ascribed to this enzyme in brain has been in vitamin A metabolism, particularly the transformation of retinol to retinal. The retinal is transformed to retinoic acid which plays a major role in regulation of gene transcription. ADH5 has not been considered to be important in the metabolism of ethanol because of its reported high Km (low affinity) for ethanol (58). However, recent data have demonstrated that ADH5 activity with ethanol increases significantly if the enzyme activity is tested in a hydrophobic environment such as that encountered in hepatocytes or neurons (59). The Km for ethanol is reduced in hydrophobic solutions (59) and ADH5 becomes an important participant in the metabolism of ethanol at BAC of > 50 mM (~200 mg%) (60). It is interesting to note that the pharmacokinetic parameters of the early absorptive phase of ethanol metabolism show that ethanol (particularly if consumed on an empty stomach) partitions into brain and significantly higher concentrations of ethanol can be measured in brain as compared to blood in the early phases of ethanol administration. The implications for conversion of ethanol to acetaldehyde in brain have recently been detailed for rats bred to consume high levels of ethanol (61).
