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Flashcards in Ethanol Metabolism Deck (75):
1

What is the 4th major nutrient that provides a significant amount of energy in many people?

Ethanol

2

How many kcal/g in alcohol?

7

3

Calories of alcohol

A lot of calories, although they are empty calories because they have no nutritional value

4

How many grams of alcohol does the "standard drink" have?

14 grams

5

What is the estimated calories in a drink (minus the mixers used)

98

6

What is the 3rd leading preventable cause of death?

Alcoholism

7

What percentage of men meet the criteria for alcoholism?

17%

8

What percentage of women meet the criteria for alcoholism?

8%

9

Affects of over drinking on brain?

Interferes with the brain's communication pathways

10

Affect of drinking on heart

Can damage the heart leading to cardiomyopathy, arrhythmias, stoke, high blood pressure

11

Drinking affects on liver

Steatosis, alcoholic hepatitis, fibrosis, cirrhosis

12

What is the 1st severely damaged organ from drinking?

Liver

13

Affects of drinking on pancreas

Produces toxic substances that can lead to pancreatitis

14

Affects of drinking on eyes

Short and long term vision problems

15

What is over consumption of alcohol a risk factor for?

Many cancers

16

What does over consumption of alcohol interfere with?

Proper function of the immune system therefore decrease the body's ability to fight infections

17

Solubility of ethanol

Both water and fat soluble

18

Absorption of alcohol into the intestine

Very easily absorbed by the intestine and readily enters the blood stream because of the fat and water soluble characteristics of ethanol

19

Where can a small amount of ethanol be metabolized?

By cells in the upper GI tract

20

What happen to a small amount of ethanol?

Lost through the lungs and kidneys

21

Where is the majority of ethanol processed?

In the liver via 2 pathways

22

What are the two pathways that liver can process ethanol?

1. Involves alcohol dehydrogenase (ADH)
2. Uses the microsomal ethanol oxidizing systems (MEOS) relying on cytochrome P450 enzymes

23

What do we even have enzymes to process alcohol?

Intestinal bacteria will produce ethanol via fermentation, that's why we have the enzyme to break it down

24

Where does ethanol metabolism predominantly happen?

Liver

25

Ethanol metabolism via MEOS

10-20%
Extremely upregulated

26

Ethanol metabolism via ADH system

-80-90%
-uses ADH and ALDH

27

What is the damaging molecule of excessive drinking?

Acetaldehyde H3C-CHO

28

What does ADH do to ethanol?

Converts it to acetaldehyde

29

What is the rate limiting step in ethanol metabolism?

ADH and the availability of NAD+

30

What is another limiting factor for alcohol metabolism other than ADH?

Availability of NAD+

31

What is the Km of ADH for ethanol?

Near 1 mmol/L

32

When does the enzyme get saturated when drinking alcohol?

ADH gets saturated essentially after one drink, and alcohol metabolism follows zero order kinetics

33

What kind of kinetics does alcohol metabolism follow?

Zero order kinetics

34

What happens when ADH is saturated?

Additional ethanol circulates in blood until active site opens up

35

How much alcohol does a person metabolize per hour?

About 10g of alcohol per hour

36

How does the blood alcohol level decrease per hour?

By about 0.15g/L every hour. Important calculations after car accidents

37

ALDH in east asians

Atypical with a single amino acid substitution
Glu---Lys

38

Dominant negative mutation of ALDH

-Single amino acid mutation of ALDH of glu---lys
--even heterozygotes, who still produce the normal enzyme in addition to the defective one, have near zero enzyme activity

39

What happens to someone with atypical ALDH when they drink?

The toxic acetaldehyde accumulates to high levels after only one or two drinks

40

Oriental flush response

-asians typically have atypical ALDH
-causes vasodilation, facial flushing, tachycardia

41

Rate of alcoholism in asians

Barely any. Oriental flush response is so unpleasant that no one wants to drink

42

What percentage of asians have atypical ADH?

30-40%

43

What is one symptom of acetaldehyde toxicity?

Flushing of the face and nausea

44

This inhibits aldehyde dehydrogenase, which will result in the accumulation of acetaldehyde after ingestion of alcohol.

Disulfiram

45

What is disulfiram used for?

As a deterrent from drinking from the sickness that will result

46

What happens if a person is on disulfiram and still drinks?

The damage caused by acetaldehyde that is seen in long time alcoholics will be accelerated

47

What is another compound that will have a more immediate affect on ethanol metabolism?

NADH

48

What does the processing of alcohol in the liver produce?

Large quantities of NADH in the liver

49

Drinking only a moderate amount of alcohol and NADH in liver

Likely that it will not result in significant changes (unless fasting)

50

Large amount of NADH building up

Alter many metabolic processes

51

When are significant effects of NADH build up seen?

Found mainly in heavy drinkers, or occasional drinkers that binge

52

Large build up of NADH in well fed state

When the liver is taking up glucose and performing glycolysis producing NADH and pyruvate, high levels of NADH will inhibit PDH complex and cause pyruvate to be converted into lactate resulting in lactic acidosis

53

Secondary effect of lactic acidosis

Will be the underexcretion of uric acid, resulting in hyperurecima

54

Build up of large amounts of NADH in fasting state

Liver will try to perform gluconeogensis
HOWEVER
-precursors will be diverted at pyruvate to the production of lactate
-if liver glycogen stores depleted, this can result in hypolycemia

55

Hypoglycemic effect of fasting and drinking

Can happen to even occasional drinkers, if they happen to drink when their glycogen stores are depleted

56

Is alcohol a substrate for gluconeogensis?

Nom it is ketogenic but not glucogenic

57

What do high levels of NADH inhibit?

Oxidation of fatty acids

58

Net result of inhibition of oxidation of fatty acids due to high levels of NADH

Accumulation of TAG as lipid droplets leading to fatty liver disease, some of the fat is released into the blood stream as VLDLs, which causes hyperlipidemia

59

The acetyl CoA that is produced from acetate that results from ethanol breakdown

Can not be used in the TCA cycle because of the build up of NADHq

60

High ratio of acetyl CoA and NADH

Causes the conversion of oxaloacetate back into malate to regenerate NAD+, but since there is already too much fat, that pathway will be inhibited too

61

What happens to acetyl CoA in ethanol consumption

Tends to get forced into the pathway for ketone syntheiss and ketoacidosis can result

62

Ethanol effects on nitrogen metabolism

Hyperammonemia and hyperbilirubinemia will result from liver failure

63

Cytochrome P450 in ethanol metabolism

The induction of cytochrome P450 enzymes and their increased role in ethanol metabolism results in a side effect of free radical production

64

Acetaldehyde and free radicals

It is a reactive compound that can bind glutathione, depleting glutathione supplies and reducing the cells ability to neutralize free radicals

65

Free radical mediated damage to the liver

Results in cirrhosis and eventually destruction of the liver

66

Why do alcoholics suffer from malnutrition?

-alcohol will provide significant calories while providing very little (or no) other nutrients
-the negative effects on the liver, pancreas, and GI tract further increase nutritional deficiencies

67

What are the two vitamin deficiencies prevalent in alcoholics

-folate deficiency
-thiamine deficiency

68

Folate deficiency in alcoholics

Results in megaloblastic anemia

69

Thiamine deficiency in alcoholics

Due to alcohol abuse and causes Wenicke-Korsakoff syndrome divided into two conditions

70

Wernickes encephalopathy

Reversible early stage of thiamine deficiency

71

Karsakoff syndrome

Thiamine deficiency
-end stage, brain damage and death

72

FASD

Any physical or developmental disorders causes by prenatal alcohol exposure

73

When is the time frame that the most vital organs can be especially damaged in babies?

First 3 months of pregnancy

74

Alcohol metabolism of pregnant women

Much more depressed compared with that of a non pregnant woman, as estrogen largely inhibit the activity of ADH

75

What hormone largely inhibits the activity of ADH?

Estrogen