TY - JOUR T1 - The metabolism of 3,7-dimethyl-2,6-octadienal (citral) in rat hepatic mitochondrial and cytosolic fractions. Interactions with aldehyde and alcohol dehydrogenases. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 81 LP - 86 VL - 19 IS - 1 AU - C S Boyer AU - D R Petersen Y1 - 1991/01/01 UR - http://dmd.aspetjournals.org/content/19/1/81.abstract N2 - Citral (3,7-dimethyl-2,6-octadienal), a flavoring and fragrance agent, is associated with a variety of biochemical and toxicological effects. Reports of the in vivo metabolism of citral suggest that a primary route of metabolism is conversion to the corresponding acid species presumably by aldehyde dehydrogenases (ALDH). In the present study, hepatic mitochondrial and cytosolic fractions were prepared from male Sprague-Dawley rats to assess in vitro metabolism of citral. Evidence of ALDH-mediated citral oxidation was not seen in either subcellular fraction. On the contrary, citral was found to be a potent inhibitor of acetaldehyde oxidation by the low-KM mitochondrial form of ALDH. Measurement of the in vitro acetaldehyde oxidation rates of this isozyme in the presence of citral lead to the estimation of a Ki of 360 nM. Further studies of citral effects on low-KM mitochondrial ALDH indicate that inhibition is by a linear mixed-type mechanism and does not involve citral binding at the NAD+ binding site. In addition, it was observed that citral was readily reduced to the corresponding alcohol by alcohol dehydrogenase (ADH) in the cytosolic fraction. The reduction of citral in the presence of NADH proceeded at two distinct rates; an initial "fast" rate followed by a "slow" rate. Individual kinetic constants were calculated for the two rates. It is possible that the differential ADH-mediated reduction rates of citral are the result of varying affinities for the enzyme of the two citral isomers, geranial (trans) and neral (cis).(ABSTRACT TRUNCATED AT 250 WORDS) ER -