chapter 18 amino acids, proteins and enzymes. amino acids 20 amino acids; all are α-amino acids:

Chapter 18 Amino Acids,Proteins

and Enzymes

Amino Acids

• 20 amino acids; all are α-amino acids:

20 Amino Acids

• Essential AA’s– Isoleucine– Leucine– Lysine– Methionine– Phenylalanine– Threonine– Tryptophan– Valine– Arginine– Histidine

• Non-Essential AA’s– Alanine– Asparagine– Aspartate– Cysteine– Glutamate– Glutamine– Glycine– Proline– Serine– Tyrosine

• Non-protein significance of AA’s– Tryptophan precursor for serotonin, melatonin and

niacin

Tryptophan

Serotonin

Melatonin

Niacin

– Glycine is a precursor for porphyrins such as heme

GlycinePorphyrin

Heme B

‘Non-Protein’ Amino Acids

• β-Alanine– Carnosine

• β-alanyl-L-histidine

– Anserine• β-alanyl-N1-methyl-L-histidine

– Glutathione• γ-L-glutamyl-L-cysteinylglycine

Classification of AA R groups(Pg. 549)

• Nonpolar Side Chains– Proline: a secondary amine – Methionine: contains S– Tryptophan & Phenylalanine: aromatic rings

• Polar, Neutral Side Chains– Cysteine: S-H group– Tyrosine: aromatic ring

• Acidic Side Chains• Basic Side Chains

Zwitterions

R-CH-COH

NH2

OR-CH-CO-

NH3+

O

Un-ionizedform

Zwitterion

Although -amino acids are commonly written in the un-ionized form, they are more properly written in the zwitterion (internal salt) form.

- Unionized form doesn’t exist in aqueous soln. or solid state

- All have high melting pts

- All are soluble in water

COOH donates H to NH2

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Isoelectric PointIsoelectric Point• Isoelectric Isoelectric

point, pI:point, pI:

the pH at which the majority of molecules of a compound in solution have no net charge

6.025.41

5.655.976.026.025.745.486.305.686.53

5.895.97

pI

valinetryptophan

threonineserineprolinephenylalaninemethionineleucineisoleucineglycineglutamine

asparaginealanine

Nonpolar &polar side chains

10.76

2.98

5.023.08

7.649.74

5.63

pI

tyrosine

lysinehistidine

glutamic acidcysteine

aspartic acid

arginine

AcidicSide Chains

BasicSide Chains pI

H NH3+

COO-

CH3

+H3N H

COO-

CH3

H OH

CHO

CH2OH

HO H

CHO

CH2OH

D-Alanine L-Alanine

D-Glyceraldehyde L-Glyceraldehyde

the naturally occurring form

the naturally occurring form

Handedness or Chirality

All but one of the AA’s are of the L configuration, which means that their configuration around the central Carbon is similar to that of L-glyceraldehyde.

“Left Handed”

Stereocenter

Enantiomers

• Enantiomers (optical isomers): the 2 mirror image forms of a chiral molecule– Same formula but different arrangement

• ALL enantiomers are stereoisomers– Same formula, same chemical groups

(COOH, NH3, etc.) but different spatial arrangement (like cis-trans)

• Enantiomeric pairs differ in effect on polarized light.

Blue represents which atom? Red? White? Grey?

Which AA is this?

(Note: this is not the zwitterionic form)

Peptides and Polypeptides

• Peptide bond - Review• Naming Conventions

– Amino end (N-terminal)Carboxyl end (C-Terminal)

– ‘yl’ added to name except to C-Terminal AA– Ser-gly-ala not the same as Ala-gly-ser

• Primary Structure = AA sequence

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Primary StructurePrimary Structure• Primary structure:Primary structure: the sequence of amino acids in

a polypeptide chain• The number peptides derived from the 20 protein-

derived amino acids is enormous• there are 20 x 20 = 400 dipeptides possible• there are 20 x 20 x 20 = 8000 tripeptides possible• the number of peptides possible for a chain of nn amino

acids is 2020nn

• for a small protein of 60 amino acids, the number of proteins possible is 2060 = 1078, which is possibly greater than the number of atoms in the universe!

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Primary StructurePrimary Structure• Just how important is the exact amino acid

sequence?• human insulin consists of two polypeptide chains

having a total of 51 amino acids; the two chains are connected by disulfide bonds

• in the table are differences between four types of insulin

A Chainpositions 8-9-10

B Chainposition 30

HumanCow

Hog

Sheep

-Thr-Ser-Ile--Ala-Ser-Val-

-Thr-Ser-Ile-

-Ala-Gly-Val-

-Thr-Ala

-Ala

-Ala

1o Structure Crucial to Function

• Hemoglobin and Sickle Cell Anemia– Normal Hb: -Thr-Pro-Glu-Glu-Lys-Ala Position: 4 5 6 7 8 9

– Sickle Cell: -Thr-Pro-Val-Glu-Lys-Ala

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Primary StructurePrimary Structure• vasopressin and oxytocin are both nonapeptides but

have quite different biological functions• vasopressin is an antidiuretic hormone• oxytocin affects contractions of the uterus in childbirth

and the muscles of the breast that aid in the secretion of milk

Cys S S Cys Pro Gly NH2

Tyr AsnPhe Gln

Cys S S Cys Pro Leu NH2

Tyr AsnIle Gln

Vasopressin Oxytocin

Primary Structure

• The ‘linear’ AA sequence

• Protein ‘Backbone’ consists of the alpha C, amino N and Carboxyl C. The 6 atoms, from alpha-C to alpha-C are arranged within an imaginary plane. – Important in 2o structure

Shape-Determining Interactions in Proteins

• H-bonding along backbone

• R-group interactions– H-bonding – Hydrophobic interactions– Salt bridges– Covalent bonds

• S-S

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Secondary StructureSecondary Structure• Secondary structure:Secondary structure: conformations of amino

acids in localized regions of a polypeptide chain• the most common types of secondary structure are -

helix and -pleated sheet• -helix:-helix: a type of secondary structure in which a

section of polypeptide chain coils into a spiral, most commonly a right-handed spiral

• -pleated sheet:-pleated sheet: a type of secondary structure in which two polypeptide chains or sections of the same polypeptide chain align parallel to each other; the chains may be parallel or antiparallel

Interaction: H-bonding along backbone

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-Helix-Helix

Hydrogen bonds are between the C=O of peptide bond and the H-N of another peptide linkage 4 AA’s further along the chain.

Grey = C

Blue = N

Red = O

Yellow = R-group

White = H

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-Pleated Sheet-Pleated Sheet

Grey = C

Blue = N

Red = O

Yellow = R-group

White = H

Beta-pleated sheet can be parallel or anti-parallel

Fibrous Proteins• Fibrous Proteins (water-insoluble)

– Water Insoluble– Secondary Structure determines nature

• Ex. Alpha-keratins– Hair, fingernails, wool

– Composition of alpha-helixes; multiple strands twist together

• Ex. Fibroin– Silk

– Composed of b-sheets

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Collagen Triple HelixCollagen Triple Helix

Tertiary Structure

• Overall Conformation of a Peptide chain

– How it folds, interactions between various AA’s along the chain.

• Determined by interactions of R-groups– Hydrophobic– Salt-bridges– H-bonds– disulfide

Example of a Globular Protein

• Myoglobin– Conjugated Globular Protein

• Contains a heme group

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Quaternary StructureQuaternary Structure• Quaternary structure:Quaternary structure: the arrangement of

polypeptide chains into a noncovalently bonded aggregation• the individual chains are held in together by hydrogen

bonds, salt bridges, and hydrophobic interactions

• Hemoglobin• adult hemoglobin:adult hemoglobin: two alpha chains of 141 amino acids

each, and two beta chains of 146 amino acids each• each chain surrounds an iron-containing heme unit• fetal hemoglobin:fetal hemoglobin: two alpha chains and two gamma

chains; fetal hemoglobin has a greater affinity for oxygen than does adult hemoglobin

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HemoglobinHemoglobin

Chemical Properties of Proteins

• Hydrolysis – breaking of peptide bonds– By enzymes– By acid

• Denaturation – disruption of non-covalent bonds– Heat– Mechanical agitation– Detergents– pH change

• Disrupt salt-bridges

– Solvents• Disrupt hydrophobic interactions