Oxidative stress & antioxidants Flashcards
Discuss other reactive oxygen species (ROS)
2O2.- + 2H+ –> H2O2 + O2 (SOD)
2H2O2 –> 2H2O + O2 (catalase)
Fe2+ + H2O2 –> Fe3+ + OH- + OH. (fenton reaction)
OH. + H+ + e- –> H2O
Discuss reactive nitrogen species (RNS)
NO. (nitric oxide) + O2.- (superoxide) –> ONOO- (peroxynitrate - NOT free radical)
Disuss OH.
most damaging & reactive - reacts with anything
Discuss O2.-
important source of ROS
damaging to DNA, protein & membrane
Discuss NO.
toxic at high level
signalling molecule:
vasodilation
neurotransmission
S-nitrosylation
Outline defences against ROS
SOD, catalase
antioxidants vit C & E
NADPH
glutathione (GSH)
How does glutathione protect cells from oxidative damage?
thiol (S-H) of Cys of glutathione donates e- to ROS using glutathione peroxidase
GSH now reacts with another GSH –> disulphide GSSG
How id GSSG reduced back to GSH?
GSSG reduced back to GSH using glutathione reductase using e- from NADPH (pentose phosphate pathway - formation of bases C5 & protect against free radicals)
How does antioxidants prevent cell from oxidative damage?
Vit E: lipid radical –> lipid (oxidised vit E)
Vit C: regenerates reduced form of vit E (by giving H atom to vit E)
non-enzymatic process
Explain the role of oxidative stress in disease & state examples
respiratory burst: rapid release of O2.- & H2O2 from phagocytic (WBC) cells e.g. neutrophils & monocytes to form ROS: HOCl.
rapid release of NO. with O2.- forms RNS: ONOO-
ROS & RNS destroy invading bacteria
Describe the production of superoxide radicals
some electrons from the ETC can escape & be taken up by free oxygens in the mitochondria forming free radicals
O2 + e- –> O2.- (superoxide radical)
What is galactose?
lack of galactokinase or uridyl transferase to break down galactose
What happens when galactokinase is deficient?
glucose + galactose –> galactitol (aldose reductase) NADPH –> NADP+ only as no other pathways to breakdown galactose
What does using the pathway involving aldose reductase cause?
NADPH to be used up - less protection against ROS - lens crystalline protein damaged through formation of disulphide bond –> cataract
osmotic pressure is also increased
What happens when there is a deficient of uridyl transferase?
galactose & galatose-1-P builds up (can’t form glucose-1-P)
galactose-1-P –> UDP-galactose (UDP-galactose epimerase)
a type of galactosaemia
What happens when there is a G6PDH deficiency?
G-6-P not converted to 6-phosphogluconate in pentose phosphate pathway and nucleotide can’t be biosynthesised
and NADP isn’t reduced to NADPH - leading to buildup of GSSG (can’t protect against ROS)
describe what happens in OD of paracetamol through the metabolism
metabolised in liver
paracetamol OD –> NAPQI (toxic metabolite) –> oxidative damage to liver cells (proteins, DNA, lipid peroxidation)
What is used to treat OD of paracetamol?
acetylcysteine treatment (boost glutathione levels) –> glutathione (GSH) - limit effects of NAPQI
Ischaemia reperfusion injury
reperfusion of oxygenated blood after ischaemia can cause MORE damage esp. mitochondria - products not completely metabolised can become ROS (sudden peak of nutrients etc.)
also loss of antioxidants during ischaemia
What are the consequences of reperfusion in ischaemia reperfusion injury?
high influx of Ca2+ in new blood - can cause Ca2+ overload esp. mitochondria (can cause cell death / release of fatty acid from Ca2+ soaps - affects membrane integrity - degrade)
What is a protective mechanism against ischaemia reperfusion injury from occuring again?
leukocytes to affected area leaves memory cells, so when ischaemia occurs again, body will know how to cope with it
