EVIDENCE FOR A DEFICIENCY OF STEROID A4-Sa-REDUCTASE ACTIVITY IN ACUTE INTERMITTENT PORPHYRIA* BY H. LEON BRADLOW,

I t was demonst ra ted in a preceding s tudy from these laboratories tha t pat ients with the genetic liver disease acute in termi t ten t porphyr ia (AIP) 1 display a significant defect in the reductive t ransformation of prototy~)e steroid hormones such as testosterone and dehydroisoandrosterone (1). This defect is manifest by the marked preferential metabol ism of these hormones along the 5 ~ p a t h w a y t h e pa thway through which endogenous steroids having a potent abi l i ty to induce the mitochondrial enzyme &aminolevul inate synthetase (ALAS) are generated (1-3). ALAS controls the rate-l imit ing step in porphyr in-heme synthesis (4) and has been found at high levels of ac t iv i ty in the livers of A I P pat ients (5). This excessive ac t iv i ty of hepat ic ALAS accounts for the overproduction of porphyr in precursors which characterizes this genetic disorder (6-8).