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The role of gluta-hydroxylase (Gpx) is to catalyze the reduction of glutathione, and therefore reduce the toxic reactive oxygen species that are produced by cytochrome C oxidase. Gpx is located within the mitochondria. Glutathione is a major antioxidant produced in the liver. Alcohol consumption causes oxidative stress in the brain. This stress causes fast depletion of glutamate, and decreases the functionality of NMDA receptors, which responds to glutamates. This change in Glu leads to the production of cytokine and ultimately results in inflammation and neurodegeneration. Glu also promotes the breakdown of ATP in the cell leading to more glutathione depletion.

When alcohol is metabolized by alcohol dehydrogenase (ADH), it passes through a series of steps to become acetaldehyde, which has a similar pharmacological effect as ethanol. Acetaldehyde is more reactive than ethanol, and also has the capacity to auto-oxidize to form formaldehyde causing further liver damage. Acetaldehyde causes a final destructive effect in the liver through a different pathway. Another chronic injury to liver tissue caused by alcohol is called steatosis, which is a toxic accumulation of fat in the liver, often in conjunction with other chronic liver conditions. Prolonged consumption of ethanol can cause hepatitis and cirrhosis. Production of ROS and depletion of glutathione, particularly in the mitochondria of liver cells, probably plays a major role in the pathophysiology of alcoholic liver injury. In chronically alcoholic rat liver diseases, Gpx expression and activity are markedly decreased, while the levels of glutathione are markedly depleted.

Following the introduction of alcohol to the CNS, the first effect is to depress the activity of the brain, including the sleep centers and the portions of the CNS that control comatose behavior and autopilot functions. This effect can result from the CNS depressant properties of alcohol, alcohol’s ability to inhibit the reuptake of dopamine into the CNS, the fact that binding of certain drugs and alcohol to proteins may alter the activity of other receptor proteins, and the fact that alcohol increases the activity of opiate peptides.

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