Antioxidant Flashcards
1
Q
Diabetes the cost
A
- Ten years loss of life expectancy
- Last 10 years beset by complications
- CV, renal, ocular, neurological problem- microvasculature is seriously damaged
- All impact quality of life
2
Q
Standard advice to avoid this horror
A
- Maintain glucose levels between 4-7mM
- Do this for decades
- No backsliding
3
Q
What about antioxidants then
A
- The next slide shows the official advice given by the DOH on antioxidant usage in diabetes
4
Q
Why do diabetics suffer complications
A
- Diabetic tissues wear out faster than non-diabetic tissues
- Results in major cellular, tissue and organ failure
- Yes, I know that but what are the mechanisms behind it
5
Q
Normal cellular function
A
- All cells generate reactive species (radicals, superoxide, singlet oxygen, OH radicals) through normal function (mitochondria, P-450’s)
- All cells have evolved protective mechanisms to ensure these reactive species do not damage cells
- These systems include superoxide disumtase, catalase and the system
6
Q
Superoxide dismutase
A
- Converts superoxide to oxygen, can hydrogen peroxide in the process
- A copper/Zinc based version is cytoplasmic a managese version in mitochondial
- Found in all tissues
- Serveral variants
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7
Q
SOD1
A
- Mutations on SOD1 linked with ALS (Amyotrophic lateral sclerosis)
- Mutant SOD fails to remove superoxide which induces neuronal apoptosis
- Wild-type enzyme appears to maintain the solubility of mutant forms
- This causes the progression of ALS
8
Q
Catalase
A
- Catalase converts hydrogen peroxide from metabolic processes to oxygen and water
- Hydrogen peroxide is a problem chemical species as it can move through membranes
- Catalase is a haemoprotein found in the peroxisome
- Catalase also attenuates some toxins through peroxidation reactions
9
Q
Catalase: characteristics
A
- Expectionally stable tetramers, resistant to pH and protesases
- They are REDOX enzymes, their haem iron is oxidised by one molecule of hydrogen peroxid ; the oxyferryl species is reduced by another hydrogen peroxide forming water and oxygen and regenerating the enzyme
10
Q
Control of antioxidant systems
A
- GSH (Cysteine, glycine and glutamate)
- GSH is a thiol
- The oil in the engine
- Thiols repair and prevent change in structure so preserving function
- Thiol levels must not fall or oxidative damage outstrips repair
- Protective enzymes rely on GSH
11
Q
GSH
A
- GSH can quench reactive species itself
- GSH peroxidase/Transferase accelerate this process
- Cells must maintain >95% GSH as thiol
- GSSG is spent catridge
- GSH formed de novo and recycles as well
12
Q
GSH Synthesis
A
13
Q
GSH
A
- Has more than 30 known cellular functions
- Quenches cellular toxins GSH reacts and quenches, forming GS which reacts with another GS. forming GSSG
- Re-reduces spent antioxidants e.g. dehydroascorbate converted to ascorbate
- Maintains many anti-oxidants like a car alternator
14
Q
Oxidative stress
A
- Net imbalance between oxidants and their attenuation’s
- GSH maintained in levels proportionate to demand
- Liver? Erythrocyte?
- GSH circulation levels
- Shall we buy some
15
Q
Diabetes- net toxic effects
A
- Diabetes must deal with normal cellular oxidant attrition
- Diabetics exposed to high glucose levels
- Glucose forms toxic species AGE
- Defence mechanisms compromised
16
Q
Polyol pathway
A
- Cells sense high glucose
- They try to convert it to sorbitol by using aldose reductase
- This removes the glucose
- It uses reducing power, which could be used to propel antioxidant systems
