Ch1: Amino Acids, Peptides, Proteins (copy)

Sickle Cell Disease

Glutamic acid to valine in RBC

Hemoglobin aggregate and precipitate

Amino Acids

Molecules with amino and carboxyl functional groups

a-Amino Acids

Amino, carboxyl, H, and R group bound to a-carbon

Side Chains

R group

Determine amino acid properties and functions

Proteinogenic Amino Acids

20 a-amino acids coded by human genome

Amino Acid Stereochemistry

All (not glycine) are chiral

All are L-amino acids (eukaryotes)

All (not cysteine) have S configuration

Amino Acid Weight

110 Daltons

Nonpolar Amino Acids

I Glided Low and Tripped Mr. Alan Phenyl Very Profanely

Isoleucine, glycine, leucine, tryptophan, methionine, alanine, phenylalanine, valine, proline

Aromatic Amino Acids

Tiger Tripped Pheonix

Tyrosine, tryptophan, phenylalanine

Polar Amino Acids

Sarah Thought Tyler Glued Asparagus to Cat

Serine, threonine, tyrosine, glutamine, asparagine, cysteine

Acidic/Negative Amino Acids

Aspartic acid (aspartate anion)

Glutamic acid (glutamate anion)

Mostly in deprotonated/anion form in the body

Basic/Positive Amino Acids

Lyzzie Argued Historically

Lysine, arginine, histidine

Isoleucine

I, Ile

Glycine

G, Gly

Smallest amino acid

Achiral

Leucine

L, Leu

Tryptophan

W, Trp

Double ring with N

Methionine

M, Met

S in side chain

Alanine

A, Ala

Phenylalanine

F, Phe

Benzyl (benzene + CH2)

Valine

V, Val

Proline

P, Pro

Cyclic

Reduce flexibility in secondary structure

Serine

S, Ser

OH in side chain

H bond

Threonine

T, Thr

OH in side chain

H bond

Tyrosine

Y, Tyr

Benzyl + OH

Glutamine

Q, Gln

Amide side chain

No charge change with pH change

Asparagine

N, Asn

Amide side chain

No charge change with pH change

Cysteine

C, Cys

Thiol (SH) group

Prone to oxidation

Aspartic Acid

D, Asp

Carboxylate side chain

Glutamic Acid

E, Glu

Carboxylate side chain

Lysine

K, Lys

Terminal primary amino group

Arginine

R, Arg

3 N (disperse charge)

Histidine

H, His

Aromatic ring with 2 N (imidazole)

Hydrophobic Amino Acids

Long akyl side chains

Inside protein

Hydrophilic Amino Acids

Charged side chains

Protein surface

isoleucine

glycine

leucine

tryptophan

methionine

alanine

phenylalanine

valine

proline

serine

threonine

tyrosine

glutamine

asparagine

cysteine

lysine (protonated)

arginine (protonated)

histidine (protontated)

aspartate (deprotonated)

glutamate (deprotonated)

Amphoteric Species

Accept or donate proton depending on pH

Ex: Amino acids

Ionizable Groups

Acidic (low pH): Gain protons/protonated

Basic (high pH): Lose protons/deprotonated

pKa

pH when half molecules are deprotonated (buffer)

[HA] = [A-]

Amino acids have at least 2

Flat titration curve

pH < pKa

More protonated

pH > pKa

More deprotonated

pKa1

pKa for carboxyl

~2

pKa2

pKa for amino

9-10

Positive Charge in Acidic Conditions

pH < pKa1 and pKa2

Carboxyl protonated (neutral)

Amino protonated (positive)

Amino and carboxyl groups fully protonated

Positive molecule

Zwitterions at Intermediate pH

pH > pKa1: Carboxyl deprotonated (negative)

pH < pKa2: Amino protonated (positive)

Neutral molecule

Negative Charge in Basic Conditions

pH > pKa1 and pKa2

Carboxyl deprotonated (negative)

Amino deprotonated (neutral)

Negative molecule

Isoelectric Point (pI)

pH when amino acid is electrically neutral

Average of 2 closest pKa values

Vertical titration curve

Acidic Side Chains

Low pI

Negative charge

Average of pKaR and pKa1

Basic Side Chains

High pI

Positive charge

Average of pKaR and pKa2

Peptides

Composed of amino acid residues joined by peptide bonds

Peptide Bond

Special amide bond between -COO- and NH3+

Form functional group -C(O)NH-

Dipeptide

2 amino acid residues

Tripeptide

3 amino acid residues

Oligopeptide

Small peptides (≤20)

Polypeptide

Long peptides

Peptide Bond Formation Reaction

Condensation/dehydration (release H2O)

Acyl substitution

Electrophilic carbonyl C attack nucleophilic amino group

Peptide Bond Resonance

Restrict rotation around C-N amide bond

N-Terminus

Free amino end

Left

C-Terminus

Free carboxy end

Right

Peptide Bond Hydrolysis

Trypsin and chymotrypsin cleave amide bond

Add H to amide N and OH to carbonyl C

Protein

Polypeptide with important biological functions (enzymes, hormones, membrane pores and receptors, cell structure)

Primary Protein Structure

Linear amino acid arrangement

N- to C- terminus

Primary Structure Stabilization

Covalent peptide bonds

Determining Primary Structure

Sequencing with DNA or protein

Secondary Protein Structure

Local structure determined by neighbouring amino acids

a-helices

b-pleated sheets

Secondary Structure Stabilization

H bonds

a-Helix

Clockwise-coiled peptide chain

H bonds every 4 residues

Side chains point away from core

Form keratin

b-Sheet

Parallel or antiparallel peptide chains

Side chains point above or below sheet plane

Form fibroin

Secondary Structure: Proline

Proline cause kinks

Found in a-helix start and b-sheet turns

Fibrous Protein

Sheets/strands

Collagen

Globular Proteins

Spherical

Myoglobin

Tertiary Protein Structure

3D protein shape

Tertiary Structure Stabilization

R group interactions

Electrostatic interactions

H bonds

Acid-base interactions form salt bridges

IMF

Tertiary Structure: Hydrophobic Residues

Protein interior

Pull in hydrophilic N-H and C=O bonds to form electrostatic interactions and H bonds

Tertiary Structure: Hydrophilic Residues

Protein surface

Tertiary Structure: Disulfide Bonds

Between cysteines to form cystine

Molten Globules

Intermediate states from secondary to tertiary structure

Solvation Layer

Solvent molecules lining solute in solution

Hydrophilic amino acids on exterior increase entropy and decrease Gibbs energy

Quaternary Protein Structure

1+ polypeptide chains (not present in all proteins)

Aggregation of globular subunits

Quaternary Structure: Stability

Decrease surface area = more stable

Quaternary Structure: DNA

Decrease DNA needed to code protein

Quaternary Structure: Catalytic Sites

Bring close together