Download Amino Acids, Proteins and Enzymes

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
Serotonin
Melatonin
Tryptophan
Niacin
– Glycine is a precursor for porphyrins such as heme
Glycine
Porphyrin
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
Although -amino acids are commonly written in the unionized form, they are more properly written in the zwitterion
(internal salt) form.
O
R-CH-COH
O
R-CH-CO-
NH2
Un-ionized
form
NH3 +
Zwitterion
COOH donates
H to NH2
- Unionized form doesn’t exist in aqueous soln. or solid state
- All have high melting pts
- All are soluble in water
21Isoelectric Point
• Isoelectric
point, pI:
the pH at
which the
majority of
molecules of
a compound
in solution
have no net
charge
© 2003 Thomson Learning, Inc.
All rights reserved
N onpolar &
p olar side chains
alanine
asp aragine
cys teine
glutamin e
glycin e
is oleucine
leucin e
methionine
p henylalanine
p roline
serine
th reonine
tyrosine
tryptop han
valine
pI
6.02
5.41
5.02
5.65
5.97
6.02
6.02
5.74
5.48
6.30
5.68
6.53
5.63
5.89
5.97
Acid ic
Side Chain s
pI
aspartic acid 2.98
glutamic acid 3.08
Basic
Side Chains
arginine
histid ine
lysin e
pI
10.76
7.64
9.74
21-8
Handedness or Chirality
-
-
COO
H
NH3 +
COO
+
H3 N
CH3
D-A lanine
H
OH
CH2 OH
D -Glycerald ehyde
H
CH3
L-Alan ine
CHO
the n aturally
occu rring form
the n aturally
occu rring form
“Left
Handed”
CHO
HO
H
CH2 OH
Stereocenter
L-Glycerald ehyde
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 Lglyceraldehyde.
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 (CTerminal)
– ‘yl’ added to name except to C-Terminal AA
– Ser-gly-ala not the same as Ala-gly-ser
• Primary Structure = AA sequence
21Primary Structure
• Primary structure: the sequence of amino acids in
a polypeptide chain
• The number peptides derived from the 20 proteinderived 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 n amino
acids is 20n
• 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!
© 2003 Thomson Learning, Inc.
All rights reserved
21-13
21Primary 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
Human
Cow
Hog
Sh eep
© 2003 Thomson Learning, Inc.
All rights reserved
A Chain
p ositions 8-9-10
B Chain
p os ition 30
-Thr-Ser-Ile-A la-Ser-Val-Thr-Ser-Ile-Ala-Gly-Val-
-Thr
-Ala
-Ala
-Ala
21-14
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
21Primary 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
A sn
Ph e Gln
Vas op res sin
© 2003 Thomson Learning, Inc.
All rights reserved
Cys S S Cys Pro Leu NH2
Tyr
A sn
Ile
Gln
Oxytocin
21-16
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
21Secondary Structure
• Secondary structure: conformations of amino
acids in localized regions of a polypeptide chain
• the most common types of secondary structure are helix and b-pleated sheet
• -helix: a type of secondary structure in which a
section of polypeptide chain coils into a spiral, most
commonly a right-handed spiral
• b-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
© 2003 Thomson Learning, Inc.
All rights reserved
21-19
21-Helix
Grey = C
Blue = N
Red = O
Yellow = Rgroup
White = H
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.
© 2003 Thomson Learning, Inc.
All rights reserved
21-20
21b-Pleated Sheet
Grey = C
Blue = N
Red = O
Yellow = Rgroup
White = H
© 2003 Thomson Learning, Inc.
All rights reserved
21-21
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
21Collagen Triple Helix
© 2003 Thomson Learning, Inc.
All rights reserved
21-24
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
21Quaternary 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: 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: two alpha chains and two gamma
chains; fetal hemoglobin has a greater affinity for
oxygen than does adult hemoglobin
© 2003 Thomson Learning, Inc.
All rights reserved
21-28
21Hemoglobin
© 2003 Thomson Learning, Inc.
All rights reserved
21-29
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