Alcohol Dehydrogenase Isoenzymes

ADH is a zinc metalloprotein with five classes of isoenzymes that arise from the association of eight different subunits into dimers (Table 5). A genetic model accounts for these five classes of ADH as

Acetate

Acetaldehyde

Figure 2 Chemical structures of acetaldehyde and acetate, the products of ethanol metabolism.

Figure 3 Pathways of ethanol metabolism.

products of five gene loci (ADH1-5). Class 1 isoenzymes generally require a low concentration of ethanol to achieve 'half-maximal activity' (low Km), whereas class 2 isoenzymes have a relatively high Km. Class 3 ADH has a low affinity for ethanol and does not participate in the oxidation of ethanol in the liver. Class 4 ADH is found in the human stomach and class 5 has been reported in liver and

Table 5 Classes of alcohol dehydrogenase isoenzymes

Class

Subunit

Location

Km (mmol/lf

Vmax

ADH1 ADH2 ADH3

Liver, lung Liver, stomach

0.05-34 0.6-1.0

54

ADH4

n

Liver, cornea

34

40

ADH5

X

Most tissues

1000

ADH7

a, m

Stomach, oesophagus, other mucosae

20

1510

ADH6

Liver, stomach

30

aKm supplied is for ethanol; ADH 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.

aKm supplied is for ethanol; ADH 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.

stomach. Whereas the majority of ethanol metabolism occurs in the liver, gastric ADH is responsible for a small portion of ethanol oxidation.

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