L3 Ethanol Metabolism

The initial stage of liver damage, characterized by liver enlargement, fat accumulation, collagen fiber formation (fibrosis), and regeneration of liver cells (hepatocytes) forming nodules.

A serious liver disease that results from chronic liver damage, marked by scarring (fibrosis), loss of normal liver function, and shrinkage of the liver.

The process of converting ammonia into urea, which is a less toxic form that can be excreted by the kidneys.

The breakdown of heme, a component of hemoglobin, which results in the production of bilirubin, a yellow pigment.

A condition characterized by yellowing of the skin and whites of the eyes due to an accumulation of bilirubin, a product of heme degradation.

A type of alcohol poisoning caused by the accumulation of formic acid in the body.

The breakdown of methanol, a type of alcohol, into formaldehyde and then formic acid.

A highly toxic chemical produced during methanol metabolism, responsible for the adverse effects of methanol poisoning.

The liver is the primary organ responsible for ethanol breakdown. This happens primarily through two pathways: Alcohol Dehydrogenase (ADH) and Microsomal Ethanol Oxidizing System (MEOS).

Alcohol dehydrogenase (ADH) is an enzyme in the cytoplasm of liver cells. It converts ethanol to acetaldehyde, a toxic byproduct.

Acetaldehyde dehydrogenase (ALDH) is another enzyme, located in the mitochondria. It converts acetaldehyde to acetate, a less toxic form.

Acetaldehyde, a product of ADH, is toxic. It can cause a range of effects, including flushing, nausea, and headaches. Acetate, the product of ALDH, is less toxic and can be further metabolized.

Acetate is taken up by muscles to be converted to acetyl CoA. This acetyl CoA fuels the citric acid cycle (Krebs cycle), which generates energy in the form of ATP.

Ethanol metabolism generates energy, unlike other substances that are stored in the body. Each gram of ethanol yields 7 kcal of energy.

A small percentage of ethanol is excreted through the kidneys and lungs. The majority of ethanol is metabolized by the liver.

Genetic variations in Alcohol Dehydrogenase (ADH) and Acetaldehyde Dehydrogenase (ALDH) genes can influence the risk of developing alcoholism.

Different versions of the ADH1B and ADH1C genes encode highly active ADH enzymes, leading to faster breakdown of alcohol. This faster breakdown helps protect against alcoholism.

Acetaldehyde Dehydrogenase (ALDH) is a crucial enzyme responsible for metabolizing acetaldehyde, a toxic byproduct of alcohol breakdown.

A common variant of the ALDH2 gene (ALDH2*2) significantly reduces the enzyme's effectiveness, leading to acetaldehyde buildup and increased risk of alcoholism.

Homozygosity for the ALDH2*2 allele provides complete protection against alcoholism due to extremely inefficient acetaldehyde metabolism.

Disulfiram, a drug used to deter alcohol consumption, functions by inhibiting ALDH, causing acetaldehyde buildup and unpleasant reactions. This deters individuals from drinking.

The Microsomal Ethanol Oxidizing System (MEOS) plays a minor role in alcohol metabolism, particularly at high alcohol concentrations.

Chronic alcohol consumption induces the activity of CYP2E1, a key enzyme in the MEOS system. This can lead to faster alcohol breakdown but also causes acetaldehyde accumulation, potentially leading to liver damage.

The process of ethanol metabolism can lead to an increase in the ratio of NADH to NAD+ in the liver. This shift in the ratio inhibits fatty acid oxidation and the TCA cycle, resulting in the accumulation of fatty acids.

When fatty acid oxidation is inhibited due to the increased NADH/NAD+ ratio, the liver starts to accumulate fatty acids. These fatty acids are then repackaged into triglycerides, leading to the development of fatty liver.

Ethanol metabolism leads to a high NADH/NAD+ ratio, shifting the equilibrium of oxaloacetate (OAA) towards malate. This shift diverts acetyl-CoA away from the TCA cycle and towards ketogenesis.

The increased production of ketone bodies in the liver is exacerbated by the fact that muscle cells prefer to utilize acetate, derived from ethanol metabolism, as fuel. This reduces the muscle's capacity to oxidize ketone bodies, leading to even higher blood ketone levels.

Chronic ethanol abuse disrupts the delicate balance of liver metabolism, leading to a series of events that culminate in liver damage. This damage manifests as fatty liver, hepatitis, and cirrhosis.

The accumulation of acetaldehyde, a byproduct of ethanol metabolism, is responsible for the nausea and vomiting experienced during acute alcohol intoxication.

Ethanol metabolism can trigger both hypoglycemia and hyperglycemia depending on various factors like dietary state and the individual's overall health.

Cytochrome P450 enzymes, involved in ethanol metabolism, can produce free radicals. These free radicals contribute to oxidative stress and can exacerbate liver injury, potentially leading to cirrhosis.

Ethanol metabolism leads to a buildup of NADH, which inhibits gluconeogenesis by decreasing the availability of key precursors like oxaloacetate and glycerol. This can lead to hypoglycemia.

The buildup of NADH in the liver due to ethanol metabolism promotes the conversion of pyruvate to lactate. This lactate can't be used for gluconeogenesis and can contribute to hypoglycemia.

The high NADH/NAD+ ratio caused by ethanol metabolism can temporarily increase blood sugar levels. This is because the excess NADH inhibits glycolysis, preventing the breakdown of glucose.

Acetaldehyde, a toxic byproduct of ethanol metabolism, can bind to various molecules in the liver, including amino acids, sulfhydryl groups, nucleotides, and phospholipids, forming adducts. This can disrupt normal liver function.

Chronic ethanol abuse can lead to fatty liver, hepatitis, and cirrhosis. Acetaldehyde and free radicals generated from ethanol metabolism contribute to these conditions.

Chronic ethanol abuse can disrupt protein synthesis in the liver due to the binding of acetaldehyde to amino acids. This can impair the production and secretion of essential plasma proteins.

Ethanol metabolism increases the production of reactive oxygen species (free radicals) in the liver, which can damage mitochondria and disrupt the electron transport chain. This can further impair acetaldehyde oxidation and overall liver function.

Impaired VLDL secretion from the liver due to damage to microtubules can lead to an accumulation of VLDL in the liver, contributing to the development of fatty liver.

Ethanol metabolism primarily occurs in the liver using two enzymes: alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS).

Alcohol dehydrogenase (ADH) is a cytoplasmic enzyme that converts ethanol to acetaldehyde, a toxic byproduct, using NAD+ as a cofactor.

Acetaldehyde dehydrogenase (ALDH) is a mitochondrial enzyme responsible for converting acetaldehyde to acetate, a less toxic form, using NAD+ as a cofactor.

Ethanol metabolism yields 7 kcal of energy per gram, unlike many other substances stored in the body.

Most acetate enters the bloodstream, is taken up by skeletal muscle, and converted to acetyl CoA, entering the TCA cycle for energy production.

Genetic variations in ADH and ALDH genes can influence the metabolism of ethanol, contributing to factors like alcohol tolerance and potential risk of alcoholism.

The microsomal ethanol oxidizing system (MEOS) is a minor pathway for ethanol metabolism, becoming more active at higher alcohol concentrations.

Chronic ethanol consumption induces CYP2E1, an enzyme in the MEOS system, leading to faster ethanol breakdown but also increasing the production of toxic byproducts, potentially contributing to liver damage.

The buildup of formic acid from methanol metabolism can disrupt mitochondrial function, leading to vision loss due to damage in the optic nerve.

Cytochrome P450 enzymes, involved in ethanol metabolism, can generate free radicals, which contribute to oxidative stress and can exacerbate liver injury, potentially leading to cirrhosis.

Ethanol metabolism generates a high NADH/NAD+ ratio in the liver, which inhibits fatty acid oxidation and the TCA cycle, leading to the accumulation of fatty acids.

A high NADH/NAD+ ratio in the liver favors the formation of glycerol-3-phosphate, which is used for triglyceride synthesis, leading to fatty liver.

Acetaldehyde dehydrogenase (ALDH) is responsible for converting acetaldehyde, a toxic byproduct of ethanol metabolism, into acetate, a less toxic form.

Ethanol metabolism can disrupt the delicate balance of liver metabolism, leading to a series of events that culminate in liver damage, manifested as fatty liver, hepatitis, and cirrhosis.

The accumulation of acetaldehyde, a byproduct of ethanol metabolism, is responsible for the nausea and vomiting experienced during acute alcohol intoxication.

Ethanol metabolism can lead to both hypoglycemia and hyperglycemia, depending on the individual's dietary state and overall health.

Ethanol metabolism leads to a higher NADH/NAD+ ratio in the liver, which inhibits fatty acid oxidation and the citric acid cycle (TCA cycle), resulting in the accumulation of fatty acids in the liver.

The accumulation of acetaldehyde, a toxic byproduct of ethanol metabolism, disrupts normal liver function by binding to various molecules like amino acids, sulfhydryl groups, nucleotides, and phospholipids.

Ethanol metabolism generates a higher NADH/NAD+ ratio, which shifts the equilibrium of oxaloacetate towards malate. This diverts acetyl-CoA away from the TCA cycle towards ketogenesis, leading to increased ketone body production.

Ethanol metabolism can increase the production of reactive oxygen species (free radicals), which can damage mitochondria and disrupt the electron transport chain. This further impairs acetaldehyde oxidation and overall liver function.

Disulfiram (Antabuse), an ALDH inhibitor, blocks the conversion of acetaldehyde to acetate. This causes unpleasant side effects upon alcohol consumption, discouraging future drinking.

The Microsomal Ethanol Oxidizing System (MEOS), a minor pathway of ethanol metabolism, becomes more relevant at higher alcohol concentrations.

Chronic alcohol consumption increases CYP2E1 activity in the MEOS pathway. This leads to faster alcohol breakdown, but it can also cause acetaldehyde accumulation, potentially leading to liver injury.

Ethanol metabolism results in an increase in the NADH/NAD+ ratio in the liver. This shift impacts various metabolic processes, potentially leading to fatty liver and other complications.