Potent reductase

The most significant metabolic product of testosterone is DHT, since in many tissues, including prostate, external genitalia, and some areas of the skin, this is the active form of the hormone. The plasma content of DHT in the adult male is about one-tenth that of testosterone, and approximately 400 ig of DHT is produced daily as compared with about 5 mg of testosterone. About 50-100 ig of DHT are secreted by the testes. The rest is produced peripherally from testosterone in a reaction catalyzed by the NADPH-depen-dent 5oi-reductase (Figure 42-6). Testosterone can thus be considered a prohormone, since it is converted into a much more potent compound (dihydrotestosterone) and since most of this conversion occurs outside the testes. Some estradiol is formed from the peripheral aromatization of testosterone, particularly in males. 

H)2-D3 is a weak agonist and must be modified by hydroxylation at position Cj for full biologic activity. This is accomplished in mitochondria of the renal proximal convoluted tubule by a three-component monooxygenase reaction that requires NADPFl, Mg, molecular oxygen, and at least three enzymes (1) a flavoprotein, renal ferredoxin reductase (2) an iron sulfur protein, renal ferredoxin and (3) cytochrome P450. This system produces l,25(OH)2-D3, which is the most potent namrally occurring metabolite of vitamin D. 

Heidel JD, Liu JY, Yen Y, Zhou B, Heale BS, Rossi JJ, Bartlett DW, Davis ME (2007) Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin Cancer Res 13 2207-2215... 

The synthesis of the decalin unit of compactin (59), a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which acts as an effective hypocholesterolemic agent, was planned to incorporate an intramolecular Diels-Alder reaction (Scheme 9.15) [57]. 

K., Wachter, H., Werner-Felmayer, G., Mayer, B., Identification of the 4-amino analogue of tetrahydrobiopterin as a dihydropteridine reductase inhibitor and a potent pteridine antagonist of rat neuronal nitric oxide synthase, Biochem. J. 320 (1996), p. 193-196... 

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