Topic
Steroid biosynthesis
About: Steroid biosynthesis is a research topic. Over the lifetime, 1721 publications have been published within this topic receiving 58977 citations.
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TL;DR: By analyzing the reactivity profiles of 896 P450 reactions, together with phylogenetic analysis, redox potential measurements, structural simulations, and a reaction matrix network, it is found that which pair of Fdx and FdR among multiple redox partners is the optimal one for a specific Class I P450 enzyme is often unclear.
Abstract: Cytochrome P450 enzymes are highly diversified biocatalysts associated with steroid biosynthesis, xenobiotic metabolism, biosynthesis of natural products, and industrial oxidation reactions. A typical P450 catalytic cycle requires sequential transfer of two electrons from NAD(P)H to the heme-iron reactive center for O2 activation. For the most abundant bacterial Class I P450 systems, this important process is usually mediated by two redox partner proteins including an FAD-containing ferredoxin reductase (FdR) and a small iron–sulfur protein, ferredoxin (Fdx). However, it is often unclear which pair of Fdx and FdR among multiple redox partners is the optimal one for a specific Class I P450 enzyme. To address this important but underexplored question, herein, a reaction matrix network with 16 Fdxs, 8 FdRs, and 6 P450s (against 7 substrates) was constituted. By analyzing the reactivity profiles of 896 P450 reactions, together with phylogenetic analysis, redox potential measurements, structural simulations, a...
67 citations
TL;DR: A novel Halloween gene is reported, noppera-bo (nobo), that encodes a member of the glutathione S-transferase family and raises the possibility that nobo plays a crucial role in regulating the behaviour of cholesterol in steroid biosynthesis in insects.
Abstract: In insects, the precise timing of moulting and metamorphosis is strictly guided by ecdysteroids that are synthesised from dietary cholesterol in the prothoracic gland (PG). In the past decade, several ecdysteroidogenic enzymes, some of which are encoded by the Halloween genes, have been identified and characterised. Here, we report a novel Halloween gene, noppera-bo (nobo), that encodes a member of the glutathione S-transferase family. nobo was identified as a gene that is predominantly expressed in the PG of the fruit fly Drosophila melanogaster. We generated a nobo knock-out mutant, which displayed embryonic lethality and a naked cuticle structure. These phenotypes are typical for Halloween mutants showing embryonic ecdysteroid deficiency. In addition, the PG-specific nobo knock-down larvae displayed an arrested phenotype and reduced 20-hydroxyecdysone (20E) titres. Importantly, both embryonic and larval phenotypes were rescued by the administration of 20E or cholesterol. We also confirm that PG cells in nobo loss-of-function larvae abnormally accumulate cholesterol. Considering that cholesterol is the most upstream material for ecdysteroid biosynthesis in the PG, our results raise the possibility that nobo plays a crucial role in regulating the behaviour of cholesterol in steroid biosynthesis in insects.
67 citations
TL;DR: A class of metabolic inhibitors which possess the ability to suppress the flowering of short-day plants and which appear to do so by interfering with generation of the flowering stimulus by the leaf are of further interest in that they are inhibitors of the biogenesis of steroids.
Abstract: This paper concerns a class of metabolic inhibitors
which possess the ability to suppress the flowering
of short-day plants and which appear to do
so by interfering with generation of the flowering
stimulus by the leaf. The inhibition of flowering
with which we are here concerned is thus different
from that elicited by 5-fluorouracil and 5-fluorodeoxyuridine.
These two substances act by preventing
successful receipt by the bud of the leaf-produced
floral stimulus (4, 17). The substances here reported
as active in inhibition of the generation of
flowering stimulus by the leaf are of further interest
in that they are inhibitors of the biogenesis of steroids.
67 citations
TL;DR: Data suggest that a specific allosteric binding site on b5, which includes residues E48, E49, and possibly R52, mediates the stimulation of 17,20-lyase activity.
Abstract: Cytochrome P450c17 (CYP17) catalyzes both the 17α-hydroxylase and 17,20-lyase reactions in human steroid biosynthesis. Cytochrome b5 (b5) stimulates the rate of the 17,20-lyase reaction 10-fold with little influence on 17α-hydroxylase activity. Studies with apo-b5 suggest that stimulation of 17,20-lyase activity results from an allosteric action on the hCYP17·POR complex, rather than electron transfer by b5. We hypothesized that specific residues on b5 interact with the hCYP17·POR complex and that targeted mutation of surface-exposed residues might identify b5 residues critical for stimulating 17,20-lyase activity. We constructed, expressed, and purified 14 single plus 3 double b5 mutations and assayed their ability to stimulate 17,20-lyase activity. Most mutations did not alter the capacity of b5 to stimulate 17,20-lyase activity or appeared to modestly alter the affinity of b5 for the hCYP17·POR complex. In contrast, mutation of E48, E49, or R52 reduced the maximal stimulation of 17,20-lyase activity. I...
67 citations
TL;DR: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites.
Abstract: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications.
67 citations