Tutorial: Alcohol metabolism Flashcards
How does the liver produce glucose during fasting?
Glycogen degradation
Gluconeogenesis
Use of glycogen
Fast
BUT depleted in 24 hours
only liver glycogen can be used to maintain blood glucose
What is gluconeogenesis?
Production of glucose from lactate, amino acids and glycerol
Only source of glucose during prolonged fasting
Where does gluconeogenesis occur?
Mostly in liver
Kidneys can also do it
What must gluconeogenesis do to produce glucose?
Bypass the three irreversible reactions of glycolysis
Hexokinase
Phosphofructokinase
Pyruvate kinase
Where is insulin released from?
Pancreatic beta cells
When is insulin secreted?
In response to increased blood glucose after carbohydrate rich meal
Action of insulin
Stimulates glucose consuming pathways
Inhibits glucose production
Lowers blood glucose
Channels excess nutrients into synthesis of glycogen, fat and protein
Where is glucagon released from?
Pancreatic alpha cells
When is glucagon secreted?
In response to hypoglycaemia
High in fasting state
Action of glucagon
Stimulates glucose producing pathways
Raises blood glucose levels
Prevents hypoglycaemia during fasting
When are Epinephrine (adrenaline) and Norepinephrine released?
Stress hormones
Released during physical exertion, cold exposure and emotional turmoil
Action of epinephrine and norepinephrine
In the liver, they favour gluconeogenesis over glycolysis
Provide fuel for muscles
Glucocorticoid function
Involved in metabolic aspects of circadian rhythm
Stimulate gluconeogenesis by inducing synthesis of gluconeogenic enzymes
Stimulates hepatic glycogenolysis
When are glucocorticoids released?
During sustained stress
Site of action of glucagon
Acts almost exclusively on liver
What is ethanol metabolized by?
Liver
Also in stomach, but to lesser extent
How is ethanol metabolized?
Ethanol is first oxidized to form acetaldehyde (alcohol dehydrogenase)
Acetaldehyde is oxidized to form acetate (aldehyde dehydrogenase)
Production of NADH
See figure
What happens to the acetate produced during alcohol metabolism in the liver and stomach?
Released into the blood and oxidized by other tissues
Kinetics of alcohol metbaolism
zero order (constant amount eliminated over time, independent of concentration)
What is Anatbuse?
Disulfiram
Inhibits mitochondrial acetaldehyde dehydrogenase
Used in treatment of alcohol abuse
What happens to other metabolic pathways when alcohol is consumed in large quantities?
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
Why is ethanol administered as a therapy for methanol poisoning?
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.
Biochemical and pathophysiological effects of methanol consumption?
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.
How should you treat a patient with methanol poisoning?
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
Why is alcohol consumption linked with unconsciousness?
Too much alcohol consumed too quickly. Body could not metabolize fast enough.
Alcohol depresses CNS. Hypoglycemia occurs, brain has no energy source. Gluconeogenesis inhibited.
How does alcohol inhibit gluconeogenesis?
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.
What is the difference between an acute condition of ethanol abuse and a chronic one?
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)
