scholarly journals The in vivo hydrocarbon formation by vanadium nitrogenase follows a secondary metabolic pathway

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Johannes G. Rebelein ◽  
Chi Chung Lee ◽  
Yilin Hu ◽  
Markus W. Ribbe
Keyword(s):  
Metabolic Pathway ◽  
Secondary Metabolic Pathway ◽  
Hydrocarbon Formation ◽  
Vanadium Nitrogenase

scholarly journals A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jong Bong Lee ◽  
Masar Radhi ◽  
Elena Cipolla ◽  
Raj D. Gandhi ◽  
Sarir Sarmad ◽  
...  
Keyword(s):  
Oral Administration ◽  
Metabolic Pathway ◽  
Oral Absorption ◽  
Therapeutic Effects ◽  
The Novel ◽  
Drug Candidates ◽  
Biopharmaceutical Properties

Abstract Although adenosine and its analogues have been assessed in the past as potential drug candidates due to the important role of adenosine in physiology, only little is known about their absorption following oral administration. In this work, we have studied the oral absorption and disposition pathways of cordycepin, an adenosine analogue. In vitro biopharmaceutical properties and in vivo oral absorption and disposition of cordycepin were assessed in rats. Despite the fact that numerous studies showed efficacy following oral dosing of cordycepin, we found that intact cordycepin was not absorbed following oral administration to rats. However, 3′-deoxyinosine, a metabolite of cordycepin previously considered to be inactive, was absorbed into the systemic blood circulation. Further investigation was performed to study the conversion of 3′-deoxyinosine to cordycepin 5′-triphosphate in vitro using macrophage-like RAW264.7 cells. It demonstrated that cordycepin 5′-triphosphate, the active metabolite of cordycepin, can be formed not only from cordycepin, but also from 3′-deoxyinosine. The novel nucleoside rescue metabolic pathway proposed in this study could be responsible for therapeutic effects of adenosine and other analogues of adenosine following oral administration. These findings may have importance in understanding the physiology and pathophysiology associated with adenosine, as well as drug discovery and development utilising adenosine analogues.

scholarly journals In vivo functional analysis of L-rhamnose metabolic pathway in Aspergillus niger: a tool to identify the potential inducer of RhaR

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Claire Khosravi ◽  
Roland Sándor Kun ◽  
Jaap Visser ◽  
María Victoria Aguilar-Pontes ◽  
Ronald P. de Vries ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Aspergillus Niger ◽  
Metabolic Pathway

scholarly journals When cholesterol meets histamine, it gives rise to dendrogenin A: a tumour suppressor metabolite1

2016 ◽  
Vol 44 (2) ◽  
pp. 631-637 ◽  
Author(s):  
Marc Poirot ◽  
Sandrine Silvente-Poirot
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Metabolic Pathway ◽  
Protective Role ◽  
Tumour Suppressor ◽  
Human Tissues ◽  
Normal Tissues ◽  
Steroidal Alkaloid

Dendrogenin A (DDA) is the first steroidal alkaloid (SA) to be identified in human tissues to date and arises from the stereoselective enzymatic conjugation of 5,6α-epoxycholesterol (5,6α-EC) with histamine (HA). DDA induces the re-differentiation of cancer cells in vitro and in vivo and prevents breast cancer (BC) and melanoma development in mice, evidencing its protective role against oncogenesis. In addition, DDA production is lower in BCs compared with normal tissues, suggesting a deregulation of its biosynthesis during carcinogenesis. The discovery of DDA reveals the existence of a new metabolic pathway in mammals which lies at the crossroads of cholesterol and HA metabolism and which leads to the production of this metabolic tumour suppressor.

scholarly journals Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE

2021 ◽  
Vol 11 ◽  
Author(s):  
Yifan Zhao ◽  
Peng Sun ◽  
Yue Ma ◽  
Xiaoqiang Chang ◽  
Xingyu Chen ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Red Blood Cells ◽  
Metabolic Pathway ◽  
Blood Cells ◽  
Metabolite Profiling ◽  
First Line ◽  
First Time ◽  
Insight Into ◽  
Tof Ms

Dihydroartemisinin (DHA) and its’ derivatives have been employed as the most powerful first-line drugs for malarial treatment for several decades. The metabolism of DHA has not been studied clearly. Previous reports were focused on the pharmacokinetics procedure of DHA in healthy rats. The metabolites of DHA in red blood cells (RBC), especially in the RBC from Plasmodium-infected models, have rarely been studied. The Plasmodium species parasitize inside RBC, and these cells should be the final place where DHA performs its activity. In this study, the profile of DHA metabolites in biosample (blood, plasma, and RBC) of the infected and healthy mice was investigated with UPLC-Q-TOF-MS and UNIFI platform to gain insight into DHA metabolism. Results show that a total of 25 metabolites were successfully identified in infected (30 in healthy) blood, 27 in infected (27 in healthy) plasma, and 15 in infected (22 in healthy) RBC. Results show that hydroxylation, OH-dehydration, and glucuronidation reactions were important in the metabolic pathway in vivo. Significantly, DHA metabolites inside RBC were identified for the first time. 8-Hydroxy (8-OH) DHA, 4α-OH deoxy ART, and 6β-OH deoxy ART were identified in vivo for the first time.

scholarly journals Expression of Indoleamine 2,3-Dioxygenase, Tryptophan Degradation, and Kynurenine Formation during In Vivo Infection with Toxoplasma gondii: Induction by Endogenous Gamma Interferon and Requirement of Interferon Regulatory Factor 1

2002 ◽  
Vol 70 (2) ◽  
pp. 859-868 ◽  
Author(s):  
Neide M. Silva ◽  
Cibele V. Rodrigues ◽  
Marcelo M. Santoro ◽  
Luiz F. L. Reis ◽  
Jacqueline I. Alvarez-Leite ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Mrna Expression ◽  
Metabolic Pathway ◽  
Acute Infection ◽  
Regulatory Factor ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tryptophan Degradation ◽  
Ifn Γ ◽  
Oxide Synthase

ABSTRACT The induction of indoleamine 2,3-dioxygenase (INDO) expression and the tryptophan (Trp)-kynurenine (Kyn) metabolic pathway during in vivo infection with Toxoplasma gondii was investigated. Decreased levels of Trp and increased formation of Kyn were observed in the lungs, brain, and serum from mice infected with T. gondii. Maximal INDO mRNA expression and enzyme activity were detected in the lungs at 10 to 20 days postinfection. Further, the induction of INDO mRNA expression, Trp degradation and Kyn formation were completely absent in tissues from mice deficient in IFN-γ (IFN-γ−/−) or IFN regulatory factor -1 (IRF-1−/−). These findings indicate the important role of endogenous IFN-γ and IRF-1 in the in vivo induction of the Trp-Kyn metabolic pathway during acute infection with T. gondii. In contrast, expression of INDO mRNA and its activity was preserved in the tissues of TNF-receptor p55- or inducible nitric oxide synthase-deficient mice infected with T. gondii. Together with the results showing the extreme susceptibility of the IFN-γ−/− and the IRF-1−/− mice to infection with T. gondii, our results indicate a possible involvement of INDO and Trp degradation in host resistance to early infection with this parasite.

ETUDES IN VIVO. SUR LE METABOLISME DES ANDROGENES APRES ADMINISTRATION DE STEROIDES INHIBITEURS DE L'OVULATION

1966 ◽  
Vol 53 (1) ◽  
pp. 37-52 ◽  
Author(s):  
Pierre Mauvais-Jarvis
Keyword(s):  
Dehydrogenase Activity ◽  
Metabolic Pathway ◽  
Urinary Metabolites ◽  
Hydroxysteroid Dehydrogenase ◽  
Before And After ◽  
Normal Men ◽  
Ethinyl Oestradiol

ABSTRACT Radioactive dehydroepiandrosterone sulfate and testosterone, which are two circulating compounds in humans, have been injected into normal men, women and patients with Stein-Leventhal syndrome. These injections were made before and after administration of ethinyl-oestradiol, lynoestrenol and association of lynoestrenol and mestranol (Lyndiol®). The per cent conversion of injected steroids into 17-ketonic and 17β-hydroxylated urinary metabolites was calculated. The results observed can be summarized as follows: in all cases, the yields of sulfate metabolites formed from radioactive precursors were more important after treatment by antiovulatory steroids, especially urinary dehydroepiandrosterone sulfate derived from injected dehydroepiandrosterone sulfate: aetiocholanolone and androsterone formed from testosterone. The modifications in the 5β/5α ratio of androstanediols suggest that oral synthetic oestrogens and progestins inhibit the 5α-Δ4 reductase implicated in the »17β-hydroxyl metabolic pathway« of testosterone. A change in 17β-hydroxysteroid dehydrogenase activity is also postulated, because testosterone was more metabolized into androsterone via androstenedione, and less reduced into androstanediol after antiovulatory steroids.

scholarly journals The conversion of 4-hydroxypyrazolo-[3,4-d]pyrimidine (allopurinol) into 4,6-dihydroxypyrazolo[3,4-d]pyrimidine (oxipurinol) in vivo in the absence of xanthine–oxygen oxidoreductase

1969 ◽  
Vol 112 (4) ◽  
pp. 527-532 ◽  
Author(s):  
R. A. Chalmers ◽  
R. Parker ◽  
H A Simmonds ◽  
W. Snedden ◽  
R. W. E. Watts
Keyword(s):  
Mass Spectrometry ◽  
Xanthine Oxidase ◽  
Infrared Spectra ◽  
Metabolic Pathway ◽  
Mass Spectra ◽  
Mass Spectrometric ◽  
Spectrometric Investigation ◽  
Mass Spectrometric Investigation ◽  
Congenital Deficiency

1. A patient with congenital deficiency of xanthine oxidase (EC 1.2.3.2) (xanthinuria) excreted the xanthine isomer 4,6-dihydroxypyrazolo[3,4-d]pyrimidine (oxipurinol) in his urine when the hypoxanthine isomer 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) was given by mouth. 2. The identity of the oxipurinol that the patient excreted was established by mass spectrometry. 3. The mass spectra and infrared spectra of allopurinol, oxipurinol, hypoxanthine and xanthine are compared. 4. A mechanism for the fragmentation of these compounds that occurs during their mass-spectrometric investigation is proposed. 5. A possible metabolic pathway for the oxidation of allopurinol to oxipurinol in the absence of xanthine oxidase is discussed.

scholarly journals Discovery of a widespread metabolic pathway within and among phenolic xenobiotics

2017 ◽  
Vol 114 (23) ◽  
pp. 6062-6067 ◽  
Author(s):  
Pahriya Ashrap ◽  
Guomao Zheng ◽  
Yi Wan ◽  
Tong Li ◽  
Wenxin Hu ◽  
...  
Keyword(s):  
Phase I ◽  
Metabolic Pathway ◽  
Parent Compound ◽  
Water Soluble ◽  
Chlorinated Phenols ◽  
Cytochrome P450 Enzymes ◽  
Rapid Phase ◽  
Phenolic Pollutants

Metabolism is an organism’s primary defense against xenobiotics, yet it also increases the production of toxic metabolites. It is generally recognized that phenolic xenobiotics, a group of ubiquitous endocrine disruptors, undergo rapid phase II metabolism to generate more water-soluble glucuronide and sulfate conjugates as a detoxification pathway. However, the toxicological effects of the compounds invariably point to the phase I metabolic cytochrome P450 enzymes. Here we show that phenolic xenobiotics undergo an unknown metabolic pathway to form more lipophilic and bioactive products. In a nontargeted screening of the metabolites of a widely used antibacterial ingredient: triclosan (TCS), we identified a metabolic pathway via in vitro incubation with weever, quail, and human microsomes and in vivo exposure in mice, which generated a group of products: TCS-O-TCS. The lipophilic metabolite of TCS was frequently detected in urine samples from the general population, and TCS-O-TCS activated the constitutive androstane receptor with the binding activity about 7.2 times higher than that of the parent compound. The metabolic pathway was mediated mainly by phase I enzymes localized on the microsomes and widely observed in chlorinated phenols, phenols, and hydroxylated aromatics. The pathway was also present in different phenolic xenobiotics and formed groups of unknown pollutants in organisms (e.g., TCS-O-bisphenol A and TCS-O-benzo(a)pyrene), thus providing a cross-talk reaction between different phenolic pollutants during metabolic processes in organisms.

scholarly journals Fatty acid photodecarboxylase is an ancient photoenzyme responsible for hydrocarbon formation in the thylakoid membranes of algae

2020 ◽  
Author(s):  
Solène Moulin ◽  
Audrey Beyly ◽  
Stéphanie Blangy ◽  
Bertrand Légeret ◽  
Magali Floriani ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Growth Conditions ◽  
Secondary Endosymbiosis ◽  
Chlorella Variabilis ◽  
Green Microalga ◽  
Specific Subgroup ◽  
Hydrocarbon Formation

ABSTRACTFatty acid photodecarboxylase (FAP) is one of the three enzymes that require light for their catalytic cycle (photoenzymes). FAP has been first identified in the green microalga Chlorella variabilis NC64A and belongs an algae-specific subgroup of the glucose-methanol-choline oxidoreductase family. While the FAP from Chlorella and its Chlamydomonas reinhardtii homolog CrFAP have demonstrated in vitro activity, their activity and physiological function have not been studied in vivo. Besides, the conservation of FAP activity beyond green microalgae remains hypothetical. Here, using a Chlamydomonas FAP knockout line (fap), we show that CrFAP is responsible for the formation of 7-heptadecene, the only hydrocarbon present in this alga. We further show that CrFAP is associated to the thylakoids and that 90% of 7-heptadecene is recovered in this cell fraction. In the fap mutant, photosynthesis activity was not affected under standard growth conditions but was reduced after cold acclimation. A phylogenetic analysis including sequences from Tara Ocean identified almost 200 putative FAPs and indicated that FAP was acquired early after primary endosymbiosis. Within Bikonta, FAP was kept in photosynthetic secondary endosymbiosis lineages but absent in those that lost the plastid. Characterization of recombinant FAPs from various algal genera (Nannochloropsis, Ectocarpus, Galdieria, Chondrus) provided experimental evidence that FAP activity is conserved in red and brown algae and is not limited to unicellular species. These results thus indicate that FAP has been conserved during evolution of most algal lineages when photosynthesis was kept and suggest that its function is linked to photosynthetic membranes.One sentence summaryFAP is present in thylakoids and conserved beyond green algae.

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