ReadingChapter 14

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Reading Chapter 14 Homework Chapter 13 due
today 7 pm. Chapter 14 problems due Friday 5
pm. 14.1, 14.2a, 14.3a, 14.4, 14.5, 14.10,
14.31, 14.34, 14.35 14.38, 14.39, 14.44,
14.45, 14.51, 14.77 Quiz Due Friday 5 pm.
No extensions Final Exam Friday December 11,
2009. No makeups Section 1, 800 am
Section 2, 1010 am Review Session Tuesday,
December 8 at 6 pm, Science 313
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Enzymes Are a Large Class of Proteins

• Generally very substrate specific. Can be
  stereospecific.
• Operate under specific conditions pH optimum,
  temperature optimum
• Most near pH 7.4, 37 C, though some differ
• e.g. pepsin at pH 1.5, found in stomach
• May require cofactors ions or organic
  compounds
• Zn2 (alcohol dehydrogenase, metalloproteases)
• Fe2 (peroxidases)
• NADH, NAD
• FADH2, FAD
• CoA

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Enzymes Catalyze Biochemical Reactions by
Lowering Their Activation Energy
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Many Drugs Are Enzyme Inhibitors
Atorvastatin (Lipitor) HMG-CoA reductase
inhibitor Lowers LDL cholesterol
Celecoxib (Celebrex) COX-2 inhibitor Reduces
prostaglandin synthesis (NSAID)
Acetazolamide (Diamox) Carbonic anhydrase
inhibitor Increases loss of bicarbonate via
urine (treatment for alkalosis)
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Competitive Enzyme Inhibitors Bind Enzyme Active
Site
Competitive enzyme inhibitors generally have
similar chemical structure as endogenous substrate
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Methotrexate is an Example of a Competitive
Enzyme Inhibitor
Competitive inhibitor of DHFR
Methotrexate (MTX) Inhibits dihydrofolate
reductase Anticancer agent (leukemia) Antiinflamma
tory (rheumatoid arthritis)
Folic acid (vitamin B9) Important in pregnancy
and infancy Rapidly dividing cells
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Non-Competitive Inhibitors Bind Allosteric Site
on Enzyme
Substrate
Enzyme
Substrate
Enzyme-inhibitor complex
Inhibitor
Conformational change
Non-competitive enzyme inhibitors generally have
distinct chemical structure from endogenous
substrate.
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Non-Competitive Inhibitors Bind Allosteric Site
on Enzyme
Acetylcholine Neurotransmitter Substrate for
acetylcholinesterase
Tacrine (Cognex) Alzheimers disease Inhibits
acetylcholinesterase
Non-competitive inhibitor of acetylcholinesterase
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ATP-Competitive Kinase Inhibitors For Cancer
Treatment
Ras-Raf-MEK-ERK Signaling Pathway Is Involved in
Cell Proliferation and Cell Survival
Raf and MEK inhibitors in clinical trials
Binding of epidermal growth factor to receptor
initiates cascade of signaling events leading to
cell division.
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Nucleic acids Nucleic acids are chains of
nucleotide residues Deoxyribonucleic acid
(DNA) Ribonucleic acid (RNA)
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Nucleic Acids are Ubiquitous in Living Organisms

• Found in all cells and viruses
• DNA is the blueprint of cells. Long-term
  storage of genetic information.
• RNA is involved in transcribing DNA into
  proteins.

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Nucleic Acids Are Assembled From Nucleotides
Nucleotide structure Base Sugar Phosphate
RNA only
DNA only
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Polynucleotides Are Covalently Linked via
3,5-Phosphodiester Bonds
Thymine (T)
Adenine (A)
Phosphodiester linkage
Cytosine (C)
Guanine (G)
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Deoxyribonucleic Acid and Ribonucleic Acid Differ
in Sugar and Base Units
Ribonucleic acid (RNA)
Deoxyribonucleic acid (DNA)
Ribose residue
Deoxyribose residue
Thymine base
Uracil base
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Nucleotide Nomenclature is Wordy... Hence
Abbreviations
Deoxyguanosine 5-monophosphate (dGMP)
Adenosine 5-triphosphate (ATP)
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DNA Structure

• Primary structure Sequence of nucleotide
  residues, read from 5 to 3.
• Adenine (A), Cytosine (C), Thymine (T), Guanine
  (G)
• Example dTGCA
• d deoxy (DNA)
• (5 end) Thymine-Guanine-Cytosine-Adenine (3
  end)
• Secondary structure Antiparallel double
  stranded DNA helix.
• Antiparallel one strand is 5 to 3, other
  strand is 3 to 5
• Tertiary structure Overall three-dimensional
  shape.

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Antiparallel Double Stranded DNA
Antiparallel strands (5-3 and 3-5)
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DNA Double Helix is Held Together by Hydrogen
Bonds
H-bond donor NH
H-bond acceptor O
H-bond acceptor O
H-bond donor NH
Complementary base pairing specific hydrogen
bonds formed between bases
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DNA Tertiary Structure
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DNA in Cells

• A chromosome is a single piece of coiled DNA.
• Each cell in the human body (except red blood
  cells) contain a copy of all the bodys
• genes in its DNA.
• 23 pairs of chromosomes in cells. Of each pair
  one from father, one from mother.
• Prior to cell division, each chromosome must be
  copied (DNA replication).

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Transfer of Information From DNA to Proteins