Cyp11a1 steroidogenesis

P450scc is always active, however its activity is limited by the supply of cholesterol in the inner membrane. The supplying of cholesterol to this membrane (from the outer mitochondrial membrane ) is, thus, considered the true rate-limiting step in steroid production. This step is mediated primarily by the steroidogenic acute regulatory protein (StAR or STARD1). Upon stimulation of a cell to make steroid, the amount of StAR available to transfer cholesterol to the inner membrane limits how fast the reaction can go (the acute phase). With prolonged (chronic) stimulation, it is thought that cholesterol supply becomes no longer an issue and that the capacity of the system to make steroid (., level of P450scc in the mitochondria) is now more important.

Biosynthesis of steroid hormones requires a battery of oxidative enzymes located in both mitochondria and endoplasmic reticulum. The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria. Within mitochondria, cholesterol is converted to pregnenolone by an enzyme in the inner membrane called CYP11A1. Pregnenolone itself is not a hormone, but is the immediate precursor for the synthesis of all of the steroid hormones. The following table delineates the enzymes required to synthesize the major classes of steroid hormones.

CYPs have been extensively examined in mice , rats , dogs , and less so in zebrafish , in order to facilitate use of these model organisms in drug discovery and toxicology . Recently CYPs have also been discovered in avian species, in particular turkeys, that may turn out to be a great model for cancer research in humans. [32] CYP1A5 and CYP3A37 in turkeys were found to be very similar to the human CYP1A2 and CYP3A4 respectively, in terms of their kinetic properties as well as in the metabolism of aflatoxin B1. [33]

Cyp11a1 steroidogenesis

cyp11a1 steroidogenesis

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