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L15 Reactive OXYGEN Species ROS = Free Radicals or = Will create…

- - - - Most formed in ETC after bumping into CoQH⚡
        *draw process from slide 4
    - - Hepatic CYP450 Reductase
        
        Phase I Drug metabolism in Liver
        Drug --[CYP450]---> Broken product
        
        O2⚡-
        escapes from active site of CYP450 Reductase
        
        :checkered_flag: Acetaminophen / Terbinafine can cause liver damage by producing lots of ROS during metabolism
- - - - 2 O2⚡- + 2H+
        
        O2 + H2O2
        
        2 NON-enzymatic ways to make OH⚡ from H2O2
        
        1. Haber-Weiss Rxn
        ( O2⚡- :heavy_plus_sign: H2O2)
        
        OH⚡ :heavy_plus_sign: O2 :heavy_plus_sign: H2O
        
        2. Fenton Rxn (Fe2+ :heavy_plus_sign: H2O2)
        
        OH⚡ :heavy_plus_sign: Fe3+ :heavy_plus_sign: OH-
        
        :checkered_flag: Iron chelating agents (e.g. dietary flavanoids) effective antioxidants b/c shield Fe away from H2O2
        
        H2O2 is converted to water! :potable_water:
        
        Radiolysis of Water (H2O) :potable_water:
        
        OH⚡ :heavy_plus_sign: H`
  - - - GSSG :heavy_plus_sign: NADPH :arrow_right: 2 :STAR:GSH :heavy_plus_sign: NADP+
    - - Very Important Antioxidant Enzyme in humans
        
        Pre-emtively destroys H2O2 and LOOH before joins Fenton Rxn
      - Requires a continuous supply of :STAR:GSH formed from: #
- - - - H2O
        
        :arrow_lower_right:
        
        More OH⚡
        (In cytoplasm, continuous)
    - - AH
        (protein)
        
        :arrow_left:
        
        A:zap:
        
        :arrow_left: Steals from BH
        *(BH = a different molecule)
        
        Continue Chain Rxn
  - - - Guanine is MISREAD as Thyamine
        
        :forbidden:Permanent DNA damage possible :forbidden:
- - - - Steal e- from neighboring PUFA (LH)
        
        Forms LOOH
        Lipid hydroperoxide
        :warning:similar to H2O2 reactivity:warning:
        
        :forbidden:FATTY FENTON RXN:forbidden:
        possible, which can also PROPAGATE to INITIATION
        
        :check:
        :explode:Glutathione Reductase:explode:**
        Versions of GR can reduce LOOH
        :check:
        
        Forming L-OH
        safe, will be excreted
        
        Forms L:zap:
        
        Will form Free Radical:zap:
        [PROPAGATION] #
      - Attack itself forming
        Cyclic Peroxide
        [TERMINATION]
        
        Forms Cyclic Endoperoxide
        
        Decomposes into MDA or Reactive Aldehydes
        
        MDA attached to DNA
        :forbidden:Highly Mutagenic!:forbidden:
        
        :!!: Patients with Breast or Lunch Cancer had :arrow_up::arrow_up: [MDA] in blood :!!:
        Unknown whether this is the cause or a consequence of cancer
- - - - Excess NO:zap:
        :heavy_plus_sign:
        O2:zap:-
        
        :explode:NO ENZYME:explode:
        
        :warning:Peroxynitrite (ONOO-):warning:
        (readily diffuses through cell membranes)
        
        Readily breaks down to OH:zap: