Redox Flashcards
What is redox biology
Concerns the flow of electrons between molecules
Gain of electrons= REduction
Loss of electrons= oxidation
OiL RiG
oxidation does not have to involve oxygen
The molecule that loses the electron (undergoes Oxidation) is the reducing agent
The molecule that gains the electron (undergoes reduction) is the oxidizing agent (oxygen is a good oxidant)
Photosynthesis and redox reaction
Redox rxns are the basis of all living processes
Photosynthesis is a redox reaction that removes electrons from water and passes them to carbon in CO2 doing 2 things:
1. carbon is reduced, forming polymers to build up plants
2. and oxidizing gas (O2) is generated and released into the environment
solar energy is thus captured and pushes the redox reaction to make CO2 (out of equilibrium) (life is kinetically stable but thermodynamically unstable)
H20 + CO2 –> O2 + reduced carbon
Redox energy gradient
Solar energy is captured in the redox gradient (o2 and reduced carbon chains are thermodynamically less stable than the h20 and CO2)
O2 is highly toxic and can destroy all reduced carbon compounds, the activation energy prevents oxygen from oxidizing the reduced carbon
Cell respiration takes the toxic o2 and allows it to be made in ATP
Oxygen is useful for introducing functional groups into molecules
a few metabolic enzymes use actual molecular O2. The pathways have evolved to tap directly into the redox gradient bc the ezymatic reaction uses molecular O2.
this makes an unsafe kinetic mechanis for the reduction of O2 in the redox gradient. The enzymes work to trap O2 with a metal ion (usually part of a heme). O2 gts reduced by NADPH electrons, and the reduced oxygen directly oxidizes reduced carbon polymers, but occasionally the reduced oxygen dissociates from the enzyme to for superoxide (o2-), H2O2, Oh- which are strong biological oxidants
leakage of electrons onto o2
The partial reduction of O2 is a leakage of electrons on oxygen outside of the safe environment of mito complex 4, its a metabolic short circuit that gives rise to radicals and oxidants
sequential reduction of o2 to h2o
Adding one electron to O2 makes a superoxide (O2-), a free radical but not a very reactive oxidant, that only has a few biological targets (Fe/S clusters and NO)
Adding an electron to superoxide tields H202, hydrogen peroxide. A strong oxidant found in bleach. It can directly oxidize some biological molecules that have metal ions.
Adding one electron to H2o2 yields hydroxyl radical, OH-, this is the strongest oxidant in biology and can oxidize pretty much all CC polymers, initiate chain reactions of oxidation, and cause DNA mutations. It is the central player in ionizing radiation induced cell death
adding an electron to OH- gives water
A free radical is an atom/molecule with an unpaired electron
Oxidative stress
oxidative stressors are kinetic mechanisms that tap into the redox energy source and override the activation energy, resulting in damaging intermediary oxidizers. Oxidative stress is where there are more oxidants than can be handeled by cell defense mechanisms
REdox recyclers are oxidative stressors, such as paraquat, take electrons from nadph destined for mito ATP production, and use them to reduce paraquat to a free cationic radical, the paraquat radical reduces O2 to o2-
Reactive oxygen species generation
Partially reduced forms of O2 and some of their oxidative products are termed the ROS. Enzymes are involved and they can attck biological molecules (PUFAs) to cause oxidative damage and potential cell death
NO can give rise to Reactive Nitrogen Species or RNS through oxidation, which are also damaging
RNS and ROS are able to interact to form other oxidative species, specifically NO can react with superoxide to form Peroxynitite, an oxidant highly active like the hydroxyl radical
protection mechanisms
Electrons that leak on to oxygen are part of aerobic respiration, and we have evolved a way to protect ourselves against ROS and RNS.
Enzymatic reactions mainly use GSH, but can also use peroxyredoxin using whole proteins, and recycling via thioredoxin, but still get the electrons from NADPH
Antioxidant protection involves Vitamin E (a tocopherol) and Vitamin C (ascorbate). Vitamin E is lipid soluble, C is water soluble and C helps with recycling E
Dietary antioxidants: usually little evidence that foods work invivo
How the free radical O2- (superoxide) can help
Superoxide is part of innate immunity: the respiratory burst or oxidative burst
Phagocytes (neutrophils, monocytes, and eosinophils) kill invading pathogens and defend the host through generation of animicrobial oxidants during a respiratory burst
superoxide is weakly microbicidal, but OH is strongly microbicidal
Phagocytes contain NADPH oxidase, which generates large amounts of superoxide that work in conjuction with MPO (myloperoxidase) to make HOCL
Chronic granulomatas disease (deficiency in NADPH oxidase)
NOX structure and function
NADPH oxidase (NOX) has several different enzymes with a catalytic subunit (NOX) and regulatory subunits in the membrane and cyto, and are involved in intracellular signaling
Damage of ROS formation
Reperfusion injury, Ishcemia (deprivation of O2) and regional ischemia occur in various situations:
Ischemia (myocardial infarction), Regional ischemia (stroke)
The paradox: once oxygen flow is regained, this causes reperfusion damage
(one reason is for xanthine), allopurinol (UW soln) inhibits xanthine in ischemic transplant tissue
Photo activation of oxygen
Oxygen ground state does not react with polymers bc its in triplet form, light can supply the energy ( or a photosensitizer like protoporphyrin) needed for singlet oxygen species
Singlet oxygen is a strong oxidant- porphyria is a defective heme synthesis- porphoryins accumulate in the skinacausing scin damage in the presence of sunlight and o2
photodynamic thearpies dies tumors and then localized light delivery
Nitric oxide
diatomic, lipophillic free radica in gas form, signaling molecules (gasotransmitters)- CO and h-sulfide)
nitro vasodilators
in the endothelium, contains a EDRF that allows for the vessels to dialate. Nitric oxide is an EDRF via guanylyl cyclase and cGMP
NO is derived from l-arginine
NOS structure
has a reductase that binds to NADPH and flavin co-factors, that passes electrons to an oxogynase. That contains a heme group and BH4 cofactor.
