Lecture 3.1b - Alcohol metabolism and oxidative stress

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Questions and Answers

What is the primary site of reactive oxygen species production in the cell?

Nucleus

Lysosomes

Endoplasmic reticulum

Mitochondria (correct)

Which of the following enzymes is responsible for breaking down hydrogen peroxide to molecular oxygen and water?

Glutathione reductase

Lipoxygenase

Catalase (correct)

Superoxide dismutase

What is the primary function of antioxidants in the body?

To produce reactive oxygen species

To neutralize the excess of free radicals (correct)

To inhibit enzyme activity

To enhance oxidative stress

Which of the following reactive oxygen species is known for its ability to cause haemolysis in red blood cells?

Hydroxyl radicals Signup and view all the answers

What is the primary function of glutathione in the body?

To provide antioxidant defence Signup and view all the answers

Which of the following enzymes is responsible for converting superoxide radicals to hydrogen peroxide and oxygen?

Superoxide dismutase Signup and view all the answers

What is the source of hydroxyl radicals in the presence of ionising radiation?

Ionising radiation Signup and view all the answers

Which of the following reactive oxygen species is not typically eliminated by an enzyme system?

Hydroxyl radicals Signup and view all the answers

What is the primary mechanism by which the thiol group of Cys residue defends against ROS?

Donating an electron to ROS, forming a disulphide bond with another GSH Signup and view all the answers

What is the main difference between ROS in health and ROS in disease?

ROS in health are involved in cellular signalling, while ROS in disease are involved in oxidative stress Signup and view all the answers

What is the primary function of NADPH oxidase in the context of oxidative burst?

To rapidly release superoxide and hydrogen peroxide from cells Signup and view all the answers

What is the result of increased ROS production in cells and tissues?

Oxidative stress and potential damage to cellular structures Signup and view all the answers

What is the primary role of glutathione in antioxidant defence?

To donate an electron to ROS, forming a disulphide bond with another GSH Signup and view all the answers

What is the primary consequence of lipid peroxidation?

Damage to cell membrane Signup and view all the answers

What is the primary function of superoxide dismutase in antioxidant defence?

To convert superoxide into hydrogen peroxide Signup and view all the answers

What is the primary consequence of protein modification due to oxidative stress?

Modification of protein function, potentially leading to disease Signup and view all the answers

What is the primary function of phagocyte NADPH oxidase in the immune system?

To produce ROS to combat infection Signup and view all the answers

What is the role of G6PDH in maintaining the levels of glutathione in the cell?

It maintains the levels of NADPH, which is necessary for glutathione recycling Signup and view all the answers

What is the consequence of G6PDH deficiency in terms of glutathione levels?

Decreased levels of GSH and increased levels of GSSG Signup and view all the answers

What is the primary mechanism of acetaminophen toxicity?

Depletion of glutathione levels Signup and view all the answers

What is the role of glutathione in preventing NAPQI toxicity?

It scavenges ROS produced by NAPQI Signup and view all the answers

What is the consequence of chronic granulomatous disease in terms of immune defense?

Weakened immune response against pathogens Signup and view all the answers

What is the primary function of superoxide dismutase in the cell?

To scavenge superoxide radicals Signup and view all the answers

What is the role of catalase in the cell?

To scavenge hydrogen peroxide Signup and view all the answers

Study Notes

Reactive Oxygen Species (ROS)

ROS are metabolic by-products of oxygen metabolism, mainly produced in the mitochondria.
Other sources of ROS include lipoxygenases (LOX) and cyclooxygenases (COX).

Types of ROS

Superoxide radicals (O2*-), hydrogen peroxide (H2O2), hydroxyl radicals (*OH), and singlet oxygen (1O2), nitric oxide, and peroxynitrite.
Hydroxyl radicals can be produced by ionising radiation, are very damaging to cell membranes and DNA, and cannot be eliminated by an enzyme system.

Defense against ROS

The body has endogenous mechanisms to counteract ROS by producing antioxidants, which neutralize excess free radicals.
Endogenous antioxidants include superoxide dismutase (SOD), catalase, and glutathione (GSH).

Superoxide Dismutase/Catalase

SOD counters the damaging effects of superoxide by catalysing its conversion to hydrogen peroxide and oxygen.
Hydrogen peroxide is broken down to molecular oxygen and water by catalase.

Glutathione

Glutathione (GSH) is a tripeptide (Gly-Cys-Glu) that is synthesized by the body as an antioxidant to protect against oxidative damage.
The thiol group of the Cys residue donates an electron to ROS, reacting with another GSH to form a disulphide bond (GSSG) between the cysteine molecules.

Defense against ROS - Exogenous

Exogenous antioxidants are supplied through foods to counteract ROS.

ROS in Health

Under controlled levels, ROS can be a positive factor in health.
ROS are involved in various cellular signaling pathways, such as nitric oxide, and are also involved in spermatic function and fertilization.

ROS in Disease - Oxidative Stress

Oxidative stress is caused by an imbalance between ROS production and the body's ability to detoxify these reactive products.
When ROS production increases, it can lead to damage to important cellular structures like proteins, lipids, and nucleic acids, causing disease.

Conditions Associated with Oxidative Stress

Oxidative phosphorylation, radiation, lipid peroxidation, and DNA damage are all associated with oxidative stress.

Clinical Context

Oxidative burst is a rapid release of superoxide and hydrogen peroxide from cells, usually leukocytes, to kill pathogens.
Chronic granulomatous disease (CGD) is a genetic disorder that affects the immune system, leading to weak immune defense.
G6PDH deficiency is an X-linked disorder that affects the production of NADPH, leading to reduced ability to recycle oxidized glutathione.

Paracetamol (Acetaminophen)

Acetaminophen is widely used for its analgesic and antipyretic properties, but can be toxic in high doses.
Metabolism of acetaminophen leads to the formation of N-acetyl-p-benzo-quinone imine (NAPQI), which is toxic to hepatocytes.
Glutathione prevents NAPQI toxicity, and accumulation of NAPQI depletes glutathione, leading to oxidative stress.

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Description

Learn about the metabolism of ROS, their sources, and types, including superoxide radicals, hydrogen peroxide, and hydroxyl radicals.