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MEDI 202 - Genes To Community > Alcohol Metabolism > Flashcards

Alcohol Metabolism Flashcards

1
Q

What is ethanol used as?

A

Co-solvent to dissolve several insoluble drugs and serves as a mild sedative

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2
Q

What does ethanol bind to?

A

GABA and N-methyl-D-aspartic acid (NMDA) receptors and modulates their effects

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3
Q

What factors affect alcohol absorption?

A

Gastric emptying rate
Ethanol concentration
Drugs
Rate of consumption

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4
Q

How does gastric emptying rate affect alcohol absorption?

A

If empty stomach then gastric emptying rate increases, increased rate of alcohol absorption, while food (carbs, fats and proteins) does the opposite.

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5
Q

What is the first thing that occurs after ethanol is absorbed?

A

Enters portal vein and travels to the liver, first pass metabolism

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6
Q

Where is ethanol metabolized?

A

Stomach lining and mainly liver

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7
Q

What are the three main pathways for ethanol metabolism in hepatocytes?

A

Alcohol dehydrogenase, located at cytosol

Microsomal ethanol-oxidising system (MEOS), located at endoplasmic reticulum

Catalase pathway, located in peroxisomes

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8
Q

What do all alcohol metabolism pathways generate?

A

Acetaldehyde, a highly toxic metabolite

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9
Q

What are the effects of acetaldehyde?

A

Carcinogenic and Toxic effects

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10
Q

Explain the carcinogenic effects of acetaldehyde.

A

Associated with increased risk of mouth, throat, and oesophagus cancer.

Slowing down DNA replication

Inhibits DNA repair

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11
Q

Explain toxic effects of acetaldehyde.

A

Toxic to various organs: heart, lungs, nervous system
Disrupts normal cellular functions and contribute to tissue damage

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12
Q

What is the ADH pathway of alcohol metabolism?

A

Reversible step: Entail to Acetaldehyde (alcohol dehydrogenase)

Acetaldehyde to Acetate (aldehyde dehydrogenase)

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13
Q

Where do the different steps of the ADH pathway take place?

A

ADH in cytosol
ALSH in mitochondria

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14
Q

What happens to the acetate during the ADH pathway?

A

It turns into acetyl CoA, with the enzyme acetyl-CoA synthase

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15
Q

What kind of order does ethanol elimination follow?

A

Zero-order kinetics

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16
Q

What is zero-order kinetics?

A

The rate of metabolism is not dependent on the concentration of the substance

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17
Q

What happens to the substance during zero-order kinetics?

A

A constant amount of the substance is metabolised per unit of time.

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18
Q

How does alcohol dehydrogenase operate when saturated with ethanol?

A

Operates at a constant rate

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19
Q

What kind of enzyme is ADH?

A

NAD+-dependent cytoplasmic enzyme

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20
Q

What is the purpose of ADH?

A

To oxidize ethanol to acetaldehyde

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21
Q

How many isozymes of ADH are there?

A

6

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22
Q

What happens if ADH is mutated in some individuals?

A

Slower alcohol metabolism and even small volumes of alcohol may produce symptoms of intoxication

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23
Q

What kind of enzyme is ALDH?

A

A mitochondrial NAD+-dependent enzyme

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24
Q

What is the function of ALDH?

A

To oxidize acetaldehyde to acetate

25
Q

What is the role of ALDH?

A

Maintain low blood levels of acetaldehyde during alcohol oxidation

26
Q

What are the different classes of ADH isozymes?

A

Class I: ADH1A, ADH1B, ADH1C
Class II: ADH4
Class III: ADH3

27
Q

What does a lower Km value mean?

A

Higher affinity of enzyme for substrate

28
Q

Which are the two ALDH enzymes that metabolise acetaldehyde?

A

Cytosolic ALDH 1 and mitochondrial ALDH2

29
Q

What causes Asian flush syndrome?

A

A genetic mutation known as the ALDH2*2 allele resulting in a less active or non-functional form of the ALDH2 enzyme.

30
Q

What does the accumulation of toxic acetaldehyde lead to?

A

Increased heart rate, facial flushing, nausea, discomfort and headache.

31
Q

What is MEOS?

A

An alternative pathway for the metabolism of ethanol in the liver.

32
Q

What causes MEOS to become more active?

A

Chronic or heavy alcohol consumption

33
Q

Where is MEOS located?

A

In the endoplasmic reticulum of hepatocytes

34
Q

What is the primary enzyme responsible for the MEOS pathway?

A

Cytochrome P450 2E1

35
Q

What is the function of CYP2E1?

A

To metabolize ethanol into acetaldehyde

36
Q

What also occurs during the MEOS pathway?

A

Reactive oxygen species (ROS) and free radicals are produced as byproducts

37
Q

What do ROS and free fatty acids lead to?

A

Contribute to oxidative stress and damage to liver cells

38
Q

What is catalase?

A

An enzyme particularly in the peroxisomes

39
Q

What is the function of the catalase pathway?

A

Breakdown of hydrogen peroxide into water and oxygen

Catalyzes the conversion of ethanol directly to acetaldehyde and acetate

40
Q

What other enzymes have similar functions to catalase?

A

ADH and ALDH

41
Q

What is the minor role of of the catalase pathway?

A

Metabolizes ethanol in other tissues other than the liver

42
Q

Which enzyme (s) are the most responsible for the metabolism of ethanol?

A

ADH and ALDH

43
Q

How is ethanol non-oxidatively metabolised?

A

Fatty acid ethyl ester synthase
Phospholipase D

44
Q

What molecules are produced when the reaction is catalysed by FAEE synthase?

A

Fatty acid ethyl esters which then leads to tissue injury

45
Q

What is formed when a reaction is catalysed by PLD?

A

Phospholipid known as phosphatidyl ethanol which interferes with PLD-dependent signalling

46
Q

What are the consequences of biomedical pathways triggered by alcohol metabolism? And why do they occur?

A

They occur because there is an increase in NADH and Acetyl CoA and a decrease in NAD+ to NADH

Consequences:
- Glycolysis dysregulation
- LActic acidosis
- Inhibition of gluconeogenesis and hypoglycemia
- Dysregulation of TCA cycle
- Effect on fatty acid synthesis and oxidation

47
Q

What causes the dysregulation of glycolysis?

A

Increase levels of NADH after GADP is converted to 1,3-bisphosphoglycerate

48
Q

What causes lactic acidosis?

A

Increase in NADH after pyruvate is converted into lactate

49
Q

What causes the inhibition of gluconeogenesis and hypoglycemia?

A

Deficiency of pyruvate –> inadequate formation of oxaloacetate

That results in suppression of gluconeogenesis which leads to hypoglycaemia

50
Q

Why is there an effect on the TCA cycle?

A

Affected at the level of malate dehydrogenase because there is an increase of NADH in mitochondria which will shift the reaction backwards leading to increase of malate

51
Q

What is the effect on the TCA cycle?

A

It is suppressed

52
Q

What is the effect on fatty acid synthesis?

A

Fatty acid synthesis increases and so does oxidation

53
Q

Why is there an increase in fatty acid synthesis?

A

Increase in acetyl CoA which causes an increase in malonyl CoA and thus increase in fatty acid synthesis.

54
Q

What causes fatty liver disease?

A

Increase in malonyl CoA which inhibits fatty acid catabolism and thus there is triglyceride accumulation which leads to hepatosteasis

55
Q

What is cirrhosis?

A

Long-term damage characterized by replacement of normal liver tissue with scar tissues

56
Q

What leads to liver damage?

A

Accumulation of excess fat in the liver due to increased synthesis of fat

57
Q

What happens if there is liver damage?

A

Enlarge adipose cells choke off nutrient and O2 supply to the liver cells

Engorged adipose cells burst and die

Scar tisse

58
Q

What are some causes of cirrhosis?

A

Chronic alcohol abuse
Chronic viral hepatitis
Fat accumulation in the liver
Iron buildup
Cystic fibrosis
Destruction of bile ducts
Hardening and scarring of bile ducts

MEDI 202 - Genes To Community (23 decks)

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