Reactive oxygen species

Where are reactive oxygen species produced?

Mainly mitochondria

Lipoxygenases (LOX)

Cyclooxygenases (COX)

oxygen reduction chain into free radicals from the electron transport chain

Oxygen O2 +e-

superoxide radical O2• + e-

Superoxide dismultase (SOD)

Hydrogen peroxide H2O2 + e-

Catalase

Hydroxyl radical •OH + e-

Water H2O

What is a free radicals?

Unpaired e- → highly reactive

What other ways can •OH be produced and why are they bad?

• ionising radiation

• UV

• X rays/ gamma rays

Cause haemolytic in red blood cells + damage DNA

cannot be eliminated by an enzyme system

How does the body neutralise free radicals?

Antioxidants (endogenous and exogenous)

Name the endogenous antioxidants

Enzymatic : SOD, catalase, PRDX, GPX

Non-animatic: glutathione (water soluble) coenzyme Q10 (lipid soluble)

Small molecule: glutathione + PRDX

Large molecule: SOD, catalase, GPX

Exogenous antioxidants

• Vit C (peppers, strawberry, broccoli etc)

• Vit E (nuts, seed, veg oil)

• Carotenoids (carrot, tomato, spinach)

What is the structure of glutathione and how does it act as an antioxidant?

Gly-Cys-Glu

Thiol (SH) group donates an e- to R.O.S + reacts with another glutathione forming a disulphide bond with the enzyme glutathione peroxidase

How are R.O.S helpful?

• Phagocytes synthesise and store free radicals to use against pathogens

• Gene transcription

• Skin cell differentiation

• Induction of mutagenic response

What is oxidative stress?

Unbalance between the production and accumulation of R.O.S in cells and the ability of the body to detoxify it

What can oxidative stress lead to?

Lipid peroxidatjon → damage cell engraves

DNA damage → mutation

Protein modification

What happens in oxidative burst?

NADPH oxidase rapidly release superoxide and hydrogen peroxide from cells (usually leukocytes like neutrophils and monocytes)

Rapid release kills pathogens locally

How is chronic granulotamous disease caused?

Mutation → defective phagocyte NADPH oxidase → cannot do oxidative burst

** x- linked disorder

G6PDH deficiency

• x-linked

• Reduced production of NADPH

• Reduced ability to recycle oxidised glutathione back to reduced glutathione

• Form Heinz bodies

• Triggers: bacterial/ viral infections, antibiotics/anti-malaria, fava beans(broad beans)

How does an paracetamol (acetaminophen) cause death + what is a treatment option for its overdose?

Accumulation in NAPQI → uses up glutathione → oxidative stress

Treatment: acetylcysteine