Endocrine Abstracts

Electron transfer mediated by proteins is a key process in nature.Many of the proteins involved in such electron transfers are complex and may require a number of redox active cofactors. In addition the electron-transfer steps themselves may add to the complexity by being coupled to other processes such as proton transfer and re-organisational changes. This is the case in the cytochromes P450 that function as steroidogenic enzymes. In fact, these enzymes...

P450 oxidoreductase (POR) has a pivotal role as electron donor to all cytochrome P450 enzymes that are microsomally located, i.e. CYP type II enzymes. Importantly, those include key enzymes involved in glucocorticoid and sex steroid biosynthesis such as CYP17 and CYP21. In addition, the activity of hepatic CYP enzymes involved in drug metabolism and detoxification also crucially depend on the transfer of electrons from NADPH via POR. Recently, mutations in P450 oxidoreductase ...

In the human adrenal cortex, three mitochondrial cytochromes P450 are involved in steroid hormone biosynthesis. CYP11A1 catalyses side-chain cleavage of cholesterol to yield pregnenolone, whereas P45011B1 is responsible for the conversion of 11-deoxycorticosterone and 11-deoxycortisol to the glucocorticoids, corticosterone and cortisol, respectively. The aldosterone synthase (CYP11B2) catalyses the 11β-hydroxylation, 18-hydroxylation and 18-oxidation of deoxycorticosteron...

Glucocorticoid (GC) hormone action can be modulated at the pre-receptor level by the endoluminal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). 11βHSD1 is a bidirectional enzyme that primarily acts as an oxo-reductase in vivo, converting the pro-hormone cortisone to its active form cortisol, while its dehydrogenase activity results in inactivation of cortisol to cortisone. 11βHSD1 oxo-reductase activity allows GC reactivation in a tissue s...