Alcohol Metabolism

Question 1

4th major nutrient of body, why?

Answer 1

Ethanol; provides significant amount of energy (7kcal/g)

Question 2

1. Why is ethanol easily absorbed by small intestine
2. Where is ethanol broken down mostly
3. Ethanol is also lost through which organ

Answer 2

1. Both water and fat soluble
2. Liver
3. Lungs (think breathalyzer)

Question 3

Breakdown of ethanol involves what two enzymes

Answer 3

alchol and aldehyde dehydrogenase (ADH and ALDH) and cytochrome P450 enzymes (MEOS)

Question 4

Is ADH have high or low Km

Where is ADH located

Where is ALDH located

Answer 4

Low (so high affinity for ethanol)

Cytoplasm

Cytoplasm and mitochondria (but mostly mitochondria)

Question 5

ADH and ALDH breakdown ethanol into

Then when it enters blood it is transformed to

Answer 5

Acetate

Acetyl CoA

~so high energy state

Question 6

Usually no problems with ADH; what are problems common with ALDH

What is the effect

Answer 6

Can be polymorphic that will make the Km increase (decrease affinity - leading to accumulation of aldehyde)

Accumulation of aldehyde= hangover; common in East Asians

Question 7

When ADH converts ethanol to aldehyde what is released

Answer 7

NADH

~20% will use NADPH instead and will use MEOS enzyme

Question 8

How does cytochrome P450 act on substrate

Answer 8

Releases single oxygen atom which can form superoxides and other oxygen is used to form OH

Question 9

Which lipoprotein will rise the most ~10 hours of drinking alcohol

Answer 9

VLDL

~Because this process is happening in liver

Question 10

Signs of alcohol intoxication

How to treat it

Answer 10

Lactic acidemia and hypoglycemia

Glucose infusion

Question 11

Why does alcohol intoxication cause lactic acidemia

Answer 11

High NADH/NAD+ ratio will make pyruvate go to lactate; ADH releases NADH

Question 12

What is a drug used to help with chronic alcoholism

What does it do

Answer 12

Disulfiram

Competitive inhibitor of ALDH so every time they drink they will get a terrible hangover so they will no longer want to drink over time

Question 13

The fate of acetate (product of ethanol metabolism) is?

Answer 13

It is taken up by other tissues and activated to acetyl CoA

Question 14

The possibility of ROS being generated during ethanol metabolism occurs via which enzyme system

Answer 14

MEOS

Question 15

Why does alcohol intoxication cause hypoglycemia

Answer 15

Because synthesis of lactate limits gluconeogenesis from pyruvate (plus you usually do not eat when you are drunk-if you do happen to eat though, this will not happen)

Question 16

Why would a marathon runner die after drinking alcohol

Answer 16

Running increases anaerobic glycolysis leading to a lot of lactic acid; when drinking lactic acid will not be converted to pyruvate so it will accumulate and eventually lead to respiratory failure

Question 17

Ethanol effect on lipid metabolism

1. What inhibits fatty acid oxidation?
2. Why can acetyl CoA produced from ethanol not be used in TCA cycle?
3. What will this cause?
4. As a result, acetyl CoA will get forced into?

Answer 17

1. High NADH
2. Because of build up of NADH
3. Conversion of OAA back into malate to regenerate NAD+
4. Ketone synthesis; can possible lead to ketoacidosis

Question 18

Two main vitamin deficiencies in alcoholics and what does that cause?

Answer 18

Folate- megaloblastic anemia

Thiamine- Wernicke-Korsakoff syndrome

Question 19

Why can alcoholism cause a fatty liver?

Answer 19

Some fatty acids will be released into the bloodstream as VLDL (hyperlipidemia)

Question 20

How can alcoholism cause gout?

Answer 20

Causes a buildup of uric acid which leads to gout

Question 21

The enzyme that metabolize ethanol exists as a variety of isozymes. A slow activity of which enzyme is likely for an individual to exhibit very low tolerance to alcohol, leading to rarely drinking?

Answer 21

ALDH

Question 22

Irreversible stage of liver damage ?

Answer 22

Cirrhosis