Alcohol metabolism 21

Question 1

Is ethanol water soluble or lipid soluble?

Answer 1

both

Question 2

Where is most ethanol metabolized

Answer 2

the liver

Question 3

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

Answer 3

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

Both produce NADH

Question 4

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

Answer 4

ADH1

liver

Question 5

Where is ADH4 found?

Answer 5

upper GI tract

Question 6

Where is ADH2 found?

Answer 6

liver and lower GI tract

Question 7

Where is ADH3 found and what is it active towards?

Answer 7

many tissues

inactive towards ethanol
active towards long chain alcohols

Question 8

What is the major ALDH ?

Answer 8

ALDH2 in the liver (mitochondrial)

Question 9

where in the cell is ALDH1 found?

Answer 9

cytoplasm

Question 10

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

Answer 10

flushing, nausea, vomiting, distaste for alcohol

-GLU to LYS at residue 487

Question 11

What does acetyl coA synthetase convert?

Answer 11

acetate –> acetyl coA

Question 12

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

Answer 12

ACS1 (cytosolic)

Question 13

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

Answer 13

ACSII

Question 14

What happens to the acetyl coA generated by ACS?

Answer 14

enters the TCA cycle and is oxidized to CO2

Question 15

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

Answer 15

MEOS in the liver - ER cytochrome P450s

Question 16

What are the two components of MEOS?

Answer 16

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

Question 17

Does ADH1 or CYP2E1 have a higher affinity for ethanol?

Answer 17

ADH1

cyp2E1 more involved with large quantities

Question 18

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

Answer 18

acetaldehyde and ROS

Question 19

Is CYP2E1 expression affected by alcohol consumption?

Answer 19

yes chronic consumption increases expression 5-10 fold

-ethanol stabilizes the protein

Question 20

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

Answer 20

1. genotype
2. drinking history
3. gender
4. quantity

Question 21

How are a heavy drinkers ADH and CYP2E1 levels affected?

Answer 21

ADH dec

CYP2E1 increases

Question 22

Women have less of what enzyme than men?

Answer 22

gastric ADH

Question 23

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

Answer 23

increased NADH/NAD+ ratio

Question 24

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

Answer 24

FA oxidation

TCA cycle

Question 25

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

Answer 25

acyl transferases

Question 26

What results from accumulation of VLDL in the liver?

Answer 26

fatty liver - hepatic steatosis | ethanol induced lipidemia

Question 27

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

Answer 27

ketone bodies

Question 28

Why are patients with gout advised not to drink?

Answer 28

increase of blood lactate decreases uric acid excretion in the kidney

Question 29

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

Answer 29

fasting state: hypoglycemia | with a meal: transient hyperglycemia

Question 30

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

Answer 30

acetylaldehyde adducts | ROS species

Question 31

Acetylaldehyde formation with AAs causes what?

Answer 31

decrease protein synthesis

Question 32

What antioxidant enzyme does acetyladehdye specifically adduct to?

Answer 32

GSH

Question 33

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

Answer 33

inhibits electron transport

Question 34

Adduct formation with tubulin affects what?

Answer 34

protein secretion

Question 35

accumulation of proteins causes what effect?

Answer 35

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

Question 36

What is fibrosis?

Answer 36

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

Question 37

What percentage of heavy drinkers progress from fibrosis to cirrhosis?

Answer 37

20%

Question 38

Is cirrhosis reversible?

Answer 38

nah dude you're screwed

Question 39

what causes jaundice?

Answer 39

diminished ability of the liver to conjugate and secrete bilirubin

Question 40

What are four alcohol related diseases?

Answer 40

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