Week 6 Flashcards
What can ROS also function as
Essential physiological regulators
What happens if ROS is high
Phagocytes has vital antimicrobial functions can also have deleterious effects on the host tissue injury and hyper-inflammatory response
What happens if ROS is low
NOX1 activated in epithelia cells affecting the cellular redox status and physiologically important cell proliferation differentation and motility
How is the redox regulation by ROS modulated
Specific reactive cysteine reisude within redox sensitive target protiens
What leads to the reversible modification of enzymatic activity
Oxidation of thiol groups SH of the cysteines
What is the first step of cysteine biochemistry
Formation of intra molecular and intermolecular disulfide bonds.
How are disulfide bonds formed
When two adjacent thiol groups are oxidized releasing proton and electron to form a covalent disulfide bond they can also be formed when reactive sulfenic acid interacts with nearby cysteines
What is the steps of oxidation of reactive thiol groups
Start with the thiol group move to the sulfenic form then fulfinic form and then finally sulfonic form which is not reversible
What is Glutahinoylation
A post translational protein modification it is a binding of glutathione tripeptide to a via the formation of a disulfide bond with a protien thiol
What can ROS regulate with critical singaling molecules
Cell proliferation, survival differenitation and metabolism
What do these critical signaling moelcules contain
Redox-reactive cysteine residues
What is there also potentinal for
DNA damage Iron homeostasis and Anti-oxidant and anti inflamatory repsonse
What is the key molecules of the redox regulation
Transcription factors Nrf2 and enzymes that control the thiol-disulfide exchange and levels of ROS (peroxiredoxin,thiroedoxin and sulfiredoxin)
What does Keap1 serve as and why
Oxidative stress sensor and it is a cysteine-rich protein and when modifications of thiol groups in this protein induce significant conformational changes and interactions with other proteins
What happens to Nrf2 in unstressed conditions
Nrf2 is associated with the Keap1 dimer and will undergo constans ubiquitination by Cul3 so Nrf2 is short lived
What hapens to Nrf2 under oxidative stress conditions
ROS will induce oxidation/chemical modifications of the cysteine reisudes which inactive Keap1 Nrf2 translocates to the nucleus and heterodimerizes with sMaf and now will bind to the antioxidant response elements that will now induce the expression of genes encoding antioxidant enzymes and cytoprotective protiens
What can Nrf2 do
Antioxiant enzymes are upregulation of genes encoding the enzymes that control thiol/disulfide and the intracellular leves of ROS
What are Peroxiredoxins
Reduce and inactivate hydrogen peroxide and organix peroxides and are small protiens and present in all biological kingsoms
What do Prxs usually contain
Two cysteine residues
What are the difference between the two cysteine residues
One is specifically oxidizes by hydrogen peroxide to cysteine sulfenic acid and this is called peroxidatic Cp the other cysteine is involved in the formation of a disulfide linkage with CP and is called the resolving Cys CR
Do all peroxiredoxins contain Cr
NO
What do Prxs function as
Homodimers arangend in a head to tail orientation from Cp and Cr cysteines
How many members are in the human family of perociredoxins
6
What are the three subfamiles of prx enzymes
Typical 2 cys
Atypical 2-cys
1-cys
