[MOD16A - BIOCHEM] Free Radicals and Oxygen Toxicity_2028

What is the primary gas-transporting molecule in the body?

Hemoglobin

A molecule in RBCs that transports oxygen and CO2 by binding to them via heme groups

Hemoglobin

What does each hemoglobin subunit contain that allows it to bind oxygen?

Heme group

What element in the heme group binds to oxygen?

Iron

What is cooperative binding in hemoglobin?

A process where binding of one oxygen molecule increases the affinity for subsequent oxygen molecules

[T/F] Hemoglobin binds oxygen more readily after the first O2 molecule binds.

TRUE

[T/F] Carbon dioxide binds to the same site on hemoglobin as oxygen.

FALSE. CO2 binds to different sites (amino termini), not the heme group.

What happens when carbon dioxide binds to hemoglobin?

It causes a conformational change that facilitates more CO2 binding and transport.

What does DPG stand for and how does it affect oxygen binding?

2,3-diphosphoglycerate; it decreases hemoglobin's affinity for oxygen.

Enumerate the two oxygen affinity states of hemoglobin and their DPG binding affinities.

Deoxyhemoglobin - high DPG affinity (8.5 × 10^4 M−1)

Oxyhemoglobin - low DPG affinity (300 M−1)

[T/F] DPG and oxygen compete for the same binding site on hemoglobin.

FALSE. They bind at different sites, but their effects are mutually exclusive.

A genetic disorder caused by structural mutations in hemoglobin leading to abnormal RBC shape

Sickle cell anemia

[T/F] Sickle cell anemia results from a mutation in the gene encoding hemoglobin.

TRUE

What causes sickling of red blood cells in sickle cell anemia?

Abnormal hemoglobin polymerization under low oxygen conditions

[T/F] Sickle cell anemia improves oxygen transport efficiency.

FALSE. It impairs oxygen delivery and causes vascular occlusion.

The process by which carbon dioxide affects hemoglobin's oxygen-binding affinity through pH changes

Bohr effect

The process where oxygenation of hemoglobin reduces its capacity to carry carbon dioxide

Haldane effect

What happens to oxygen transport when PCO2 increases in tissues?

Oxygen transport decreases (Bohr effect)

What happens to CO2 binding capacity when oxygen binds to hemoglobin?

It decreases (Haldane effect)

[T/F] The Bohr effect explains how O2 levels affect CO2 transport.

FALSE. The Bohr effect explains how CO2 and pH affect O2 binding.

[T/F] The Haldane effect helps remove CO2 in the lungs by increasing O2 binding.

TRUE

What is the clinical use of voxelotor?

It stabilizes hemoglobin in its high-affinity oxygen-binding state in sickle cell patients.

A drug that increases hemoglobin's oxygen affinity and reduces sickling

Voxelotor

[T/F] Voxelotor shifts the oxygen-hemoglobin dissociation curve to the right.

FALSE. It causes a left shift, indicating increased O2 affinity.

[T/F] Anemia can impair metabolism and cause hormonal and psychological changes.

TRUE

A condition resulting from an imbalance between free radical production and antioxidant defenses

Oxidative stress

What are reactive oxygen species (ROS)?

Molecules containing oxygen with unpaired electrons, making them highly reactive

[T/F] Oxidative stress occurs when antioxidants outnumber free radicals.

FALSE. Oxidative stress occurs when free radicals exceed antioxidant defenses.

What are the effects of excessive oxidative stress on biomolecules?

It damages DNA, proteins, lipids, and leads to mutations, cell death, or cancer.

[T/F] Oxidative stress plays a role in aging.

TRUE

What pro-inflammatory cytokines are upregulated by oxidative stress?

Interleukin-6 (IL-6)

Tumor necrosis factor-alpha (TNF-α)

[T/F] Oxidative stress suppresses immune response in inflammation.

FALSE. It activates immune pathways and exacerbates inflammation.

[T/F] Oxidative stress contributes to cancer development by damaging DNA.

TRUE

Unstable molecules with unpaired electrons that damage cells

Free radicals

Oxygen toxicity can occur through the excessive production of what type of molecules?

Reactive oxygen species (ROS)

A molecule that neutralizes free radicals by donating electrons or scavenging them

Antioxidant

What is the main function of antioxidants in the body?

To stabilize or neutralize free radicals and prevent oxidative damage

Maintaining balance between antioxidants and free radicals ensures

Cellular homeostasis

[T/F] Non-enzymatic antioxidants are mainly produced inside cells.

FALSE. They are primarily obtained from the diet.

How do free radicals contribute to the development of respiratory diseases?

By damaging lung tissues and promoting airway inflammation

What medical intervention may be used to supplement antioxidant defense?

Antioxidant supplements prescribed when necessary

What are the likely mechanisms behind lung cancer in chronic smokers and welders?

Accumulated free radical damage to lung cells

A 55-year-old man with poor diet and sun exposure presents with premature aging and inflammation. What could be elevated in labs?

Markers of oxidative stress

[T/F] Free radicals always cause cellular damage.

FALSE. Some free radicals have physiological roles in signaling and immunity.

A highly reactive molecule with an unpaired electron that contributes to oxidative damage

Free radical

How do free radicals promote atherosclerosis?

They oxidize lipids, contributing to plaque formation in blood vessels

What is the relationship between oxidative stress and aging?

Oxidative stress accumulates over time, impairing cellular structures and functions

How does oxidative stress contribute to joint inflammation?

By increasing the production of pro-inflammatory cytokines

[T/F] Free radicals are only formed by external pollutants.

FALSE. They are also produced during normal metabolism and immune responses.

What type of damage can ROS cause to DNA?

Mutations and strand breaks leading to cancer or apoptosis

What type of damage can ROS cause to proteins?

Denaturation, misfolding, and functional impairment

What type of damage can ROS cause to lipids?

Lipid peroxidation that disrupts cell membranes

A lifestyle modification that helps counter oxidative stress by increasing endogenous antioxidants

Regular physical exercise

Which diet component enhances the intake of non-enzymatic antioxidants?

Fruits, vegetables, and whole grains

[T/F] ROS are only harmful in the body.

FALSE. They have useful roles in cell signaling and immunity at controlled levels.

Why is it important for clinicians to understand oxidative stress in respiratory diseases?

To develop better treatment strategies and reduce long-term tissue damage

[T/F] Free radicals are byproducts of both normal and abnormal metabolic processes.

TRUE

A strategy used in critical care settings to prevent oxygen toxicity in patients receiving supplemental oxygen

Limiting oxygen concentration and exposure time

Enumerate the gases transported by hemoglobin.

Oxygen

Carbon dioxide

Carbon monoxide (in pathological conditions)

Enumerate the three forms in which carbon dioxide is transported in the blood.

Dissolved in plasma

Bound to hemoglobin

As bicarbonate ions

Enumerate the physiological factors that influence hemoglobin's oxygen-binding affinity.

pH

Temperature

CO2 concentration

Enumerate the two types of allosteric modulators of hemoglobin.

Homotropic (e.g. oxygen)

Heterotropic (e.g. protons, CO2, 2,3-BPG)

Enumerate possible causes of fatigue in anemia.

Reduced oxygen delivery to tissues

Impaired metabolism

Inflammation

Hormonal changes

Psychological factors

Enumerate oxidative stress-related neurodegenerative diseases.

Alzheimer's disease

Parkinson's disease

Amyotrophic lateral sclerosis

Huntington's disease

Enumerate oxidative stress-related cardiovascular diseases.

Atherosclerosis

Hypertension

Myocardial damage

Ischemia-reperfusion injury

Heart failure

Enumerate complications of diabetes related to oxidative stress.

Diabetic nephropathy

Diabetic retinopathy

Diabetic neuropathy

Diabetic cardiomyopathy

Enumerate inflammatory diseases linked to oxidative stress.

Rheumatoid arthritis

Inflammatory bowel disease

Asthma

Chronic obstructive pulmonary disease (COPD)

Enumerate internal (endogenous) sources of free radicals.

Normal metabolic processes

Inflammation

Immune responses

Enumerate external (exogenous) sources of free radicals.

Pollutants

Tobacco smoke

Certain drugs

Radiation

Enumerate examples of reactive oxygen species (ROS) involved in oxygen toxicity.

Superoxide anion

Hydrogen peroxide

Hydroxyl radical

What are two mechanisms by which oxygen toxicity damages cells?

1. Production of ROS leading to oxidative stress

2. Activation of inflammatory pathways causing tissue damage

Enumerate ways antioxidants counteract free radicals.

Donating electrons to stabilize free radicals

Scavenging free radicals directly

Enumerate common dietary antioxidants.

Vitamin C

Vitamin E

Beta-carotene

Selenium

Enumerate enzymatic antioxidants.

Superoxide dismutase (SOD)

Catalase

Glutathione peroxidase

Enumerate non-enzymatic antioxidants.

Vitamin C

Vitamin E

Beta-carotene

Polyphenols

Enumerate diseases commonly associated with increased free radical damage.

Cancer

Cardiovascular diseases

Neurodegenerative disorders

Diabetes

Inflammatory diseases

Enumerate respiratory diseases linked to oxidative stress.

Acute respiratory distress syndrome (ARDS)

Chronic obstructive pulmonary disease (COPD)

Asthma

Enumerate strategies to reduce free radical damage.

A balanced diet rich in antioxidants

Regular physical exercise

Stress management

Avoiding environmental pollutants

Limiting exposure to radiation and toxins

A 55-year-old smoker and welder develops lung cancer due to chronic free radical exposure. What are his risk factors?

Smoking (tobacco chemicals generate ROS)

Exposure to metal fumes

UV radiation from welding

Enumerate lifestyle factors that increase free radical production.

Smoking

Poor diet

Prolonged sun exposure

Exposure to environmental toxins

What body systems can be impaired by excessive oxidative stress?

Cardiovascular

Nervous

Immune

What are the body's natural defenses against oxidative stress?

Enzymatic antioxidants

Non-enzymatic antioxidants

Cellular repair systems

How can individuals reduce their risk of oxidative stress-related damage?

Lifestyle modification

Antioxidant-rich diet

Regular physical activity

Stress control

In oxidative stress, which cellular components are at highest risk of damage?

DNA

Proteins

Lipids