakdown of Polymers

Animation: PolymersAnimation: Polymers

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

Fig. 5-2a

Dehydration removes a watermolecule, forming a new bond

Short polymer Unlinked monomer

Longer polymer

Dehydration reaction in the synthesis of a polymer

HO

HO

HO

H2O

H

HH

4321

1 2 3

(a)

Fig. 5-2b

Hydrolysis adds a watermolecule, breaking a bond

Hydrolysis of a polymer

HO

HO HO

H2O

H

H

H321

1 2 3 4

(b)

Proteins

Polysaccharides

Nucleic acids

� 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, peptides and proteins

Amino acids and theprimary 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 Are specific for what they will catalyzethey will catalyze

�� Are ReusableAre Reusable�� End in End in ––asease

--SucraseSucrase--LactaseLactase--MaltaseMaltase

Animation: EAnimation: Enzymesnzymes

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

ZwitterionicZwitterionic form of amino acidsform of amino acidsUnder normal cellular conditions amino

acids are zwitterions (dipolar ions):

Amino group = -NH3+

Carboxyl group = -COO-

Stereochemistry of amino acidsStereochemistry of amino acids�19 of the 20 common amino acids have a

chiral �-carbon atom (Glycine does not)

Stereochemistry of amino acidsStereochemistry of amino acids�Threonine and isoleucine have 2 chiral

carbons each (4 possible stereoisomers each)

Stereochemistry of amino acidsStereochemistry 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 non-

superimposable mirror images� The two mirror images are called enantiomers� Chiral molecules can rotate the plane of polarized

light

Animation: Animation: IsomersIsomers

� 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 L-form

Amino Acids: #21 (2001)

SelenocysteineSelenocysteine

Amino Acids: #22 (2002)

Pyrrolysine (4 R, 5 R)

N

NH2

CO2H

NHCO

X

CH3

NH2

OH

X=

Four aliphatic amino acid structuresFour aliphatic amino acid structures

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

ProlineProline has a nitrogen in the has a nitrogen in the aliphatic ring systemaliphatic ring system

�Proline (Pro, P) - has a three carbon side chain bonded to the �-amino nitrogen

�The heterocyclic pyrrolidinering restricts the geometryof 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 Structures of histidinehistidine, lysine and , lysine and argininearginine

His: Catalytically, most important type of residue

H+

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.

Free-energy change for transfer (kjmol-1)

Aminoacid

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 andtyrosine

� Epinephrine is a "fight or flight" hormone, and plays a central role in the short-term stressreaction. It is released from the adrenal glands when danger threatens or in an emergency

Titration curve for Titration curve for alaninealanine

Titration curves are used to determine pKavalues

� pK1 = 2.4

� pK2 = 9.9

� pIAla = isoelectricpoint

Ionization of Ionization of HistidineHistidine

Titration curve of histidine

� pK1 = 1.8

� pK2 = 6.0

� pK3 = 9.3

DeprotonationDeprotonation of of imidazoliumimidazolium ringring

Amino Acids with Neutral Side Chains

CC CC

OO

OO––

HH

HH

HH33NN++

GlycineGlycineppKKa1a1 = = 2.342.34ppKKa2a2 == 9.609.60ppI I == 5.975.97

AlanineAlanineppKKa1a1 = = 2.342.34ppKKa2a2 == 9.699.69ppI I == 6.006.00

HH33NN CC CC

OO

OO––

CHCH33

HH++

Amino Acids with Neutral Side Chains

ProlineProlineppKKa1a1 = = 1.991.99ppKKa2a2 == 10.6010.60ppI I == 6.306.30

HH22NN CC CC

OO

OO––HH

++

CHCH22HH22CCCCHH22

Amino Acids with Neutral Side Chains

Amino Acids with IonizableSide Chains

Aspartic acidAspartic acidppKKa1a1 = = 1.881.88ppKKa2a2 == 3.653.65ppKKa3a3 == 9.60 9.60 ppI I == 2.772.77

HH33NN CC CC

OO

OO––HH

++

OOCCCHCH22

OO

––

�� For amino acids with acidic side chains, For amino acids with acidic side chains, pI is the average of ppI is the average of pKKa1a1 and pand pKKa2a2

TyrosineTyrosineppKKa1a1 = = 2.202.20ppKKa2a2 == 9.119.11ppKKa3a3 == 10.07 10.07 ppI I == 5.665.66

HH33NN CC CC

OO

OO––HH

++

CHCH22

OHOH

Amino Acids with IonizableSide Chains

CysteineCysteine HH33NN CC CC

OO

OO––

CHCH22SSHH

HH++ ppKKa1a1 = = 1.961.96

ppKKa2a2 == 8.188.18ppKKa3a3 == 10.28 10.28 ppI I == 5.075.07

Amino Acids with IonizableSide Chains

LysineLysine

ppKKa1a1 = = 2.182.18ppKKa2a2 == 8.958.95ppKKa3a3 == 10.5310.53ppI I == 9.749.74

HH33NN CC CC

OO

OO––HH

++

CHCH22CHCH22CHCH22CHCH22NNHH33

++

�� For amino acids with basic side chains, For amino acids with basic side chains, pI is the average of ppI is the average of pKKa2a2 and pand pKKa3a3

Amino Acids with IonizableSide Chains

Peptide Bonds Link Amino Acids Peptide Bonds Link Amino Acids in Proteinsin 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 betweenPeptide bond betweentwo amino acidstwo 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 (aspartylphenylalaninemethyl ester)

�About 200 times sweeter than table sugar

�Used in diet drinks

Amino Acid Composition of ProteinsAmino 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 Planar peptide groups in a polypeptide chainpolypeptide 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