Explain the toxic effects of excessive ethanol consumption on metabolism. In your answer, explain both the toxicity of ethanol metabolites at a molecular level and the specific effects of ethanol degradation on the major pathways we have studied (e. g., glycolysis, Krebs cycle, and the pentose phosphate pathway, to name a few).

The toxicity of alcohol is due to its metabolisms to acetaldehyde in cells of the body especially the liver, formation of free radicals and reactive molecules (oxygen and nitrogen species) e. g hydroxyl radicals, nitric acids., exhaustion of co-factors (NAD+, FAD+) in the cells, and loss of energy mechanisms. Most body tissues metabolize alcohol to acetaldehyde, because there is a significant redundance in its oxidative enzymatic pathways. However the liver is the major site (because of its detoxification role) where the toxic effect causes fatty liver diseases.

Alcohol also distort the integrity of the mucosal barrier of the GI tracts. This effects produced activation of immune response as a result of translocation of endotoxin from gut bacteria to the liver through the hepatic portal artery. The antigenic effect of these toxins elicited the response.

Acetaldehyde and reactive molecules disrupts the molecular structure of DNA, protein tertiary structure, and lipids. It causes oxidative stress. The dissipation of Co-factors NAD + FAD + and disruption of cell signal pathways and ion channels affects hepatic respiration in the liver mitochondrial and metabolism of lipids, This leads to hypoxia.

Consequently, glycolytic pathway in the Cytosol and the citric acid pathways in the mitochondrial are slowed down and since co factors for the transfer of electrons for redox reactions are wasted. With the drop in ATPs production, ion channels transport is affected (no active transport). This leads to cell deaths eliciting more innate immune response.