Human aldehyde dehydrogenase: metabolism of putrescine and histamine.

Imidazoleacetaldehyde and gamma-aminobutyraldehyde, metabolites of histamine and putrescine, respectively, have been shown to be substrates of human liver aldehyde dehydrogenase (EC 1.2.1.3) cytoplasmic (E1) and mitochondrial (E2) isozymes. The Km values at pH 7.4 and 500 microM NAD for imidazoleacetaldehyde and gamma-aminobutyraldehyde for the E1 isozyme are 40 and 800 microM, respectively, and for the E2 isozyme are 50 and 500 microM, respectively. The Km values with gamma-aminobutyraldehyde with both isozymes are high relative to Km values with acetaldehyde (50 microM for E1 and 1 microM for E2). Since activity with both imidazoleacetaldehyde and gamma-aminobutyraldehyde in crude liver homogenates paralleled that of aldehyde dehydrogenase (EC 1.2.1.3) during purification it appears likely that in the human liver this enzyme is responsible for metabolism of both compounds. If this is the case, interaction between metabolism of histamine and putrescine and that of alcohol is likely. Both imidazoleacetaldehyde and gamma-aminobutyraldehyde were synthesized in this laboratory and their stability has been investigated. Procedures for assaying aldehyde dehydrogenase employing synthetic metabolites of histamine and putrescine are provided.