scholarly journals Evidence for the involvement of 3-oxo-Δ4 intermediates in ecdysteroid biosynthesis

1996 ◽  
Vol 320 (2) ◽  
pp. 413-419 ◽  
Author(s):  
Catherine BLAIS ◽  
Chantal DAUPHIN-VILLEMANT ◽  
Nikolay KOVGANKO ◽  
Jean-Pierre GIRAULT ◽  
Charles DESCOINS ◽  
...  
Keyword(s):  
Bile Acid ◽  
Subcellular Localization ◽  
Biosynthetic Pathway ◽  
Steroid Hormone ◽  
Carcinus Maenas ◽  
Reduction Reaction ◽  
Acid Biosynthesis ◽  
Ecdysteroid Biosynthesis ◽  
Long Time

Although the involvement of 3-oxo-Δ4 compounds as intermediates in arthropod ecdysteroid biosynthesis has been postulated for a long time, it has not yet been directly demonstrated. In the present study, 3-oxo-Δ4-steroids have been synthesized and incubated in vitro with dissociated moulting gland cells from the crab Carcinus maenas. The tritiated compounds were converted into 3-dehydroecdysone, ecdysone and/or 25-deoxyecdysone, i.e. final ecdysteroids. This means that the 3-oxo-Δ4 compounds had undergone a 5β-reduction, to give the 5β-conformation of ecdysteroids. Our results suggest that the 3-oxo-Δ4-steroid 4,7-cholestadien-14α-ol-3,6-dione may be an intermediate in the biosynthetic pathway. The 5β-reduction reaction involves a cytosolic enzyme which requires NADPH as electron donor and seems specific for 3-oxo-Δ4 substrates. This reaction was the most active in crab Y-organs, as compared with other tissues. The characteristics of the 5β-reductase (subcellular localization, substrate and cofactor requirements) appear similar to those of the vertebrate 3-oxo-Δ4-steroid 5β-reductase involved in steroid hormone catabolism and bile acid biosynthesis.

scholarly journals METABOLIC PROFILE IN PLASMA AND CSF OF LEVODOPA-INDUCED DYSKINESIA OF PARKINSON’S DISEASE

2020 ◽  
Author(s):  
Bruno L. Santos-Lobato ◽  
Luiz Gustavo Gardinassi ◽  
Mariza Bortolanza ◽  
Ana Paula Ferranti Peti ◽  
Ângela V. Pimentel ◽  
...  
Keyword(s):  
Bile Acid ◽  
Metabolic Profile ◽  
Steroid Hormone ◽  
Untargeted Metabolomics ◽  
Acid Biosynthesis ◽  
Original Cohort ◽  
Metabolomics Data ◽  
Steroid Hormone Biosynthesis ◽  
Bile Acid Biosynthesis ◽  
Hormone Biosynthesis

Structured AbstractBackgroundThe existence of few biomarkers and the lack of a better understanding of the pathophysiology of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD) require new approaches, as the metabolomic analysis, for discoveries.ObjectivesWe aimed to identify a metabolic profile associated with LID in patients with PD in an original cohort, and to confirm the results in an external cohort (BioFIND).MethodsIn the original cohort, plasma and CSF were collected from 20 healthy controls, 23 patients with PD without LID, and 24 patients with PD with LID. LC-MS/MS and metabolomics data analysis were used to perform untargeted metabolomics. Untargeted metabolomics data from the BioFIND cohort were analyzed.ResultsWe identified a metabolic profile associated with LID in PD, composed of multiple metabolic pathways. In particular, the dysregulation of glycosphingolipids metabolic pathway was more related to LID and was strongly associated with the severity of dyskinetic movements. Further, bile acid biosynthesis and C21-steroid hormone biosynthesis metabolites simultaneously found in plasma and CSF have distinguished patients with LID from other participants. Levels of cortisol and cortisone were reduced in patients with PD and LID compared to patients with PD without LID. Data from the BioFIND cohort confirmed dysregulation in plasma metabolites from the bile acid biosynthesis and C21-steroid hormone biosynthesis pathways.ConclusionThere is a distinct metabolic profile associated with LID in PD, both in plasma and CSF, which may be associated with the dysregulation of lipid metabolism and neuroinflammation.

Bacterial deconjugation and enterohepatic circulation of norursocholic acid conjugates in rats

1991 ◽  
Vol 261 (6) ◽  
pp. G1065-G1071
Author(s):  
J. Lillienau ◽  
B. Borgstrom
Keyword(s):  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Cecal Content ◽  
Acid Biosynthesis ◽  
Bile Acid Pool ◽  
Distal Small Intestine ◽  
Acid Pool ◽  
System 2 ◽  
Small Intestinal

Experiments were performed to define the metabolism of norusocholic acid (nUC) conjugates and to quantify to what extent the bile acid pool can be enriched in these bile acids. In vitro incubations of norusocholylglycine (nUCG) and -taurine (nUCT) with small intestinal or cecal content showed deconjugation with only cecal content. Cholylglycine (CG) was deconjugated by small intestinal and cecal content. Infusion of nUCG and CG showed that only a small proportion of nUCG was deconjugated after 24 h of enterohepatic circulation, whereas all CG was deconjugated. When nUCT was administered orally, deconjugation was shown to take place mainly in the cecum. Chronic feeding of nUCT enriched the bile acid pool with only 20% nUCT. We conclude that nUC conjugates are deconjugated primarily by bacteria in the cecum and colon, in contrast to CG, which, in addition to cecum and colon, is deconjugated in the distal small intestine. nUCT and its metabolites do not enrich in the circulating bile acid pool mainly for the following reasons: 1) nUC conjugates have a low affinity for the ileal transport system; 2) nUC, even if formed by deconjugation, is not passively absorbed at a sufficient rate; 3) the small amount of norursodeoxycholic acid formed from nUC is glucuronidated in the liver and glucuronide conjugates do not undergo enterohepatic circulation; and 4) nUC conjugates do not suppress bile acid biosynthesis.

scholarly journals The role of sterol carrier protein2 and other hepatic lipid-binding proteins in bile-acid biosynthesis

1986 ◽  
Vol 238 (3) ◽  
pp. 879-884 ◽  
Author(s):  
B Lidström-Olsson ◽  
K Wikvall
Keyword(s):  
Bile Acid ◽  
Binding Proteins ◽  
Glutathione Transferase ◽  
Lipid Binding ◽  
Regulatory Function ◽  
Acid Biosynthesis ◽  
Fatty Acid Binding ◽  
Bile Acid Biosynthesis ◽  
Lipid Binding Proteins

The ability of different lipid-binding proteins in liver cytosol to affect enzyme activities in bile-acid biosynthesis was studied in whole microsomes (microsomal fractions) and mitochondria and in purified enzyme systems. Sterol carrier protein2 stimulated the 7 alpha-hydroxylation of cholesterol and the 12 alpha-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha-diol in microsomes and the 26-hydroxylation of cholesterol in mitochondria 2-3-fold. It also stimulated the oxidation of 5-cholestene-3 beta, 7 alpha-diol into 7 alpha-hydroxy-4-cholesten-3-one in microsomes. The stimulatory effect of sterol carrier protein2 was much less with purified cholesterol 7 alpha- and 26-hydroxylase systems than with microsomes and mitochondria. No stimulatory effect of sterol carrier protein2 was observed with purified 12 alpha-hydroxylase and 3 beta-hydroxy-delta 5-C27-steroid oxidoreductase. Sterol carrier protein (fatty-acid-binding protein), ‘DEAE-peak I protein’ [Dempsey, McCoy, Baker, Dimitriadou-Vafiadou, Lorsbach & Howards (1981) J. Biol. Chem. 256, 1867-1873], ligandin (glutathione transferase B) and serum albumin had no marked stimulatory effects in either crude or in purified systems. The results suggest that sterol carrier protein2 facilitates the introduction of the less-polar substrates in bile-acid biosynthesis to the membrane-bound enzymes in crude systems in vitro. The broad substrate specificity appears, however, not to be consistent with a specific regulatory function for sterol carrier protein2 in bile-acid biosynthesis.

STEROID HORMONE METABOLISM IN RESPONSIVE TISSUES IN VITRO

1971 ◽  
Vol 68 (1_Suppl) ◽  
pp. S279-S294 ◽  
Author(s):  
Paul Robel
Keyword(s):  
Steroid Hormone ◽  
Physiological Activity ◽  
Physiological State ◽  
Target Cells ◽  
Target Tissue ◽  
Hormone Metabolism ◽  
Metabolizing Enzymes ◽  
Relationship Of

ABSTRACT Of the information available on steroid hormone metabolism in responsive tissues, only that relating hormone metabolism to physiological activity is reviewed, i. e. metabolite activity in isolated in vitro systems, binding of metabolites to target tissue receptors, specific steroid hormone metabolizing enzymes and relationship of hormone metabolism to target organ physiological state. Further, evidence is presented in the androgen field, demonstrating 5α-reduced metabolites, formed inside the target cells, as active compounds. This has led to a consideration of testosterone as a »prehormone«. The possibility that similar events take place in tissues responding to progesterone is discussed. Finally, the role of hormone metabolism in the regulation of hormone availability and/or renewal in target cells is discussed. In this context, reference is made to the potential role of plasma binding proteins and cytosol receptors.

The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment

2018 ◽  
Vol 18 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Michael Keidar
Keyword(s):  
Cancer Treatment ◽  
Atmospheric Plasma ◽  
Current Status ◽  
Cold Atmospheric Plasma ◽  
Anti Cancer ◽  
Long Time ◽  
Key Topics ◽  
The Common

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

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