BMB7010 (2016) St7:8 Ch.1!

Chap. 1 - Biochemistry!
Reading: Stryer (7&8 ed.): Sec: 1.3 + Appendix (We will cover
Sec: 1.1 with Ch.6 & Sec: 1.2 & 1.4 with Ch.4)
Key terms: only terms in the notes/problems/class discussions
Problems: St8: 1, 4, 6, 7, 15, 16, 17, 25, 26
St7: 1, 4, 6, 7, 14, 15, 16, 23, 24
What is biochemistry?

Biochemistry is the study of life processes the chemistry of
carbon molecules that move. It addresses the molecular origin,
evolution, and enhancement of life.

Why study biochemistry?

To cure diseases one must understand the processes in normal cells.

Biochemistry overlaps with genetics, medicine, molecular biology,
microbiology, pharmacology, physiology, and toxicology.

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Biochemistry #2
HOT CAREERS
(The Scientist)
Bioinformatics (We are woefully short of people who
understand both biology and computational approaches Francis Collins, Dir. of the National Institutes of Health)
Proteomics = Detecting and measuring all the proteins
expressed by a genome.
Classical biochemistry: scientists who understand protein
expression, protein purification, enzymology, signaling
pathways , metabolism (recent emphasis on cancer cells)
Translational scientists (M.D. or Ph.D.): bench to
bedside
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DNA, RNA, Proteins

Replication: DNA template, DNA polymerases

Transcription: DNA template, RNA polymerase
Translation: messenger RNA template, aminoacyl transfer
RNA adaptors, ribosomes
Reverse transcription: RNA template, DNA polymerases
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Importance of Proteins
Proteins do many functions in the cell so mutations lead to disease
Alanine-4 mutated to valine in beta-sheet of superoxide dismutase is a cause
of familial Lou Gehrig's disease.
Huntingtons disease and 7 other neurodegenerative diseases are caused by
expanded repeat sequences of glutamine residues.
Cystic fibrosis due to loss of one amino acid out of 1480 in a protein
Proteomics is supplanting genomics
Proteomics: all the proteins expressed by a genome.
Make large amounts of rare proteins. e.g. growth hormone.
80% of biotechnology company research money goes to protein work.
Bioinformatics: About 30-50% of proteins in new genomes are unidentified.
Importance of knowing protein structures
Identifies the amino acids responsible for catalysis and binding. Essential for
mutational studies.
The structure of protein:drug complexes facilitates the design of new drugs.
E.g HIV protease drug resistance studies by Dr. Kovari in the BMB Dept.

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Drug Design!
Canyon Hypothesis:
From the crystal structure of a rhinovirus,
Dr. Rossman proposed:
A crevice or canyon on the virus
binds molecules on the cell surface.
Abs cannot enter the crevice.
Virus residues lining the crevice are
invariant to retain binding.
Virus residues on the outside surface
around the crevice can mutate to block
antibody binding without affecting cell
binding.
HIV
Binding to an immune cell induces a
crevice in the HIV surface protein that
is a new drug target.

CELL

cell 
surface

mutates

constant

VIRUS

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From 1D Sequence to 3D structures

The genetic code equates
each DNA triplet to one
of the 20 amino acids.
The genetic code is
essentially the same for
all organisms
Identical protein
polypeptide chains
spontaneously fold into
identical, well-defined
three dimensional
structures.

Fig. 1.23

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Chemical and Noncovalent Bonds!

Energies in Biochemistry

Interaction

Kcal/mol

Thermal energy

0.6

Van der Waals

Electrostatic bond 3-7

3-7

Hydrogen bond

3-7

Stability of protein
Covalent bond (C-C)

10-20
83

The minimal stability of proteins permits flexibility

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Chemical Bonds
A chemical bond is
formed when adjacent
atoms share a pair of
electrons.
Resonance gives extra
stability (e.g. benzene,
peptide bond) and makes
the structure planar.
Bond/electron pair
movement during
reactions is shown with
arrows

Fig St6: p9
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Electrostatic Bonds!

q1!

r12!

Electrostatic attraction or Coulomb Energy:

E = kq1q2 / D r12
k = 332 for kcal/mol
Negative E attracts, positive E repels.
Dielectric constant, D is variable in proteins.
vacuum = 1
organic solvent = 2
water = 80
protein interior = 2-6
Characteristics
Long range (optimal is 2.8); Enzyme Circe effect.
No angle dependence; decreases with 1/r
Specific, i.e., between two close charges.
Nonspecific interaction with an electrostatic field.
Note: Source of extra stability of proteins from
thermophiles.

q2!

Fig. 1.23

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Hydrogen bonds #1
a hydrogen atom bound to an
electronegative atom (N, O, S) is partially
shared with another electronegative atom
Strength of an H-bond: O>N>>S>C
pH can change the role of a group in
potential H-bonds
H-BOND
DONOR

Fig 1.10

HBOND
ACCEPTOR

STRONGER

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Hydrogen bonds #2!

Characteristics
Specific
Angle dependent - straight (180) are
strongest. No H-bond < 90
Short range - donor to acceptor < 3.5
Update
Can have bifurcated H-bonds
Evidence that CHO=C bond stabilizes
proteins (half an H-bond)

Fig 1.10

Melamine forms an
insoluble, hydrogen-bonded
complex in the kidneys

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Van der Waal's bonds!

Transient asymmetries in the electronic
distribution attract but have repulsion
when the electron clouds overlap.

Characteristics
Non-specific in atom type.
The strength depends on the contact surface
area - about 25 cal/2
No angle dependence
Short range: decreases 1/r6
Weak individually but can be significant
collectively
Gecko
Each foot has 500K hairs that are
divided into 1000 filaments.
Model for self-cleaning sticky
tape.

Fig 1.10

ligand 1

protein
ligand 2

protein

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Effects of Water on Charges

Water is polar
Water molecules have 3.4 H-bonds as a
liquid and 4.0 as ice
Water weakens polar interactions
Electrostatic bonds are weakened because
water has a dielectric constant, D = 80

-

+

Polar = charge separation

Nonpolar = no charge separation
St4Fig

1-13

Fig 1.13: Ice

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Effects of Water on Hydrogen Bonds!

Water weakens H-bonds because it competes for both the donor
and the acceptor.
A H-bond is about 7 kcal/mole in vacuum, but only about 1-5
kcal/mole in water.

Fig St8: pg10

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Thermodynamics: #1
First Law of Thermodynamics
The energy of a system plus the surroundings is constant.
E = the internal energy of the system.
1 calorie = energy to raise 1 g water by 1C or 1K = 4.18 joules.
Second Law of Thermodynamics
A process can occur spontaneously only if the entropy of the universe
(system + surroundings) increases.
S = the change in entropy or degree of randomness. Units = energy/K
Released heat increases kinetic motion/randomness/entropy
Free Energy
Free energy combines the first and second laws for the system alone under
conditions of constant pressure and temperature. (page 12: equation 5)

G = G(products) - G(reactants) = H - TS
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Thermodynamics #2: Free Energy

G = H - TS
H = the change in enthalpy
(heat content) of the system.
H = E + (PV) E in
biological systems where the
pressure and volume do not
change significantly.
The free energy change, G,
must be negative for a reaction
to be spontaneous.
Fig 1.15

Mixing
H 0
S >0

Reacting
H <0.
S <0

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Thermodynamics #3: Order and entropy

GP-R = GP GR < 0

GP-R = GP GR > 0

GP-R = GP GR = (HP HR) T (SP SR)

= HP-R T (SP-R )

To make a more ordered product (SP-R< 0 ), the reaction

must release greater energy/heat into the surroundings
(HP-R <<0)

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Hydrophobic "bond"
Hydrophobic = fears/avoids water; Hydrophilic = likes/prefers water
Hydrophobicity is measured by relative solubilities in ethanol vs water.
See Table 12.2 on page 355. Phe > Met > > Asp > Arg
Nonpolar molecules orient H2O in a cage and decrease the entropy or
disorder of the system, which is unfavorable.
Water excludes the nonpolar molecules because number of waters in cage
around two nonpolar molecules is less than in two separate cages.
Hydrophobic bonds grow stronger with temperature because G -TS.
Strength the buried accessible surface area (~25 cal/mol-1-2).

Fig 1.12

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