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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:
q  The 20 common, naturally occurring Amino Acids q  stereochemistry q  acid/base chemistry q  PepFdes q  FormaFon q  N & C terminals q  Proteins q  Primary, Secondary, TerFary, Quaternary structure q  Hydrolysis and denaturaFon q  Enzymes q  Catalysis q  Inhibitors q  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. 2 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. 3 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. 4 Amino Acids
Acid/Base Chemistry
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 5 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. 6 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)
7 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. 8 Peptides
Amide Bond Formation
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 9 Peptides
Amide Bond Formation
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 10 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. 11 Peptides/
Protein
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. 12 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. 13 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. 14 Proteins
Secondary Structure
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 15 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. 16 Proteins
Tertiary Structure
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 17 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. 18 Proteins
Quaternary Structure
Hemoglobin
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 19 Proteins
Quaternary Structure
Hemoglobin
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 20 Proteins
1°, 2°, 3°, 4° Structure
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 21 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. 22 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. 23 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. 24 Enzymes
Function
hUp://leavingbio.net/enzymes.htm 25 Enzymes
Conformational Changes Upon Binding
hUp://plantcellbiology.masters.grkraj.org/html/Plant_Cell_Biochemistry_And_Metabolism1-­‐Proteins_And_Enzymes.htm 26 Enzymes
Inhibition
27 hUp://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:
28 hUp://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.
29 hUp://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. 30 Mechanistic Differences: SOR vs SOD
Enzymes
OH
OAsp FeIII
O2-
OH
NHis
NHis
O2-
H+
O2
NHis
SOD Mechanism
OH2
NHis
OAsp FeIII
NHis
OAsp FeII
NHis
NHis
OH2
HOOH
H+
2H+
OAsp FeII
NHis
NHis
O2
H 2O
NHis
-
O2NHis
N
* O2- hydrogen bonds to residues in secondary
coordination sphere, positioning it near Fe(II),
SOR Mechanism
NHis
His
e–
SCys
II NHis
Fe
N
His
NHis
His
OH–
N
SCys
III
NHis
Fe
NHis
N
OH
HOOH
OH–
His
His
N
NHis
N
O
H2O
RCO2–
O2–, H+
SCys
III
NHis
Fe
Glu14–CO2–, H+
H2O
SCys
His
III
His
Fe N
His
N
NHis
O
O
N
Glu14
HO
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 31 Enzymes
Zymogens
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 32