(3) BIOCHEM fr and antioxidants

the primary free radicals (explain each)

• superoxide= Generated through incomplete reduction of oxygen in ETC or as a product of an enzymatic reactions.

• nitric oxide= Generated by a series of specific enzymes (NO synthase). reactive nitrogen species. best known for vasodilation.

what are free radicals produced by?

enzymes

can free radicals purposely produce?

yes

do molecules(FR) have the ability to leave cells and affect/impact on near by cells?

yes

how are free radicals formed?

•Generated through outside sources that damage or break bonds (like from smoking, radiation)

•incomplete oxidation reaction (electrons leak backwards, which generates superoxides)

•Enzymatic reactions

• normal metabolic process of the cell generate free radicals as part of the reaction

what does incomplete oxidation reaction mean?

electrons leak backwards, which generates superoxides

non-enzymatic sources of ROS (why FR formed);

•Environmental sources disrupt electrons in molecules in the body.

•Why oxygen

• present in high concentrations

• 2 unpaired electrons

•“Accidental” Generation

• Any reaction involving oxygen has the possibility of incomplete oxidation

endogenous production of ROS (why FR formed). what is it’s purpose?

→ often compartimentalized

→ enzymes in cell are producing them

why? because they are a signaling molecule

what is often compartimentalized?

endogenous (production of ROS)

what does ROS stand for?

reactive oxygen species

do most ROS have a short or long life span?

extremely short.

even though ROS have a extremely short life span, what can they do well?

they can cause substantial damage to tissue and cellular components

main ROS we talk about:

1. superoxide radical

2. hydrogen peroxide

3. hydroxyl radicals

what is superoxide primarily formed as?

•Primarily formed as an intermediate in biochemical reactions

explain superoxides

•Primarily formed as an intermediate in biochemical reactions

•Has a relatively long half life

•Main precursor of other ROS

•Can be converted to H2O2 (hydrogen peroxide) by a dismutation reaction

•Relatively low cytotoxicity

what ROS has a relatively long half life?

superoxide

what is the ROS that is the main precursor for other ROS?

superoxide

what ROS can be converted into H2O2 (hydrogen peroxide) by a dismutation reaction?

superoxide

what kind of reaction can superoxide be converted into H2O2 (hydrogen peroxide) by?

dismutation reaction

does superoxide have a relatively low or high cytotoxicity?

low

explain hydrogen peroxide

• Stable, permeable to membranes, and has a relatively long half life

• Does not directly oxidize DNA or Lipids, but may inactivate some enzymes

• Dangerous because it can generate hydroxyl radicals

• 

what ROS is not actually a free radical?

hydrogen peroxide

what ROS is stable and permeable to membranes?

hydrogen peroxide

what ROS has a relatively long half life?

hydrogen peroxide

what ROS does not directly oxidize DNA or lipids, but may inactivate some enzymnes?

hydrogen peroxide

what ROS is dangerous because it can generate hydroxyl radicals?

hydrogen peroxide

explain hydroxyl radicals

•Widely considered the most damaging ROS in cells

•Incredibly reactive

•Do damage close to their site of generation

what ROS is considered the most damaging ROS in cells?

hydroxyl radicals

what ROS has a short half life and is incredibly reactive?

hydroxyl radicals

what ROS damages close to their site of generation?

hydroxyl radicals

what are H-atom abstraction and chain reactions aka/mean?

aka steal electron/abstracting electron

most common consequence of H-atom abstraction and chain reactions is what? explain

• Most common consequence is lipid peroxidation

  • Membrane-bound proteins are damaged by propagation reactions (change reations)

    • Hydroxyl radicals remove a hydrogen atom from a PUFA creating a  lipid peroxyl radical

    • This reacts with another PUFA to form another lipid radical

    • Creates a chain reaction causing large amounts of damage to the cell

what can happen in H-atom abstraction and chain reactions;

• •Most common consequence is lipid peroxidation

• Decrease in membrane fluidity (=increased stiffness; cells no longer able to function properly)

• Increased “leakiness” of the membrane pores to substances which normally do not pass through the membrane

  • alter membrane; increase leak; more unwanted things in membrane

  • decrease membrane fluidity (cannot change shape relatively easy)

what does decreasing membrane fluidity do?

• increase stiffness

• decreases ability to change shape

explain the model of superoxide dismutase if radicals produced

superoxide dismutase

• Converts superoxide to hydrogen peroxide and oxygen

  • SOD1 – found in cytosol and mito

  • SOD2 – found in mito matrix

  • SOD3 – extracellular

explain the model of superoxide relating to glutathione peroxidase and catalase conversion

glutathione peroxidase and catalase

• Converts hydrogen peroxide to water and oxygen

  • GPx1 – cyt and mito

  • GPx2 – cyt

  • GPx3 – ec and cyt

  • GPx4 – mito and nuclei

  • GPx5 – ec and membrane

exogenous antioxidants are commonly associated with what? what are the examples?

→ Commonly associated with compounds found in your diet or in supplements

• vit E

• vit C

explain vit E

•fat soluble

•Protects against lipid peroxidation

explain vit C

•Water soluble

•Electron acceptor

•Reduces oxidized Vit E

fill in the blank:

vit ___recycles vit____

vit C recycles vit E

balancing free radical chart

(left side is reductive stress)