Steroids, endogenous metabolism

Jansson I, Stoilov I, Sarfarazi M, Schenkman JB. 2001. Effect of two mutations of human CYPIBI, G61E and R469W, on stability and endogenous steroid substrate metabolism. Pharmacogenetics 11 793-801. 

Adlercreutz, H. (1977). Quantitative mass spectrometry of endogenous and exogenous steroids in metabolic studies in man. In "Quantitative Mass Spectrometry in Life Sciences (A. P. De Leenheer and R. R. Roncucci, eds.), Vol. 1, pp. 15-28. Elsevier, Amsterdam. 

Exposure to estrogenic compounds through diet will differ for herbivores and carnivores, the latter being most likely to encounter endogenous steroids in their prey. Efficient uptake of steroids in mammals is illustrated by the use of the contraceptive pill, but routes of absorption in invertebrates remain to be determined. The relationship between endocrine disruption and metabolic toxicity, with reduced reproductive viability a secondary consequence of metabolic disturbance, also merits further study in invertebrate species. 

Involved In the metabolism of many endogenous compounds (eg, steroids)... 

Phytoestrogens may also modulate the concentration of endogenous steroid hormones by binding to and inactivating the enzymes involved in their biosynthesis and metabolism. 

Not unexpectedly, cycloalkene oxides are equally important as alkene oxides in medicinal chemistry and drug metabolism, as illustrated below with a few selected examples. Other compounds of interest that will not be discussed here include epoxytetrahydrocannabinols and endogenous 16,17-ep-oxy steroids. 

A variety of endogenous and synthetic steroids have now been demonstrated to alter neuronal activity. Paul and Purdy (1992) proposed that this group of neurosteroids be named neuroactive steroids, a nomenclature defining their activity. Further complicating this terminology, some authors more generally define neurosteroids both as neuroactive compounds produced de novo in the nervous system and as those steroids derived from circulating precursors, which are metabolized to neuroactive compounds in the nervous system. 

The cytochrome P450 (CYP450) enzyme superfamily is the primary phase I enzyme system involved in the oxidative metabolism of drugs and other chemicals. These enzymes also are responsible for all or part of the metabolism and synthesis of a number of endogenous compounds, such as steroid hormones and prostaglandins. 

Sulfotransferases (SULTs) are important for the metabolism of a number of drugs, neurotransmitters, and hormones, especially the steroid hormones. The cosubstrate for these reactions is 3 -phosphoadenosine 5 -phosphosulfate (PAPS) (Fig. 4.1). Like the aforementioned enzymes, sulfate conjugation typically renders the compound inactive and more water soluble. However, this process can also result in the activation of certain compounds, such as the antihypertensive minoxidil and several of the steroid hormones. Seven SULT isoforms identified in humans, including SULTs lAl to 1A3, possess activity toward phenolic substrates such as dopamine, estradiol, and acetaminophen. SULTIBI possesses activity toward such endogenous substrates as dopamine and triiodothyronine. SULTIEI has substantial activity toward steroid hormones, especially estradiol and dehydroepiandrosterone, and toward the anti-... 

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