Morning recap - 29

Morning recap - 29

1. DNA replication

2. Drug elimination

   • Two different phases
     • Phase 1
       • Metabolism
         • Cp450
           • Metabolises many drugs
             • Oxidises
               • Reduces
                 • Hydrolyses
             • Produces cytotoxic compounds
             • Some drugs have longer functions as their metabolites also have the same effect
             • Some drugs - only their metabolites are active
             • Some drugs their metabolites have completely different functions
         • Drugs that compete for the same metabolising enzyme therefore they will act longer
         • Drugs that inhibit other drugs metabolising enzymes
         • Drugs that enhance other drugs metabolising enzymes
     • Phase 2
       • Conjugation
         • Allows elimination
           • Add something basic to it
             • Has a positive charge
               • Can'tpass through membranes therefore has to be excreted in the urine
     • Paracetomal doesn't normally go into phase 1
       • If there is a build up then it can no longer be conjugated as there are insufficient conjugating enzymes
   • Determination of the half life through different equaitons
   • Determination of the constant through another equaition
   • As the concentration of the drug lowers its elimination lowers

3. Chromatin

   • Nucleosome
     • Histones
       • Four core histones
         • H2A
           • H2A and H2B dimers join to (H3:H4)2 from above and below
           • H2A variants
             • macro H2A
             • H2A.Z
             • H2A.X
             • H2A Bbd
         • H2B
         • H3
           • H3.1
             • H3.1 t
           • H3.2
           • H3.3
           • Cenap
         • H4
         • H2A and H2B form dimers
         • H3 and H4 form dimers
           • Then form tetramers
         • Dimerisation increases stability
       • Linker histone
         • H1
           • important in creating the 30nm solenoid
       • N terminal tails that can be modified covalently
       • Different histones alter the transcriptional ability of
     • DNA
     • 10 nm fibre
       • 30nm solenoid
         • 300nm solenoid
           • Coiled coil
             • Chromsomes
               • Transcriptionally silent
                 • As this is where DNA is replicated
               • Heterchromatin
                 • Constituitive
                   • Genes in this area are poorly expressed
                   • Centromeres and telomeres
                 • Facultative
                   • Genes in this area can become activated and expressed
               • Euchromatin
                 • Loosely packaged chromatin
                   • Contains genes that can be transcribed
               • Condensed 10,000 fold
             • 300nm solenoid coiled further using different scaffold proteins
             • Highly condensed
           • 30nm solenoid coiled further
             • Transcriptionally silent
             • Held in place by non-histone protiens
             • Proteins in place so that it can be unfolded to undergo replication
         • Nucleosome and linker DNA further coils
           • H1 linker histone sits in the middle of each turns
       • Nucleosome + linker DNA
         • Most open chromatin can be

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