Acetaldehyde Metabolism

Acetaldehyde is highly toxic but is rapidly converted to acetate. This conversion is catalyzed by aldehyde

Table 6 Classes of aldehyde dehydrogenase isoenzymes

Class

Structure Location

Km famol/l)a

ALDH1

ALDH2

a4 Cytosolic

Many tissues: highest 30 in liver a4 Mitochondrial

Present in all tissues 1

except red blood cells

Liver > kidney > muscle > heart aKm supplied is for acetaldehyde; ALDH also oxidizes other substrates.

Adapted with permission from Kwo PY and Crabb DW (2002) Genetics of ethanol metabolism and alcoholic liver disease. In: Sherman DIN, Preedy VR and Watson RR (eds.) Ethanol and the Liver. Mechanisms and Management, pp. 95-129. London: Taylor & Francis.

dehydrogenase (ALDH) and is accompanied by reduction of NAD+ (Figure 3). There are several isoenzymes of ALDH (Table 6). The most important are ALDH1 (cytosolic) and ALDH2 (mitochon-drial). The presence of ALDH in tissues may reduce the toxic effects of acetaldehyde.

In alcoholics, the oxidation of ethanol is increased by induction of MEOS. However, the capacity of mitochondria to oxidize acetaldehyde is reduced. Hepatic acetaldehyde therefore increases with chronic ethanol consumption. A significant increase of acetaldehyde in hepatic venous blood reflects the high tissue level.

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