Oxidative Stress and Alcohol Metabolism

Question 1

Does alcohol have low or high energy content ?

Answer 1

High energy content , it has a higher energy content than protein and carbohydrates but lower energy content than fats. -29KJ/g

Question 2

Where is the majority of alcohol metabolised ?

Answer 2

Over 90% metabolised in the liver

Question 3

What is the recommended units a week of alcohol recommended ?

Answer 3

14 units a week spread over 3 days for BOTH MEN AND WOMEN.

Question 4

How many units of alcohol is in 8g of alcohol ?

Answer 4

One unit

Question 5

If someone heavily drinks one night , why are they recommended to not drive the following morning or afternoon ?

Answer 5

• because the elimination rate alcohol is 7g per hour so there is a danger that there still could be alcohol in the body above the recommended limit

Question 6

Outline the process of alcohol metabolism

Answer 6

ETHANOL IS CONVERTED INTO ACETALDEHYDE by alcohol dehydrogenase. This in turn converts NAD+ into NADH. 2. ACETALDEHYDE is then converted into acetate by aldehyde dehydrogenase. This in turn converts NAD+ into NADH. 3. Acetate is then conjugated to coenzyme A to form acetyl -coA which can then enter TCA cycle or utilised for fatty acid synthesis.

Question 7

What metabolite is responsible for the ‘hangover’ effect ?

Answer 7

ACETALDEHYDE

Question 8

Prolonged and excessive alcohol consumption can cause accumulation of ———- and a decrease in the ——- ratio

Answer 8

• accumulation of acetaldehyde - decreases in the NAD:NADH ratio

Question 9

How can a decrease in the NAD+/NADH ratio be responsible cause a change in liver metabolism ?

Answer 9

1) a decrease in the NAD+/NADH ratio results in less NAD+ for the conversion of lactate to Pyruvate which results in lactate accumulation in blood which results in lactic acidosis. Kidneys ability to excrete Uric acid reduced which results in urate crystals accumulating in tissues producing gout. 2) inadequate NAD+ for glycerol metabolism which results in deficit in gluconeogensis which results in hypoglycaemia 3) inadequate NAD+ for fatty acid oxidation which results in increased synthesis of triacylglycerols which results in fatty liver

Question 10

How can the increased acetyl-coA lead to fatty liver ?

Answer 10

• increased synthesis of fatty acids and ketone bodies which results in fatty liver

Question 11

What drug is used to treat chronic alcohol dependence ?

Answer 11

Disulfiram

Question 12

Explain how disulfiram works ?

Answer 12

It is an inhibitor of aldehyde dehydrogenase - once they drink alcohol , acetaldehyde will accumulate causing severe symptoms of hangover - patient associates drinking with being sick etc - classical conditioning

Question 13

Define a free radical

Answer 13

An atom or molecules that contains one or more unpaired electrons. - free radicals are very reactive and tend to acquire electrons from other atoms , molecules or ions

Question 14

What is oxidative stress

Answer 14

An imbalance between free radicals and antioxidants in your body

Question 15

What is reactive oxygen species an umbrella term for ?

Answer 15

• free radicals - reactive nitrogen species

Question 16

Is oxygen molecule a radical ?

Answer 16

Yes , it is a biracial it has two unpaired electrons in different orbitals

Question 17

What are reactive oxygen species ?

Answer 17

Chemically reactive spices that contain oxygen - these include superoxides , singlet oxygen , hydroxyl radical

Question 18

How is a superoxide formed ?

Answer 18

Produced by adding an electron to molecular oxygen - O2*-

Question 19

How is hydrogen peroxide formed ?

Answer 19

Adding an electron and 2H+ to a superoxide - hydrogen peroxide is NOT a free radical - but can react with Fe2+ to produce free radicals

Question 20

What is the most reactive and damaging free radical ?

Answer 20

Hydroxyl radical OH*

Question 21

How is hydroxyl radical made ?

Answer 21

Additional of electron and H+ to hydrogen peroxide

Question 22

What are reactive nitrogen species

Answer 22

A family of antimicrobial molecules derived from nitric oxide ( NO*) and superoxide (O2*-)

Question 23

Superoxide can react with nitric oxide to produce …

Answer 23

Peroxynitrite ( ONOO-) - its not itself a free radical but it is a powerful oxidant that can damage cells

Question 24

What are the two main types of reactive oxygen species damage of DNA?

Answer 24

1) ROS reacts with bases of D A which can lead to mispairing and mutation 2) ROS reacts with sugar of DNA which can cause strand break and mutation on repair

Question 25

when deoxyguanosine undergoes reactive oxygen species damage on the base , what molecule is produced ?

Answer 25

8-oxo-dEoxygyanosine

Question 26

What can 8-oxo-dG be a measurement for ?

Answer 26

As a measure the of oxidative damage

Question 27

How can ROS damage proteins?

Answer 27

1) reacts with the protein backbone which causes protein fragmentation which leads to degradation of protein 2) ROS reacts with the protein side gain which results in modified amino acids which can lead to disulfide bonds forming , hydroxylated addicts , dimers or carbonyls which leads to change in protein structure leading to a loss of function or gain in function.