The implications of 7-dehydrosterol-7-reductase deficiency (Smith–Lemli–Opitz syndrome) to neurosteroid production

Oxidation of 7-dehydrocholesterol and desmosterol by human cytochrome P450 46A1

“…The enzyme effi ciency ( k cat / K m ) was similar for 7-dehydrocholesterol compared with cholesterol but 2-3 times higher than that of desmosterol. We note that although previous work by Björkhem et al ( 13 ) did not fi nd 7-dehydrocholesterol as a substrate of P450 46A1; their work was carried out in HEK293 cells, which presumably would metabolize 7-dehydrocholesterol to cholesterol effi ciently with intact cholesterol biosynthesis observed in the urine of SLOS patients, suggesting that 7-dehydrocholesterol is also a substrate of sterol side-chain cleavage enzyme (P450scc, P450 11A1) ( 41,42 ).…”

Malformation syndromes caused by disorders of cholesterol synthesis

“…The identifi ed dehydrosteroids and dehydrosteroid metabolites suggest that dehydrocholesterol can be transported into the mitochondria and participate in the following enzymatic reactions: p450 side chain cleavage, 17-hydroxylase/17,20-lyase, 3 ␤ -hydroxysteroid dehydrogenase , 3 ␣ -hydroxysteroid dehydrogenase, 17 ␤ -hydroxysteroid dehydrogenase, 20 ␣ -hydroxysteroid dehydrogenase, and 5 ␤ -reductase ( 144 ). A 7DHC derived analog of allopregnanolone, 7-dehydroallopregnanolone, has also been identifi ed in urine from postpubertal, female SLOS patients ( 101 ). Allopregnanolone is a neuroactive steroid.…”

Neuroendocrine System of the Skin

“…Alternatively, they may represent a new class of hormones/neurohormones at the peripheral or central level. Of note, the profound behavioral abnormalities of SLOS are thought to result from either production of Δ 7 unsaturated neurosteroid-like compounds [57], to which we may add vitDL compounds crossing the blood-brain barrier. The new P450scc activity on vitD adds a new potential site for the modification of vitD 3 bioactivity.…”