S3) Alcohol Metabolism & Oxidative Stress Flashcards Preview

(LUSUMA) Metabolism, Endocrinology & Haematology > S3) Alcohol Metabolism & Oxidative Stress > Flashcards

Flashcards in S3) Alcohol Metabolism & Oxidative Stress Deck (49)
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Where does alcohol metabolism occur?

- >90% alcohol is metabolised by liver

- Remainder is excreted passively in urine and on breath


What are the recommended limits for alcohol consumption?

14 units/week spread over at least 3 days for both men & women 


Briefly describe the pathway involved in alcohol metabolism


What happens when acetaldehyde accumulates?

- Acetaldehyde is a toxic metabolite

- Accumulation causes a “Hangover” 


What happens to the acetate produced in alcohol metabolism?

- Acetate is conjugated to coenzyme A to form acetyl-CoA

- Acetyl-CoA is metabolised in TCA cycle / utilised for fatty acid synthesis 


How is acetaldehyde toxicity controlled?

Acetaldehyde toxicity normally kept to a minimum by aldehyde dehydrogenase (low Km for acetaldehyde) 


How does liver damage occur?

Prolonged and excessive alcohol consumption can cause sufficient acetaldehyde accumulation to cause liver damage 


Identify three forms of liver damage resulting from prolonged and excessive alcohol consumption

- “Fatty liver”

- Alcoholic hepatitis

- Alcoholic cirrhosis 


Indicate how liver damage can lead to changes in liver metabolism

- Excess NADH (decreased NAD:NADH)

- Excess Acetyl-CoA


What are the consequences of liver damage due to prolonged and excessive alcohol consumption?

- Lactic acidosis

- Fatty liver

- Hypoglycaemia

- Gout


Illustrate how excess NADH and Acetyl-CoA resulting from alcoholic liver damage can lead to the following consequences:

- Lactic acidosis

- Gout

- Hypoglycaemia

- Fatty liver


Which drug can be used to treat chronic alcohol dependence?



Explain how Disulfiram treats chronic alcohol dependence

- Disulfiram is an inhibitor of aldehyde dehydrogenase

- If patient drinks alcohol acetaldehyde will accumulate causing symptoms of a ‘hangover’ 


Cellular damage caused by ROS & RNS is a significant component in a wide range of disease states. 

Identify some


What is a free radical?

A free radical is an atom or molecule that contains 1/more unpaired electrons and is capable of independent existence e.g. OH


Why are free radicals so damaging?

- Free radicals are usually very reactive and tend to acquire electrons from other atoms, molecules or ions

- Reaction of a radical with a molecule typically generates a second radical thereby propagating damage


What are the two types of free radicals found in the body?

- Reactive Oxygen Species

- Reactive Nitrogen Species


Describe the pathway involved in the formation of reactive oxygen species


Explain how reactive nitrogen species are formed

O2•- + NO → ONOO

- Superoxide can react with nitric oxide to produce peroxynitrite

- Peroxynitrite is not a free radical, but is a powerful oxidant which damages cells 


Which three structures can ROS damage?


- Proteins

- Lipids


Outline the two ways in which ROS can damage DNA

ROS reacts with base – modified base can lead to mispairing and mutation

- ROS reacts with sugar (ribose or deoxyribose) – causing strand break and mutation


What are the possible consequences of ROS damage to DNA?


Outline, in detail, the two ways that ROS can damage proteins and the consequences of this


Disulphide bonds are formed between thiol groups of cysteine residues and play an important role in folding and stability of some proteins.

What happens when ROS interfere with these bonds?


Inappropriate disulphide bond formation can occur if ROS takes electrons from cysteines causing misfolding, crosslinking and disruption of function e.g. enzyme


Which process in triggered when ROS react with lipids?

Lipid peroxidation


In three steps, describe how lipid peroxidation occurs

⇒ Free radical extracts H+ from a polyunsaturated fatty acid in membrane lipid

⇒ Lipid radical forms & reacts with O2 to form a lipid peroxyl radical

⇒ Chain reaction formed as lipid peroxyl radical extracts hydrogen from nearby fatty acid


What are the consequences of lipid peroxidation?

Hydrophobic environment of bilayer disrupted and membrane integrity fails 


Identify three endogenous sources of biological oxidants

- Electron transport chain

- Nitric oxide synthases

- NADPH oxidases


Identify four exogenous sources of biological oxidants

- Radiation

- Pollutants

- Drugs

- Toxins


Explain how the ETC can be an endogenous source of ROS

- Electrons pass through ETC and reduce oxygen to form H2O at Complex IV

- Occasionally electrons can accidently escape chain and react with dissolved O2 to form superoxide