Alcohol Malate aspartate

The final reactions to be considered in the metabolism of ethanol in the liver are those involved in reoxidation of cytosolic NADH and in the reduction of NADP. The latter is achieved by the pentose phosphate pathway which has a high capacity in the liver (Chapter 6). The cytosolic NADH is reoxidised mainly by the mitochondrial electron transfer system, which means that substrate shuttles must be used to transport the hydrogen atoms into the mitochondria. The malate/aspartate is the main shuttle involved. Under some conditions, the rate of transfer of hydrogen atoms by the shuttle is less than the rate of NADH generation so that the redox state in the cytosolic compartment of the liver becomes highly reduced and the concentration of NAD severely decreased. This limits the rate of ethanol oxidation by alcohol dehydrogenase. 

Why might one expect the activity of the malate-aspartate shuttle to be changed by alcohol consumption (See Sugano cf of., 1990.)... 

Alcohol dehydrogenase, a cytosolic enzyme, catalyzes the oxidation of ethanol to acetaldehyde with the generation of NADH. The energy from this NADH is transferred to mitochondria, primarily by means of the malate-aspartate shuttle. When an alcoholic consumes over 50% of his or her energy in the form of alcohol, this shuttle becomes vastly important. Most of the acetaldehyde is oxidized in the mitochondria by mitochondrial aldehyde dehydrogenase, though a cytosolic version of the enzyme also exists. These reactions are shown in Figure 4.69. 

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