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unit 6: MCP > Alcohol metabolism 21 > Flashcards

Alcohol metabolism 21 Flashcards

1
Q

Is ethanol water soluble or lipid soluble?

A

both

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2
Q

Where is most ethanol metabolized

A

the liver

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3
Q

What are the two steps of alcohol oxidation in the liver using ADH and ALDH?

A
  1. ADH in cytosol
    ethanol –> acetaldehyde
  2. ALDH in mitochondria
    acetaldehyde –> acetate

Both produce NADH

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4
Q

What is the highest affinity (lowest Km) ADH? where is it found?

A

ADH1

liver

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5
Q

Where is ADH4 found?

A

upper GI tract

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6
Q

Where is ADH2 found?

A

liver and lower GI tract

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7
Q

Where is ADH3 found and what is it active towards?

A

many tissues

inactive towards ethanol
active towards long chain alcohols

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8
Q

What is the major ALDH ?

A

ALDH2 in the liver (mitochondrial)

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9
Q

where in the cell is ALDH1 found?

A

cytoplasm

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10
Q

What are the symptoms of inactive ALDH2? what substitution causes this?

A

flushing, nausea, vomiting, distaste for alcohol

-GLU to LYS at residue 487

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11
Q

What does acetyl coA synthetase convert?

A

acetate –> acetyl coA

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12
Q

What is the primary isoform of acetyl coA synthetase in liver? What part of the cell is it found in?

A

ACS1 (cytosolic)

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13
Q

What acetyl coA synthetase isoform is in the mitochondria of heart and skeletal muscle?

A

ACSII

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14
Q

What happens to the acetyl coA generated by ACS?

A

enters the TCA cycle and is oxidized to CO2

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15
Q

What is a second pathway for the breakdown of ethanol besides ADH and ALDH?

A

MEOS in the liver - ER cytochrome P450s

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16
Q

What are the two components of MEOS?

A
  1. cytochrome P450 reductase
    - transfers e- via FAD and FMN from NADPH
  2. Cytochrome P450
    contains binding sites for O2 and ethanol
    carries out the reaction to acetaldehyde
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17
Q

Does ADH1 or CYP2E1 have a higher affinity for ethanol?

A

ADH1

cyp2E1 more involved with large quantities

18
Q

What products are produced by the oxidation of ethanol by CYP2E1?

A

acetaldehyde and ROS

19
Q

Is CYP2E1 expression affected by alcohol consumption?

A

yes chronic consumption increases expression 5-10 fold

-ethanol stabilizes the protein

20
Q

What are four types of variations that determine how well ethanol is metabolized in a person?

A
  1. genotype
  2. drinking history
  3. gender
  4. quantity
21
Q

How are a heavy drinkers ADH and CYP2E1 levels affected?

A

ADH dec

CYP2E1 increases

22
Q

Women have less of what enzyme than men?

A

gastric ADH

23
Q

Acute effects of alcohol damage are all a result of what?

A

increased NADH/NAD+ ratio

24
Q

What two metabolic processes does a high NADH/NAD+ ratio inhibit?

A

FA oxidation

TCA cycle

25
Q

What reesterifies fatty acids to G3P in the ER, due to a high NADH/NAD+ ratio?

A

acyl transferases

26
Q

What results from accumulation of VLDL in the liver?

A

fatty liver - hepatic steatosis

ethanol induced lipidemia

27
Q

Since TCA cycle is inhibited by NADH/NAD+, what are fatty acids converted to?

A

ketone bodies

28
Q

Why are patients with gout advised not to drink?

A

increase of blood lactate decreases uric acid excretion in the kidney

29
Q

alcohol in the fasting state can cause? alcohol with a meal causes?

A

fasting state: hypoglycemia

with a meal: transient hyperglycemia

30
Q

What specifically causes the chronic, irreversible effects of alcohol consumption?

A

acetylaldehyde adducts

ROS species

31
Q

Acetylaldehyde formation with AAs causes what?

A

decrease protein synthesis

32
Q

What antioxidant enzyme does acetyladehdye specifically adduct to?

A

GSH

33
Q

What is the effect of the peroxidation of lipids in the mitochondrial membrane?

A

inhibits electron transport

34
Q

Adduct formation with tubulin affects what?

A

protein secretion

35
Q

accumulation of proteins causes what effect?

A

water to enter hepatocytes
portal hypertension
cell damage - release of AST, ALT

36
Q

What is fibrosis?

A

a wound healing like reaction
overproduction of ECM
capillary formation in sinusoids

37
Q

What percentage of heavy drinkers progress from fibrosis to cirrhosis?

A

20%

38
Q

Is cirrhosis reversible?

A

nah dude you’re screwed

39
Q

what causes jaundice?

A

diminished ability of the liver to conjugate and secrete bilirubin

40
Q

What are four alcohol related diseases?

A
  1. obesity
  2. alcoholism
  3. jaundice
  4. liver fibrosis

unit 6: MCP (17 decks)

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