Spring Quarter 2003 Chem 375 BioChemistry

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Spring Quarter 2003 Chem 375 BioChemistry

• Instructor Spencer Anthony-Cahill
• Office CB440
• Office hrs TBA
• sacahill_at_chem.wwu.edu
• http//www.chem.wwu.edu/sacahill/375/

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What is Biochemistry?

• the systematic torture of students with copious
  incomprehensible jargon, cryptic fomulae, and
  impossible insoluble problems.
• Biochemistry is the study of Life as a process
  that can be understood
• Primary Objective understand the molecular
  mechanisms that constitute the living state
  (Molecular Logic)

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Apply Biochemical Understanding to

• advances in medicine and healthcare (gene
  therapy, biopharmaceuticals, diagnostics)
• explain the biological responses to environmental
  signals (chemical toxicity, hormone action)
• agricultural practices (crop protection, animal
  husbandry)

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What is Biochemistry?

• Biochemistry is the study of Life as a process
  that can be understood

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How Does Science Describe the Living State?

• Organisms must extract energy from their
  environment
• Possess ability to self-replicate and
  self-assemble
• Ability to adapt to change

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Lehninger Molecular Logic

• A living cell is a self-assembling,
  self-regulating, self-replicating isothermal open
  system of organic molecules operating on a
  principle of maximum economy of parts and
  processes it promotes many consecutive, linked
  organic reactions for the transfer of energy and
  for the synthesis of its own components by means
  of organic catalysts that it produces itself.
• Biol/Chem 471 Biol/Chem 472 Biol/Chem 473

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How does science describe the living state?
atoms, subatomic particlesthe undiscovered
smaller organic molecules
Biopolymers/Macromolecules
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See VVP Fig 1-8
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Phosphatidyl choline
Polar headgroup
Hydrophobic tail
VVP Figs 9-1, 9-4
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VVP Figs 9-17, 9-18
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DG DH - TDS

• If DG is the reaction is
• gt 0 thermodynamically unfavorable (reverse
  reaction is favorable)
• 0 at equilibrium (forward and reverse
  reactions equally favorable)
• lt 0 thermodynamically favorable as written

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Blue turbulence chaos and order
WATER!!!
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Fig 2-1 in VVP
Net dipole moment for water
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Lone pair electrons
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Fig 2-8 in VVP
Highly ordered water molecules at interface
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DG DH - TDS

• If DG is the reaction is
• gt 0 thermodynamically unfavorable (reverse
  reaction is favorable)
• 0 at equilibrium (forward and reverse
  reactions equally favorable)
• lt 0 thermodynamically favorable as written

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See Table 21 in VVP
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See Fig 2-5 in VVP
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DG DGo' RTlnQ

• If Q is then DG is
• gt Keq gt0 (reverse reaction is favorable)
• Keq 0 (at equilibrium)
• lt Keq lt0 (reaction favorable as written)

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Standard States in Biochemistry 1. Activity of
water is 1. (really 55 M) 2. Hydrogen ion
activity is 1 at pH 7. ?Go
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13-2
Table 13-2 p 362 in VVP
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Acids, Bases and Buffers!!!

• pH pKa log A
• HA

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Bloody Fact

• If 1 mL of 10 N HCl is added to 1 liter of saline
  solution at pH 7.0, the pH will decrease to
  roughly pH 2.
• If 1 mL of 10 N HCl is added to 1 liter of blood
  plasma at pH 7.4, the pH will decrease to pH
  7.2.
• Why? Blood is buffered (in this case by the
  H2CO3/HCO3 system).

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VVP Table 4-1
0.091
X
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VVP Fig 2-15
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Buffers!!!

• pH pKa log A
• HA

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This is IMPORTANT!!!

• If pH pKa, then A- HA
• then deprotonated protonated
• If pH lt pKa, then A- lt HA
• then deprotonated lt protonated
• If pH gt pKa, then A- gt HA
• then deprotonated gt protonated

Summarized on VVP Fig 2-15
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Using Henderson-Hasselbalch

• at pH values 3 pH units from pKa the group is
  essentially fully deprotonated or fully
  protonated, so the average charge 0 or 1.
• at pH pKa the group is 50 protonated, thus it
  carries an average charge 0.5
• H-H equation can be used to calculate the average
  charge on an ionizable group at any pH.

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VVP Fig 2-16
pHpKa3
pHpKa2
pHpKa1
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Ionic properties of amino acids impart ionic
properties to proteins

• in general these are SURFACE properties (i.e.
  charged sidechains are on solvent-exposed outside
  of folded structure)
• affect protein-ligand binding (e.g. DNA-binding
  proteins) or catalysis
• average charge on protein is an important
  consideration in the design of a purification
  process

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BUILDING BLOCKS!!! NUCLEOTIDES AMINO ACIDS
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amino acid structures
See Table 4-1 p80 in VVP
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See Table 4-1 p80 in VVP
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Models
models
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Amino acid structures
http//info.bio.cmu.edu/Courses/ BiochemMols/AAVie
wer/ AAVFrameset.htm
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Ionic properties of amino acids impart ionic
properties to proteins

• in general these are SURFACE properties (i.e.
  charged sidechains are on solvent-exposed outside
  of folded structure)
• affect protein-ligand binding (e.g. DNA-binding
  proteins) or catalysis
• average charge on protein is an important
  consideration in the design of a purification
  process

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pKa3
pKa2
pKa1
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See VVP Fig 4-3
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VVP Fig 6-3 p 126
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(Rasmol)
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Other Properties of Amino Acids

• Stereochemistry (all biosynthetic proteins made
  up of L-isomer)
• Hydropathy (partitioning between polar and
  nonpolar solvents as indicator of polarity) (see
  Table 6-2 in VVP p 150 Take Note p58)
• these two properties are major determinants of
  peptide conformation

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Example of a protein sequence
N-terminus

• MANSKINKQL DKLPENLRLN GRTPSGKLRS FVCEVCTRAF
  ARQEHLKRHY
• RSHTNEKPYP CGLCNRCFTR RDLLIRHAQK IDSGNLGETI
  SHTKKVSRTI
• TKARKNSASS VKFQTPTYGT PDNGGSGGTV LSEGEWQLVL
  HVWAKVEADV
• AGHGQDILIR LFKSHPETLE KFDRFKHLKT EAEMKASEDL
  KKHGVTVLTA
• LGAILKKKGH HEAELKPLAQ SHATKHKIPI KYLEFISEAI
  IHVLHSRHPG
• DFGADAQGAM NKALELFRKD IAAKYKELGY G

C-terminus
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VVP page 150
nonpolar
polar
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VVP Fig 6-1 p 125
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VVP Fig 5-1 p 94
C-termini
N-termini