Introduction to Organic and
Biochemistry
(CHE 124)
Reading Assignment
General, Organic, and Biological Chemistry: An Integrated Approach
3rd. Ed. Ramond
Chapter 12
Peptides, Proteins, and Enzymes
Protein
• Linear, unbranched polymer of 50 or more
amino acids. Amino acids are connected
through peptide bonds (amide linkage).
• The linear sequence of amino acids folds into
a three dimensional structure.
Functions of Proteins
• Enzymatic catalysis most chemical reactions in the cell are
carried out by enzymes ,which are globular proteins. They
increase the rate of chemical reactions by reducing the
energy of activation.
• Transport and storage small molecules are moved throughout
the cell by specific transporters. ie hemoglobin transports O2
in the blood.
• Mechanical support the high tensile strength of bone and skin
is due to the presence of collagen, a fibrous protein.
• Coordinate motion muscles are made mostly of proteins.
Contraction of muscles relies on the sliding motion of two
types of proteins, actin and myosin. Motion of a flagella and
movement of chromosomes in mitosis also relies on proteins.
Functions of Proteins
• Generate and transmission of nerve impulses sending and
receiving messages between nerve cells requires receptor
proteins that detects the presence of acetylcholine.
• Control of growth and differentiation proteins turn the
expression of other proteins on and off by binding to specific
sequences on DNA.
• Immune protection antibodies are highly specific proteins that
identify and remove foreign substances from the cell.
Definitions
• Glucogenic Amino Acids
– Carbon skeleton is converted into intermediate(s) that
can be used to synthesize glucose.
• Ketogenic Amino Acids
– Carbon skeleton is converted into intermediate(s) (acetyl
CoA or Acetoacetyl CoA) that can form ketone bodies or
fatty acids
– NOT substrate for glyconeogenesis
• Nonessential Amino Acids
– enzymes present for de novo synthesis of these amino
acids
• Essential Amino Acids – (TV FILM HWK)
– Organism lacks enzymes to synthesize the amino acids.
Amino Acid Backbone
• 20 naturally occurring
amino acids are
incorporated into
proteins.
• Living systems contain
– L amino acids
Amino Acids
• GLUCOGENIC
BOTH
NONESSENTIAL
– Alanine (A, Ala)
– Arginine (R, Arg)*
– Asparagine (N,Asn )
– Aspartate (D, Asp)
– Cysteine (C, Cys)
– Glutamate (E, Glu)
– Glutamine (Q, Gln)
– Glycine (G, Gly)
– Proline (P, Pro)
– Serine (S, Ser)
NONESSENTIAL
– Tyrosine (Y, Tyr)
ESSENTIAL
ESSENTIAL
(Val and His Three Methods)
–
–
–
–
Histidine (H, His)*
Methionine (M, Met)
Threonin (T, Thr)
Valine (V, Val)
Essential: TV FILM HWK
(Iley Trpped BOTH Phesants)
Lysine
– Isoleucine (I, ile)
– Phenylalanine (F, Phe)
– Tryptophane (W, Trp)
KETOGENIC
NONESSENTAIL
ESSENTAIL
KETONES in Leu of
--Leucine (L, Leu)
-- Lysine (K, Lys)
Updated 2014
Cyclic (1)
Name
Proline
Structure
M.W.
One
Three
Type
R group
pKa
75
P
Pro
Nonpolar
----
• Proline is associated with bends, kinks or tight turns in protein
structure.
• Often followed by glycine in hairpin turns.
Aliphatic (5)
Name
Structure
MW One
Glycine
Three
Type
R
group
pKa
75
G
Gly
Nonpolar
----
Alanine
89
A
Ala
Nonpolar
----
Valine
117
V
Val
Nonpolar
----
Methyl
Aliphatic (Cont’)
Name
MW One
Three
Leucine
131
L
Leu Nonpolar
Isoleucine
131
I
Ile
• Aliphatic-
Structure
Type
R
group
pKa
Nonpolar
Nonaromatic hydrocarbon (H and C only).
– Nonpolar, hydrophobic
• Participate in hydrophobic interactions.
• Usually found inside proteins, away from the aqueous solvent,
----
----
Sulfur Containing (2)
Name
Cysteine
Methionine
Structure
Sulfhydryl
MW
One
121
C
149 M
Three
Type
R
group
pKa
Cys Nonpolar
8.3
Met
----
Nonpolar
• Cysteine may form disulfide bridges, which stabilize 3’
structure.
• Methionine is first amino acid incorporated in growing
peptide during translation.
Aromatic (3)
Name
Phenylalanine
Structure
Phenyl
Tryptophane
Indole
MW
One
Three
Type
165
F
Phe Nonpolar
----
204
W
Trp
----
Nonpolar
R
group
pKa
Aromatic (cont’) (Tyr is also hydroxyl containing)
Name
Tyrosine
Structure
MW
One
Three
Type
R group
pKa
181
Y
Tyr
Polar
10.9
Aromatic
•
•
•
•
May participate in hydrophobic bonding
May bind planar ligands via van der Waals stacking
Absorb Ultraviolet light (approx. 280 n.m.)
Tyrosine may hydrogen bond or donate a proton in catalysis
Hydroxyl Containing (3)
Name
Serine
Threonine
•
•
•
•
Structure
Hydroxyl
MW
One
Three
Type
R group
pKa
105
S
Ser
Polar
----
119
T
Thr
Polar
----
Alcohols or hydroxyl-containing side chains
Proton donors.
Ser is at active site of some enzymes.
Attachment of O-linked carbohydrates to proteins
Acidic (2)
Name
Aspartic Acid
(Aspartate)
Glutamic Acid
(Glutamate)
Structure
MW
One
Three
Type
R
group
pKa
133
D
Asp
Polar
(Acidic)
3.9
147
E
Glu
Polar
(Acidic)
4.3
Carboxylic acid
Carboxylic acid
• Polar – charged (acidic), hydrophilic.
• Found at the Surface of proteins
• Often at active site of enzymes to donate / accept a proton.
Neutral Amide (2)
Name
Asparagine
Glutamine
Structure
Amido
Amido
• Polar – uncharged.
• Participates in hydrogen bonding.
MW
One
Three
Type
R group
pKa
132
N
Asn
Polar
----
146
Q
Gln
Polar
----
Basic (3)
Name
Lysine
Arginine
Structure
MW
One
Three
Type
R group
pKa
146
K
Lys
Polar
(Basic)
10.8
174
R
Arg
Polar
(Basic)
12.5
155
H
His
Polar
(Basic)
6.0
Amino
Guanidinium
Imidazole
Histidine
●
●
Polar – charged (basic), hydrophilic.
Located on the surface. May be involved in catalysis or metal binding.
Amino acids may exist as
stereoisomers
The amino acid alpha carbon is chiral (except G)
• S (sinister) = left = counterclockwise
• R (rectus) = right = clockwise
– Most L amino acids have an S absolute configuration
The charge of an amino acid changes
with pH
Amino acid residues are connected by
peptide bonds
• Peptide bond
– linear and planar
– not free to rotate
• Resonance
– partial double bond characteristics (Can you draw a resonance
structure?)
• Trans
– Hydrogen of the substituted amino group is trans to the
oxygen of the carbonyl group
• exception X-pro
The peptide bond exhibit resonance
and, therefore, possesses double bond
character
• Peptide bond is planar with a bond length of 1.32 Å.
– Intermediate between C-N (1.49 Å) and C=N (1.27 Å)
• Peptide bond is uncharged.
Protein has amino (N) terminal and
carboxyl (C) terminal end
Four Levels of Protein Structure
•
Primary Structure
– linear sequence of amino acids.
• N-met-ala-pro-gly-asp-ala-his -C
•
Secondary Structure
α (alpha) helix
β (beta) sheets
β (beta) turns
Ω (omega) loop
– hydrogen bonding between the carboxyl oxygen
and nitrogen hydrogen of the peptide chain
(back bone)
•
Tertiary Structure
– folding of polypeptide chain as a result of
interactions between R-groups
– A domain is a unit of tertiary structure
•
•
•
•
•
helix turn helix.
helix loop helix
zinc fingers
leucine zipper
Quaternary Structure
– interaction of different polypeptide chains
(subunits) to form a functional protein.
Alpha Helix: type of secondary structure
Proposed by Linus Pauling and Robert Corey (1951)
•
Orientation is right handed helix
•
•
•
Stabilized by hydrogen bonding between
–
–
carbonyl oxygen
NH group of peptide
•
•
every fourth amino acid
3.6 amino acids per turn of helix
–
•
•
Right hand = clockwise
Left hand = counterclockwise
Translation of 1.5 Å and rotation of 100
degrees.
R- groups extend outward
Helix is disrupted by
• proline
• large number of charged amino acids
– (e.g. Q, E, H, K, R)
• amino acids with bulky side chains
– (e.g.W)
• amino acids with branched R groups
– (e.g. V,I)
Helix turn Helix: A type of Domain
Beta Pleated Sheet: type of secondary
structure
Proposed by Pauling and Corey (1951)
•
•
•
•
•
Orientation of proteins is flat or pleated,
linear “sheet” of proteins.
Stabilized by hydrogen bonding between
– Carbonyl oxygen
– NH group of peptide
Adjacent amino acids are separated by
3.5 Å
Strands may organize themselves into
several orientations
– Antiparallel
– Parallel
– Mixed (both antiparrellel and parallel)
Beta bends
– contain proline and glycine
Tertiary Structure
• Tertiary Structure
– folding of polypeptide chain as a result of interactions
between R-groups
Quaternary Structure
• Quaternary Structure
– interaction of different polypeptide chains (subunits) to
form a functional protein.
– Myoglobin will be discussed later along with hemoglobin
– Hemoglobin is a α2β2 tetramer
Denaturing Protein
• unfolding and disorganization of a
proteins secondary and tertiary
structure.
– Does not involve hydrolysis of peptide
bonds
– denaturing agents
• heat
• organic solvents
• Urea
• guanidinium chloride
• detergents
– SDS
• change in pH
– strong acids or bases
• Heavy metals
– Pb or Hg
– Reducing agents
• Beta mercaptoethanol – reduces
disulfide bonds