Lecture Notes: Reactive Oxygen Species (ROS) at Mga Kaugnay na Paksa

Ano ang ROS?

• ROS: Highly reactive molecules na may oxygen
• Forms: Free radicals at non-radicals
  • Free Radicals: Molekula na may unpaired electrons kaya sila reactive
  • Non-radicals: Molekula na hindi reactive sa una ngunit maaaring mag-generate ng radicals

Bakit Reactive si ROS?

• Free Radicals: May unpaired electrons sa outer shell kaya naghahanap ng electron para maging stable
• Non-radicals: Kahit hindi sila directly reactive, nagpo-produce pa rin sila ng free radicals

Kahalagahan ng ROS

• Natural na nagpo-produce ang cells ng small amounts ng ROS na natutulungan ng antioxidants
• Kapag may ionizing radiation, tumataas ang ROS levels at nagiging sanhi ng cellular damage
• Double-Edged Sword: Nagagamit din ito sa radiotherapy

Oxidation at Reduction

• Oxidation: Molekula ay naglo-lose ng electron; oxidizing agents ang nagiging sanhi nito
• Reduction: Molekula ay nagge-gain ng electron; reducing agents ang responsible dito
• Hydrogen: Losing hydrogen = oxidation; Gaining hydrogen = reduction
• Oxygen: Gaining oxygen = oxidation; Losing oxygen = reduction

Formation ng Superoxide sa Mitochondria

• Electron Transport Chain: Nag-ge-generate ng ROS sa mitochondria; oxygen ang final electron acceptor
• Superoxide Anion: Partial reduction ng oxygen nag-ge-generate nito

Radiolysis of Water

• Stage 1: Physical interaction ng ionizing radiation sa water molecules
• Stage 2: Physicochemical changes, kasama ang solvation ng free electrons
• Stage 3: Chemical stage kung saan nabubuo ang iba't ibang radicals gaya ng OH, H2O2

Molecular Mechanism of ROS Damage

DNA Damage

• 8-Oxoguanine Formation: Resulta ng hydroxyl radical attack sa guanine, sanhi ng mutation
• Cytosine Oxidation: Nagiging uracil, resulting in base conversion at C-to-T transition mutations
• Thymine Glycol Formation: Nagiging obstacle sa DNA replication
• AP Sites: Kapag na-remove ang base, nagiging sanhi ng mutations

Lipid Peroxidation

• PUFA Attack: ROS attacks the polyunsaturated fatty acids, leading to chain reactions
• Chain Reaction: Lipid radicals form, causing membrane dysfunction
• Toxic Byproducts: Production of aldehydes like MDA and HNE na nag-cause ng further damage

Protein Damage

• Protein Oxidation: Cystine at methionine oxidation leading to enzyme inactivation
• Protein Carboxylation: Leads to degradation by proteasome, causing loss of function

Biological Consequences

• DNA Mutations: Potential cause of cancer
• Membrane Dysfunction: Loss of cell integrity
• Enzyme Inactivation: Affects cellular functions
• Protein Aggregation: Linked to diseases like Alzheimer's and Parkinson's

Conclusion

• Understanding ROS and its impact is crucial sa pag-unawa ng cellular processes at potential therapeutic applications, kagaya ng radiotherapy at paggamit ng antioxidants.