Tutorial: Alcohol metabolism

Question 1

How does the liver produce glucose during fasting?

Answer 1

Glycogen degradation

Gluconeogenesis

Question 2

Use of glycogen

Answer 2

Fast

BUT depleted in 24 hours

only liver glycogen can be used to maintain blood glucose

Question 3

What is gluconeogenesis?

Answer 3

Production of glucose from lactate, amino acids and glycerol

Only source of glucose during prolonged fasting

Question 4

Where does gluconeogenesis occur?

Answer 4

Mostly in liver

Kidneys can also do it

Question 5

What must gluconeogenesis do to produce glucose?

Answer 5

Bypass the three irreversible reactions of glycolysis

Hexokinase

Phosphofructokinase

Pyruvate kinase

Question 6

Where is insulin released from?

Answer 6

Pancreatic beta cells

Question 7

When is insulin secreted?

Answer 7

In response to increased blood glucose after carbohydrate rich meal

Question 8

Action of insulin

Answer 8

Stimulates glucose consuming pathways

Inhibits glucose production

Lowers blood glucose

Channels excess nutrients into synthesis of glycogen, fat and protein

Question 9

Where is glucagon released from?

Answer 9

Pancreatic alpha cells

Question 10

When is glucagon secreted?

Answer 10

In response to hypoglycaemia

High in fasting state

Question 11

Action of glucagon

Answer 11

Stimulates glucose producing pathways

Raises blood glucose levels

Prevents hypoglycaemia during fasting

Question 12

When are Epinephrine (adrenaline) and Norepinephrine released?

Answer 12

Stress hormones

Released during physical exertion, cold exposure and emotional turmoil

Question 13

Action of epinephrine and norepinephrine

Answer 13

In the liver, they favour gluconeogenesis over glycolysis

Provide fuel for muscles

Question 14

Glucocorticoid function

Answer 14

Involved in metabolic aspects of circadian rhythm

Stimulate gluconeogenesis by inducing synthesis of gluconeogenic enzymes

Stimulates hepatic glycogenolysis

Question 15

When are glucocorticoids released?

Answer 15

During sustained stress

Question 16

Site of action of glucagon

Answer 16

Acts almost exclusively on liver

Question 17

What is ethanol metabolized by?

Answer 17

Liver

Also in stomach, but to lesser extent

Question 18

How is ethanol metabolized?

Answer 18

Ethanol is first oxidized to form acetaldehyde (alcohol dehydrogenase)

Acetaldehyde is oxidized to form acetate (aldehyde dehydrogenase)

Production of NADH

See figure

Question 19

What happens to the acetate produced during alcohol metabolism in the liver and stomach?

Answer 19

Released into the blood and oxidized by other tissues

Question 20

Kinetics of alcohol metbaolism

Answer 20

zero order (constant amount eliminated over time, independent of concentration)

Question 21

What is Anatbuse?

Answer 21

Disulfiram

Inhibits mitochondrial acetaldehyde dehydrogenase

Used in treatment of alcohol abuse

Question 22

What happens to other metabolic pathways when alcohol is consumed in large quantities?

Answer 22

Metabolism of ethanol produces large amounts of acetyl CoA, NADH and ATP

Depletion of NAD+ pushes pyruvate to lactate and oxaloacetate to malate, which impairs gluconeogenesis. Also, glycolysis pyruvate DH, TCA cycle and fatty acid oxidation are impaired

Fatty acids are turned into TGL and exported from liver as VLDL. Excess fat stays in liver.

Pyruvate and oxaloacetate are converted into malate and lactate

Question 23

Why is ethanol administered as a therapy for methanol poisoning?

Answer 23

Ethanol is a competitive inhibitor for alcohol dehydrogenase, as ADH has a greater affinity for ethanol than methanol or ethylene glycol .

This limits production of toxic metabolites. Ethanol is turned into ketones which can be metabolized, so it is less dangerous.

Question 24

Biochemical and pathophysiological effects of methanol consumption?

Answer 24

Production of formic acid = acidosis.

Formate causes retinal injury with optic disc hyperemia, edema, and eventually permanent blindness, as well as ischemic or hemorrhagic injury to the basal ganglia. These changes are postulated to result from disruption of mitochondrial function.

Question 25

How should you treat a patient with methanol poisoning?

Answer 25

Securing the patient’s airway, breathing, and circulation, and providing appropriate supportive care

Administeringsodium bicarbonate to correct systemic acidosis, which limits the penetration of toxic acids (eg, formic acid) into end-organ tissues such as the retina by converting them to the anion (eg, formate), which cannot diffuse across cell membrane

Inhibiting the enzyme alcohol dehydrogenase, with fomepizole

Performing hemodialysis for elevated toxic alcohol levels, severe acid-base derangements, or evidence of end-organ toxicity

Treating with cofactors (folic acid, thiamine, and pyridoxine) to optimize nontoxic metabolic pathways for the elimination of the parent alcohol or its metabolites

Question 26

Why is alcohol consumption linked with unconsciousness?

Answer 26

Too much alcohol consumed too quickly. Body could not metabolize fast enough.

Alcohol depresses CNS. Hypoglycemia occurs, brain has no energy source. Gluconeogenesis inhibited.

Question 27

How does alcohol inhibit gluconeogenesis?

Answer 27

Ethanol breakdown produces NADH, which pushes pyruvate to lactate and oxaloacetate to malate.

Depletes precursors for gluconeogenesis. If patient is not eating, no glucose available.

Question 28

What is the difference between an acute condition of ethanol abuse and a chronic one?

Answer 28

Acute: It’s reversible

Chronic: fatty liver disease, inflammation, liver apoptosis, cirrhosis. Increases risk of esophagus and oral cancers due to production of acetaldehyde and ROS. Increased tolerance to alcohol (induce enzymes that metabolize)