Topic
Pregnenolone
About: Pregnenolone is a research topic. Over the lifetime, 3539 publications have been published within this topic receiving 126444 citations. The topic is also known as: (3b)-3-hydroxy-Pregn-5-en-20-one & 3-Hydroxypregn-5-en-20-one.
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TL;DR: It is determined that fetal alcohol exposure alters the actions of the neurosteroids pregnenolone sulfate and pregnanolone hemisuccinate, which potentiate NMDA receptor function, and in utero ethanol exposure did not affect theactions of neurosteroid that inhibit NMDA receptors.
45 citations
TL;DR: The results suggest that Atf2p (APAT) plays an active role in the detoxification of 3β-hydroxysteroids in association with the efflux pumps Pdr5p and Snq2p.
Abstract: While studying the effect of steroids on the growth of the yeast Saccharomyces cerevisiae, we found that pregnenolone was converted into the acetate ester. This reaction was identified as a transfer of the acetyl group from acetyl-CoA to the 3β-hydroxyl group of pregnenolone. The corresponding enzyme, acetyl-CoA:pregnenolone acetyltransferase (APAT) is specific for Δ5- or Δ4-3β-hydroxysteroids and short-chain acyl-CoAs. The apparent Km for pregnenolone is ≈0.5 µm. The protein associated with APAT activity was partially purified and finally isolated from an SDS/polyacrylamide gel. Tryptic peptides were generated and N-terminally sequenced. Two peptide sequences allowed the identification of an open reading frame (YGR177c, in the S. cerevisiae genome database) translating into a 62-kDa protein of hitherto unknown function. This protein encoded by a gene known as ATF2 displays 37% identity with an alcohol acetyltransferase encoded by the yeast gene ATF1. Disruption of ATF2 led to the complete elimination of APAT activity and consequently abolished the esterification of pregnenolone. In addition, a toxic effect of pregnenolone linked to the disruption of ATF2 was observed. Pregnenolone toxicity is more pronounced when the atf2-Δ mutation is introduced in a yeast strain devoid of the ATP-binding cassette transporters, PDR5 and SNQ2. Our results suggest that Atf2p (APAT) plays an active role in the detoxification of 3β-hydroxysteroids in association with the efflux pumps Pdr5p and Snq2p.
45 citations
TL;DR: The finding that sulphoconjugated 5alpha-androstenone was present in large amounts suggests that this steroid may be converted from a3-keto to a 3-enol form which is subsequently sulphconjugated.
45 citations
TL;DR: The results support the previously advanced hypothesis that the true intermediates in the side chain cleavage of cholesterol are reactive complexes of a metalloenzyme and oxygenated steroidal species, and not free hydroxylated compounds.
45 citations
TL;DR: It is shown that HST is the major sulphotransferase responsible for the sulphation of DHEA, androsterone and pregnenolone in man and that, functionally, the hepatic and adrenal enzymes are very similar.
45 citations