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CHAPTER 21: Amino Acids,
Proteins, & Enzymes
General, Organic, & Biological Chemistry
Janice Gorzynski Smith
CHAPTER 21: Amino Acids, Proteins, Enzymes
Learning Objectives:
 The 20 common, naturally occurring Amino Acids
 stereochemistry
 acid/base chemistry
 Peptides
 Formation
 N & C terminals
 Proteins
 Primary, Secondary, Tertiary, Quaternary structure
 Hydrolysis and denaturation
 Enzymes
 Catalysis
 Inhibitors
 Zymogens
CH 21 Homework:
End of Chapter problems: 32, 36, 38, 42, 48, 50, 52, 62, 64, 68, 70, 74,
Smith, Janice Gorzynski. General, Organic,
77, 81, 93, 94
& Biological Chemistry 2nd Ed.
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Amino Acids
Definition
All amino acids contain two functional groups—an
amino group (NH2) and a carboxyl group (COOH).
Amino acids differ in the R group bonded to the α carbon
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Amino Acids
At isoelectric pH
• The isoelectric point for amino acids is about 6, this is
the pH at which the amino acid exists as a neutral
molecule
• The pKa of the amine group is usually about 9-11
• The pKa of the carboxylic acid group is usually about 2-3
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Amino Acids
Acid/Base Chemistry
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Amino Acids
Stereochemistry
• Carbohydrates: naturally occurring isomer is the Disomer (OH group on right in a Fischer projection)
• Amino Acids: most naturally occurring isomers are the Lisomer (NH3 group on the left in a Fischer projection)
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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The 20 common &
naturally
occurring amino
acids in humans.
Essential Amino Acids:
Isoleucine (Ile)
Leucine (Leu)
Methionine (Met)
Phenylalanine (Phe)
Threonine (Thr)
Tryptophan (Trp)
Valine (Val)
Arginine (Arg)
Histidine (His)
Lysine (Lys)
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Peptides
Definition
•Peptides and proteins are formed when amino
acids are joined together by amide bonds.
•A dipeptide has two amino acids joined together
by one amide bond.
•The amide bond is called
a peptide bond.
•Polypeptides have many amino acids, while
proteins have more than 40 amino acids.
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Peptides
Amide Bond Formation
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Peptides
Amide Bond Formation
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Peptides
N & C Terminal Amino Acids
•The amino acid with the free –NH3+ group is the
N-terminal amino acid and is written on the left.
•The amino acid with the free –COO− group is the
C-terminal amino acid and is written on the right.
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Peptides/Prote
in
Insulin
Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser-Ile-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-R
Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-GlyGlu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Thr-R’
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Primary Structure
The primary structure of a protein is the sequence
of amino acids joined together by peptide bonds.
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Secondary Structure
•The secondary structure is the 3D arrangement of localized regions of a
protein.
•These regions arise due to hydrogen bonding between the N—H group
of one amide with the C═O group of another.
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Secondary Structure
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Tertiary Structure
The tertiary structure is the 3D shape adopted by the entire
peptide chain:
• Maximize Hydrogen bonding with water (hydrophilic)
• Stabilize non-polar sidechains by london dispersion forces
(hydrophobic)
• Polar functional groups H-bond with each other
• Charged sidechains attracted through electrostatic interactions
• Disulfide bonds form
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Tertiary Structure
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Quaternary Structure
The quaternary structure of the protein is the shape
adopted when two or more folded poly-peptide chains come
together into one complex. Ex: Potassium Channel:
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Quaternary Structure
Hemoglobin
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Quaternary Structure
Hemoglobin
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
1°, 2°, 3°, 4° Structure
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Peptide Hydrolysis
Protein hydrolysis involves breaking the peptide bonds by
treatment with aqueous acid, base, or certain enzymes: Pepsin
(gastric juices), Trypsin and Chymotrypsin (intestines)
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Proteins
Peptide Denaturation
Denaturation is the process of altering the shape of a protein
without breaking the amide bonds that form the primary
structure: heat, acid, base, or agitation
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Enzymes
Definition
Enzymes are proteins that serve as biological catalysts
for reactions in all living organisms.
• They increase the rate of a reaction (106 to 1012 times faster),
but are unchanged themselves.
• Enzymes are very specific; each enzyme catalyzes a certain
reaction or type of reaction only.
• The names of most enzymes end with the suffix “-ase” like
peptidase, lipase, and hydrolase
• A cofactor is a metal ion or an organic molecule needed for an
enzyme-catalyzed reaction to occur.
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Enzymes
Function
http://leavingbio.net/enzymes.htm
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Enzymes
Conformational Changes Upon Binding
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http://plantcellbiology.masters.grkraj.org/html/Plant_Cell_Biochemistry_And_Metabolism1-Proteins_And_Enzymes.htm
Enzymes
Inhibition
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http://o.quizlet.com/i/WRLW8kdWLDOY1YZbEdKgyA_m.jpg
Enzymes
HIV Protease Inhibitor
Protease inhibitors are designed to
mimic a peptide linkage (-NH-CO-)
but replaces the linkage with a
–CH2-CH(OH)- which binds to the
active site but the protease cannot
cleave a linkage so it stays bound.
Saquinavir:
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http://en.wikipedia.org/wiki/Discovery_and_development_of_HIV-protease_inhibitors
Enzymes
Lipoxygenase Inhibitor
Zileuton is an asthma maintenance
medication that inhibits 5-lipoxygenase,
therefore, inhibiting leukotriene
formation.
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http://en.wikipedia.org/wiki/Zileuton
Enzymes
Differences in Binding Sites
Superoxide Dismutase: SOD
Hydrophobic Binding Pocket
Superoxide Reductase: SOR
Hydrophilic Binding Pocket
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Mechanistic Differences: SOR vs SOD
Enzymes
OH
OAsp FeIII
O2 -
NHis
OH
NHis
O2-
H+
O2
NHis
SOD Mechanism
OH2
NHis
OAsp FeIII
OAsp FeII
NHis
NHis
NHis
NHis
OH2
HOOH
H+
NHis
2H+
OAsp FeII
NHis
NHis
O2
H2O
SOR Mechanism
-
O2NHis
* O2- hydrogen bonds to residues in secondary
coordination sphere, positioning it near Fe(II),
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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Enzymes
Zymogens
Smith, Janice Gorzynski. General, Organic,
& Biological Chemistry 2nd Ed.
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