Hydroxylation of steroids by microorganisms

Because steroids are lipophilic, they diffuse easily through the cell membranes, and therefore have a very large distribution volume. In their target tissues, steroids are concentrated by an uptake mechanism which relies on their binding to intracellular proteins (or " receptors ", see below). High concentration of steroids are also found in adipose tissue, although this is not a target for hormone action. In the human male, adipose tissue contains aromatase activity, and seems to be the main source of androgen-derived estrogens found in the circulation. But most of the peripheral metabolism occurs in the liver and to some extent in the kidneys, which are the major sites of hormone inactivation and elimination, or catabolism (see below).

Due to membrane-bound CYP3A4's natural propensity to conglomerate, it has historically been difficult to study drug binding in both solution and on surfaces. Co-crystallization is difficult since the substrates tend to have a low Kd (between 5-150 μM) and low solubility in aqueous solutions. [33] A successful strategy in isolating the bound enzyme is the functional stabilization of monomeric CYP3A4 on Ag nanoparticles produced from nanosphere lithography and analyzed via localized surface plasmon resonance spectroscopy ( LSPR ). [34] These analyses can be used as a high-sensitivity assay of drug binding, and may become integral in further high-throughput assays utilized in initial drug discovery testing. In addition to LSPR, CYP3A4-Nanodisc complexes have been found helpful in other applications including solid-state NMR , redox potentiometry, and steady-state enzyme kinetics . [34]

Hydroxylation of steroids by microorganisms

hydroxylation of steroids by microorganisms


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