structure housing a hydrophobic pocket that holds cofactor NADPH and monoolein which occupies the steroid substrate binding pocket. In insect cells monoolein is not found, but is subbed out for other androgens and inhibitors. The integral seven transmembrane topology is likely conserved across species, with the N terminus in the endoplasmic reticulum lumen and the C terminus facing the cytosol. High conformational dynamics of the cytosolic region likely regulate NADPH/NADP+ exchange. Sequence conservation across known crystal structures has corroborated high conservation in enzyme structure. Inhibition The mechanism of 5α reductase inhibition is complex, but involves the binding of NADPH to the enzyme followed by the substrate. 5α-Reductase inhibitor drugs are used in benign prostatic hyperplasia, prostate cancer, pattern hair loss (androgenetic alopecia), and hormone replacement therapy for transgender women. Inhibition of the enzyme can be classified into two categories: steroidal, which are irreversible, and nonsteroidal. There are more steroidal inhibitors, with examples including finasteride (MK-906), dutasteride (GG745), 4-MA, turosteride, MK-386, MK-434, and MK-963. Researchers have pursued synthesis of nonsteroidals to inhibit 5α-reductase due to the undesired side effects of steroidals. The most potent and selective inhibitors of 5α-R1 are found in this class, and include benzoquinolones, nonsteroidal aryl acids, butanoic acid derivatives, and more recognizably, polyunsaturated fatty acids (especially linolenic acid), zinc, and green tea. Riboflavin was also identified as a 5α-reductase inhibitor . Additionally, it has been claimed that alfatradiol works through this mechanism of activity (5α-reductase), as well as the Ganoderic acids in lingzhi mushroom, and the Saw Palmetto. Inhibition of 5α-reductase results in decreased conversion of testosterone to DHT, leading to increased testosterone and estradiol. Other enzymes compensate to a degree for the absent conversion, specifically with local expression at the skin of reductive 17β-hydroxysteroid dehydrogenase, oxidative 3α-hydroxysteroid dehydrogenase, and 3β-hydroxysteroid dehydrogenase enzymes. Gynecomastia, erectile dysfunction, impaired cognitive function, fatigue, hypoglycemia, impaired liver function, constipation, and depression, are only a few of the possible side-effects of 5α-reductase inhibition. Long term side effects, that continued even after discontinuation of the drug have been reported. Finasteride Finasteride inhibits two 5α-reductase isoenzymes (II and III), while dutasteride inhibits all three. Finasteride potently inhibits 5α-R2 at a mean inhibitory concentration IC50 of 69 nM, but is less effective with 5α-R1 till an IC50 of 360 nM. Finasteride decreases mean serum level of DHT by 71% after 6 months, and was shown in vitro to inhibit 5α-R3 at a similar potency to