Download amino acids

Two notable breakthroughs in the
history of biochemistry
(1) Discovery of the role of enzymes as
catalysts
(2) Identification of nucleic acids as
information molecules
Flow of information: from nucleic acids to proteins
DNA
RNA
Protein
1.2 The Chemical Elements of
Life
• Only six nonmetallic elements: oxygen, carbon,
hydrogen, nitrogen, phosphorous, and sulfur
account for >97% of the weight of most organisms
• These elements can form stable covalent bonds
• Water is a major component of cells
• Carbon is more abundant in living organisms than
it is in the rest of the universe
Fig 1.1 Periodic Table of the
elements
• Important elements found in living cells are
shown in color
• The six abundant elements are in red
(CHNOPS)
• Five essential ions are in purple
• Trace elements are in dark blue (more
common) and light blue (less common)
Fig 1.2 (a) General formulas
Fig 1.2(b) General
Formulas
Fig 1.2 (c) General Formulas
A. Proteins
• Proteins are composed of 20 common amino acids
• Each amino acid contains:
(1) Carboxylate group (-COO-)
(2) Amino group (-NH2)
(3) Side chain (R) unique to each amino acid
Fig 1.3 Structure of an amino acid
and a dipeptide
(a) Amino group (blue), carboxylate group (red)
(b) Dipeptides are connected by peptide bonds
Polypeptides
• Polypeptides - amino acids joined end to end
• Conformation - the three dimensional shape of
a protein which is determined by its sequence
• Active site - a cleft or groove in an enzyme that
binds the substrates of a reaction
Fig 1.4 Egg white lysozyme
(a) Free enzyme
(b) Enzyme, bound substrate in active site cleft
B. Polysaccharides
• Carbohydrates, or saccharides, are
composed primarily of C,H and O
• Polysaccharides are composed of saccharide
monomers
• Most sugar structures can be represented as
either linear (Fischer projection) or cyclic
Fig 1.5 Representations of the
structure of ribose
(a) Glucose, (b) Cellulose
Glycosidic bonds
connecting glucose
residues are in red
C. Nucleic Acids
• Polynucleotides - nucleic acid biopolymers
are composed of nucleotide monomers
• Nucleotide monomers are composed of:
(1) A five-carbon sugar
(2) A heterocyclic nitrogenous base
(3) Phosphate group(s)
Fig 1.7 Deoxyribose
• Deoxyribose lacks a hydroxyl group at C-2.
It is the sugar found in DNA.
Nitrogenous bases
• Major Purines:
Adenine (A)
Guanine (G)
• Major Pyrimidines
Cytosine (C)
Thymine (T)
Uracil (U)
Fig 1.8 Adenosine
Triphosphate (ATP)
• Nitrogenous base (adenine), sugar (ribose)
Structure of a dinucleotide
• Residues are
joined by a
phosphodiester
linkage
Short segment of a DNA
molecule
• Two polynucleotides
associate to form a
double helix
• Genetic information is
carried by the sequence
of base pairs
D. Lipids and Membranes
• Lipids are rich in carbon and hydrogen, but
contain little oxygen
• Lipids are not soluble in water
• Fatty acids are the simplest lipids: long chain
hydrocarbons, a carboxylate group at one end
• Fatty acids are often components of
glycerophospholipids
Structures of (a) glycerol 3-phosphate, (b) a
glycerophospholipid
Model of a membrane lipid
• Hydrophilic (water-loving)
head interacts with H2O
• Hydrophobic (waterfearing) tail
Fig 1.13 Structure of a biological
membrane
• A lipid bilayer with associated proteins
The Cell is the Basic Unit of Life
• Plasma membrane - surrounds aqueous
environment of the cell
• Cytoplasm - all materials enclosed by the
plasma membrane (except the nucleus)
• Cytosol - aqueous portion of the
cytoplasm minus subcellular structures
• Bacteriophage or phage - viruses that
infect prokaryotic cells
Prokaryotic Cells: Structural Features
• Prokaryotes, or bacteria are usually singlecelled organisms
• Prokaryotes lack a nucleus (their DNA is
packed in a nucleoid region of the cytoplasm)
• Escherichia coli (E. coli) - one of the best
studied of all living organisms
• E. coli cells are ~0.5µm diameter, 1.5µm long
E. coli cell
Eukaryotic Cells: Structural Features
• Eukaryotes: plants, animals, fungi, protists
• Have a membrane-enclosed nucleus containing
the chromosomes
• Are commonly 1000-fold greater in volume than
prokaryotic cells
• Have an intracellular membrane network that
subdivides the interior of the cell
(a) Eukaryotic cell (animal)
Fig 1.15(b) Eukaryotic cell
(plant)
A. The Nucleus
Nuclear envelope and endoplasmic
reticulum of a eukaryotic cell
B. Endoplasmic Reticulum and
Golgi Apparatus
• Endoplasmic reticulum - network of
membrane sheets and tubules extending from
the nucleus
• Golgi apparatus - responsible for modification
and sorting of some biomolecules.
Golgi apparatus
C. Mitochondria and
Chloroplasts
• Mitochondria are the main sites of energy
transduction in aerobic cells.
Chloroplasts - sites of photosynthesis in
plants, green algae
D. Specialized Vesicles
• Lysosomes - contain specialized digestive
enzymes
• Peroxisomes - carry out oxidative reactions in
animal and plant cells
• Vacuoles - fluid-filled vesicles, used as storage
sites for water, ions and nutrients such as glucose
Fig 1.16
Fluorescently labeled:
(a) Actin filaments
(b) Microtubules
Ionic and Polar Substances
Dissolve in Water
• Hydrophilic (water-loving) substances (polar
and ionic (electrolytes)) readily dissolve in H2O
• Polar water molecules align themselves around
ions or other polar molecules
• A molecule or ion surrounded by solvent
molecules is solvated
• When the solvent is water the molecules or ions
are hydrated
Solubilities of molecules in
water
• Solubility in water depends upon the ratio
of polar to nonpolar groups in a molecule
• The larger the portion of nonpolar groups
the less soluble the molecule is in water
• The larger the portion of polar groups
(e.g. hydroxyl groups (-OH)) the more
soluble the molecule is in water
Fig. 2.7 Structure of
glucose
• Glucose has five hydroxyl
groups and a ring oxygen
which can hydrogen bond
• Glucose is very soluble in
water
Nonpolar Substances Are
Insoluble in Water
• Hydrophobic (water-fearing) molecules are
nonpolar
• Hydrophobic effect - the exclusion of nonpolar
substances by water (critical for protein folding
and self-assembly of biological membranes)
• Amphipathic molecules have hydrophobic
chains and ionic or polar ends. Detergents
(surfactants) are examples.
Sodium dodecyl sulfate (SDS)
• A synthetic detergent
• A 12-carbon tail
• Polar sulfate group
Detergents in water
• Monolayers can form on
the surface
• At higher concentrations
detergents can form
micelles
Noncovalent Interactions in
Biomolecules
Weak noncovalent interactions are important in:
• Stabilization of proteins and nucleic acids
• Recognition of one biopolymer by another
• Binding of reactants to enzymes
Noncovalent forces
There are four major types of noncovalent forces:
(1) Charge-charge interactions
(2) Hydrogen bonds
(3) Van der Waals forces
(4) Hydrophobic interactions
A. Charge-Charge Interactions
(Ion Pairing)
• Electrostatic interactions between two charged
particles
• Can be the strongest type of noncovalent forces
• Can extend over greater distances than other
forces
• Charge repulsion occurs between similarly
charged groups
Types of attractive charged
interactions
• Salt bridges - attractions between oppositelycharged functional groups in proteins
• Ion pairing - a salt bridge buried in the
hydrophobic interior of a protein is stronger than
one on the surface
B. Hydrogen Bonds
• Among the strongest of noncovalent interactions
• H atom bonded to N, O, S can hydrogen bond to
another electronegative atom (~0.2 nm distance)
• Total distance between the two electronegative
atoms is ~0.27 to 0.30 nm
• In aqueous solution, water can H-bond to exposed
functional groups on biological molecules
Fig. 2.10
(a) Hydrogen bonding
between A-H and B
(b) Some biologically
important H-bonds
Hydrogen bonding between
complementary bases in DNA
C. Van der Waals Forces
• Weak short range forces between:
(a) Permanent dipoles of two uncharged molecules
(b) Permanent dipole and an induced dipole
in a neighboring molecule
• Although individually weak, many van der Waals
interactions occur in biological macromolecules and
participate in stabilizing molecular structures
D. Hydrophobic Interactions
• Association of a relatively nonpolar molecule or
group with other nonpolar molecules
• Depends upon the increased entropy (+∆S)
which occurs when water molecules
surrounding a nonpolar molecule are freed to
interact with each other in solution
• The cumulative effects of many hydrophobic
interactions can have a significant effect on the
stability of a macromolecule
Noncovalent interactions in
biomolecules
• Charge-charge interactions
• Hydrogen bonds
• Van der Waals interactions
• Hydrophobic interactions
Water Is Nucleophilic
• Nucleophiles - electron-rich atoms or groups
• Electrophiles - electron-deficient atoms or groups
• Water is a relatively weak nucleophile
• Due to its high cellular concentration, hydrolysis
reactions in water are thermodynamically favored
Hydrolysis of a peptide
Condensation reactions can
be favorable in cells
• ATP chemical energy can be used to drive reactions
• Glutamine synthetase catalyzes a condensation
reaction
2.7 Ionization of Water
• Pure water consists of a low concentration of
hydronium ions (H3O+) and an equal
concentration of hydroxide ions (OH-)
• Acids are proton donors (e.g. H3O+) and bases
are proton acceptors (e.g. OH-)
2.8 The pH Scale
• pH is defined as the negative logarithm
of the concentration of H+
Table 2.3
pH values for
some fluids
• Lower values are
acidic fluids
• Higher values
are basic fluids
Acid Dissociation Constants
of Weak Acids
• Strong acids and bases dissociate
completely in water
HCl + H2O
Cl- + H3O+
• Cl- is the conjugate base of HCl
• H3O+ is the conjugate acid of H2O
Acetic acid is a weak acid
• Weak acids and bases do not dissociate
completely in H2O
The Henderson-Hasselbalch
Equation
• Defines the pH of a solution in terms of:
(1) The pKa of the weak acid
(2) Concentrations of the weak acid
(HA) and conjugate base (A-)
Table 2.4
Buffered Solutions Resist Changes in pH
• Buffer capacity is the ability of a solution to resist
changes in pH
• Most effective buffering occurs where:
solution pH = buffer pKa
• At this point: [weak acid] = [conjugate base]
• Effective buffering range is usually at pH values
equal to the pKa ± 1 pH unit
Regulation of pH in the blood of
animals
• Blood plasma of mammals has a constant pH
which is regulated by a buffer system of:
carbon dioxide /carbonic acid /bicarbonate
• Buffer capacity depends upon equilibria between:
(1) Gaseous CO2 (air spaces of the lungs)
(2) Aqueous CO2 (dissolved in the blood)
(3) Carbonic acid
(4) Bicarbonate
Percentages of carbonic acid and its
conjugate bases as a function of pH
Fig.
2.21
Regulation of the pH
of blood in mammals
3.1 General Structure of
Amino Acids
• Twenty common α-amino acids have carboxyl
and amino groups bonded to the α-carbon atom
• A hydrogen atom and a side chain (R) are also
attached to the α-carbon atom
Zwitterionic form of amino
acids
• Under normal cellular conditions amino
acids are zwitterions (dipolar ions):
Amino group =
Carboxyl group =
-NH3+
-COO-
A. Aliphatic R Groups
• Glycine (Gly, G) - the α-carbon is not chiral
since there are two H’s attached (R=H)
• Four amino acids have saturated side chains:
Alanine (Ala, A) Valine (Val, V)
Leucine (Leu, L) Isoleucine (Ile, I)
• Proline (Pro, P) 3-carbon chain connects
α-C and N
Four aliphatic amino acid
structures
Proline has a nitrogen in the
aliphatic ring system
• Proline (Pro, P) - has a three
carbon side chain bonded to
the α-amino nitrogen
• The heterocyclic pyrrolidine
ring restricts the geometry of
polypeptides
B. Aromatic R Groups
• Side chains have aromatic groups
Phenylalanine (Phe, F) - benzene ring
Tyrosine (Tyr, Y) - phenol ring
Tryptophan (Trp, W) - bicyclic indole group
Aromatic amino acid structures
C. Sulfur-Containing R Groups
• Methionine (Met, M) - (-CH2CH2SCH3)
• Cysteine (Cys, C) - (-CH2SH)
• Two cysteine side chains can be cross-linked
by forming a disulfide bridge (-CH2-S-S-CH2-)
• Disulfide bridges may stabilize the threedimensional structures of proteins
Methionine and cysteine
Proteins: Three
Dimensional Structure and Function
• Conformation - three dimensional shape
• Native conformation - each protein folds into a
single stable shape (physiological conditions)
• Biological function of a protein depends
completely on its native conformation
• A protein may be a single polypeptide chain or
composed of several chains
D. Side Chains with Alcohol
Groups
• Serine (Ser, S) and Threonine (Thr, T) have
uncharged polar side chains
E. Basic R Groups
• Histidine (His, R) - imidazole
• Lysine (Lys, K) - alkylamino group
• Arginine (Arg, R) - guanidino group
• Side chains are nitrogenous bases which are
substantially positively charged at pH 7
Structures of histidine, lysine and
arginine
F. Acidic R Groups and Amide
Derivatives
• Aspartate (Asp, D) and Glutamate (Glu, E)
are dicarboxylic acids, and are negatively
charged at pH 7
• Asparagine (Asn, N) and Glutamine (Gln, Q)
are uncharged but highly polar
Structures of aspartate, glutamate,
asparagine and glutamine
Compounds derived from common
amino acids
Column Chromatography
(a) Separation of a
protein mixture
(b) Detection of
eluting protein
peaks
Electrophoresis
• Polyacrylamide gel electrophoresis (PAGE)
Separates molecules on a polyacrylamide gel
matrix when an electric field is applied
• SDS-PAGE. Sodium dodecyl sulfate (SDS)
coats proteins with negative charges. Coated
polypeptide chains then separate by molecular
mass (method to determine molecular weight)
(a) SDS-PAGE Electrophoresis
(b) Protein banding pattern after run
Types of proteins
• Proteomics - study of large sets of proteins,
such as the entire complement of proteins
produced by a cell
• E. coli has about 4000 different polypeptides
(average size 300 amino acids, Mr 33,000)
• Fruit fly (Drosophila melanogaster) about 16,000,
humans, other mammals about 40,000 different
polypeptides
E. coli proteins on 2D gel electrophoresis
Globular proteins
• Usually water soluble, compact, roughly
spherical
• Hydrophobic interior, hydrophilic surface
• Globular proteins include enzymes,carrier
and regulatory proteins
Fibrous proteins
• Provide mechanical support
• Often assembled into large cables or threads
• α-Keratins: major components of hair and nails
• Collagen: major component of tendons, skin,
bones and teeth
Antibodies Bind Specific Antigens
• Vertebrate immune systems synthesize protein
antibodies (immunoglobulins) to eliminate
bacteria, viruses, other foreign substances
• Antibodies specifically recognize and bind antigens
• Antibodies are synthesized by lymphocytes (white
blood cells)
Fig 4.52 (a) Human antibody
structure
Fig. 4.52
(b)
• Heavy chains
(blue) and light
chains (red)
• Disulfide bonds
(yellow)
• Variable
domains colored
darker
Structural and Functional
Diversity of Lipids
• Fatty acids - R-COOH (R=hydrocarbon chain)
are components of triacylglycerols,
glycerophospholipids, sphingolipids
• Phospholipids - contain phosphate moieties
• Glycosphingolipids - contain both sphingosine
and carbohydrate groups
• Isoprenoids - (related to the 5 carbon isoprene)
include steroids, lipid vitamins and terpenes
Structure and nomenclature
of fatty acids
Glycerophospholipids
• The most abundant lipids in membranes
• Possess a glycerol backbone
• A phosphate is esterified to both glycerol and
another compound bearing an -OH group
• Phosphatidates are glycerophospholipids with
two fatty acid groups esterified to C-1 and C-2
of glycerol 3-phosphate
(a) Glycerol 3-P and (b) phosphatidate
Structures of glycerophospholipids
(next slide)
(a) Phosphatidyl ethanolamine
(b) Phosphatidyl serine
(c) Phosphatidylcholine
• Functional groups from esterified alcohols
are shown in blue
• General names refer to a family of
compounds
Fig 9.9 Phospholipases hydrolyze
phospholipids
Structure of an
ethanolamine plasmalogen
• Plasmalogens - C-1
hydrocarbon substituent
attached by a vinyl ether
linkage (not ester linkage)
Structure of a typical eukaryotic
plasma membrane
Characteristics of
membrane transport