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.

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