ATP7A-Regulated Enzyme Metalation and Trafficking in the Menkes Disease Puzzle DOI Creative Commons
Nina Horn, Pernilla Wittung‐Stafshede

Biomedicines, Journal Year: 2021, Volume and Issue: 9(4), P. 391 - 391

Published: April 6, 2021

Copper is vital for numerous cellular functions affecting all tissues and organ systems in the body. The copper pump, ATP7A critical whole-body, cellular, subcellular homeostasis, dysfunction due to genetic defects results Menkes disease. leads deficiency nervous tissue, liver, blood but accumulation other tissues. Site-specific deficiencies of lead loss function copper-dependent enzymes tissues, range disease pathologies observed can now be explained full by lack specific enzymes. New pathways involving activated lysosomal steroid sulfatases link patient symptoms usually related inborn errors metabolism Additionally, new roles lysyl oxidase activation molecules necessary innate immune system, novel adapter that play ERGIC trafficking brain receptors proteins, are emerging. We here summarize current knowledge enzyme disease, with a focus on ATP7A-mediated metalation secretory pathway. By establishing mechanistic relationships between processes patients will not only increase understanding biology also allow identification an expanding pathways. This raise awareness rare symptoms, thus aid early diagnosis patients.

Language: Английский

Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: A comprehensive review DOI Creative Commons
Lina Schiffer, Lise Barnard, Elizabeth S. Baranowski

et al.

The Journal of Steroid Biochemistry and Molecular Biology, Journal Year: 2019, Volume and Issue: 194, P. 105439 - 105439

Published: July 27, 2019

Advances in technology have allowed for the sensitive, specific, and simultaneous quantitative profiling of steroid precursors, bioactive steroids inactive metabolites, facilitating comprehensive characterization serum urine metabolomes. The quantification panels is therefore gaining favor over single marker metabolites clinical research laboratories. However, although biochemical pathways biosynthesis metabolism hormones are now well defined, a gulf still exists between this knowledge its application to measured profiles. In review, we present an overview hormone by liver peripheral tissues, specifically highlighting linking differentiating A brief methodology used also provided.

Language: Английский

Citations

326
Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration DOI Creative Commons
Joana Revez, Tian Lin, Zhen Qiao

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: April 2, 2020

Abstract Vitamin D deficiency is a candidate risk factor for range of adverse health outcomes. In genome-wide association study 25 hydroxyvitamin (25OHD) concentration in 417,580 Europeans we identify 143 independent loci 112 1-Mb regions, providing insights into the physiology vitamin and implicating genes involved lipid lipoprotein metabolism, dermal tissue properties, sulphonation glucuronidation 25OHD. Mendelian randomization models find no robust evidence that 25OHD has causal effects on phenotypes (e.g. BMI, psychiatric disorders), but many have (direct or indirect) concentration, clarifying epidemiological relationship between status outcomes examined this study.

Language: Английский

Citations

307
Designing multi-targeted agents: An emerging anticancer drug discovery paradigm DOI

Rong-geng Fu,

Yuan Sun, Wenbing Sheng

et al.

European Journal of Medicinal Chemistry, Journal Year: 2017, Volume and Issue: 136, P. 195 - 211

Published: May 5, 2017

Language: Английский

Citations

196
Are we close to defining a metabolomic signature of human obesity? A systematic review of metabolomics studies DOI Creative Commons
Óscar Daniel Rangel-Huerta, Belén Pastor‐Villaescusa, Ángel Gil

et al.

Metabolomics, Journal Year: 2019, Volume and Issue: 15(6)

Published: June 1, 2019

Obesity is a disorder characterized by disproportionate increase in body weight relation to height, mainly due the accumulation of fat, and considered pandemic present century many international health institutions. It associated with several non-communicable chronic diseases, namely, metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), cancer. Metabolomics useful tool evaluate changes metabolites being overweight obesity at fluid cellular levels ascertain metabolically unhealthy obese individuals (MUHO) compared healthy (MHO).We aimed conduct systematic review (SR) human studies focused on identifying metabolomic signatures obesity-related alterations, such as inflammation or oxidative stress.We reviewed literature identify investigating metabolomics profile that were published up May 7th, 2019 SCOPUS PubMed through an SR. The quality reporting was evaluated using adapted QUADOMICS.Thirty-three articles included classified according four types approaches. (i) studying signature obesity, (ii) differential responses non-obese subjects dietary challenges (iii) used predict loss assess effects interventions profiles (iv) studied specific patterns compounds alterations humans.The SR provides state-of-the-art information about use approach understanding dynamics processes involved emphasizes related phenotypes.

Language: Английский

Citations

194
From Pregnancy to Preeclampsia: A Key Role for Estrogens DOI Open Access

Nadia Berkane,

Philippe Lière,

Jean‐Paul Oudinet

et al.

Endocrine Reviews, Journal Year: 2017, Volume and Issue: 38(2), P. 123 - 144

Published: March 3, 2017

Preeclampsia (PE) results in placental dysfunction and is one of the primary causes maternal fetal mortality morbidity. During pregnancy, estrogen produced primarily placenta by conversion androgen precursors originating from adrenal glands. These processes lead to increased plasma concentrations compared with levels nonpregnant women. Aberrant production estrogens could play a key role PE symptoms because they are exclusively promote angiogenesis vasodilation. Previous assessments synthesis during yielded conflicting results, possibly lack specificity assays. However, introduction reliable analytical protocols using liquid chromatography/mass spectrometry or gas spectrometry, more recent studies suggest marked decrease estradiol PE. The aim this review summarize current knowledge synthesis, regulation placenta, biological effects pregnancy Moreover, highlights links among occurrence PE, biosynthesis, angiogenic factors, cardiovascular risk factors. A close link between dysregulation might validate as biomarker but also reveal potential approach for prevention cure

Language: Английский

Citations

183
Intracrine androgen biosynthesis, metabolism and action revisited DOI Creative Commons
Lina Schiffer, Wiebke Arlt, Karl‐Heinz Storbeck

et al.

Molecular and Cellular Endocrinology, Journal Year: 2017, Volume and Issue: 465, P. 4 - 26

Published: Sept. 1, 2017

Androgens play an important role in metabolic homeostasis and reproductive health both men women. Androgen signalling is dependent on androgen receptor activation, mostly by testosterone 5α-dihydrotestosterone. However, the intracellular or intracrine activation of C

Language: Английский

Citations

180
Characterization of interactions of dietary cholesterol with the murine and human gut microbiome DOI Creative Commons
Henry H. Le,

Min-Ting Lee,

Kevin R. Besler

et al.

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(9), P. 1390 - 1403

Published: Aug. 18, 2022

Abstract Consumption of dietary lipids, such as cholesterol, modulates the gut microbiome with consequences for host health through production microbiome-derived metabolites. Despite implications metabolism, a limited number specific interactions diet-derived lipids have been characterized. This is partially because obtaining species-level resolution responsible taxa can be challenging and additional approaches are needed to identify health-relevant metabolites produced from cholesterol–microbiome interactions. Here we performed bio-orthogonal labelling sort sequence spectrometry, click chemistry based workflow, profile cholesterol-specific host–microbe Mice were exposed an alkyne-functionalized variant cholesterol 16S ribosomal RNA gene amplicon sequencing faecal samples identified cholesterol-interacting microbes genera Bacteroides , Bifidobacterium Enterococcus Parabacteroides . Shotgun metagenomic analysis provided enrichment bile acid-like sulfotransferase-like activities. Using untargeted metabolomics, that converted sulfate in -specific manner via enzyme BT_0416. monocolonized thetaiotaomicron lacking Bt_0416 showed altered compared wild-type mice, identifying previously uncharacterized microbiome-transformation mechanism microbiome-dependent contributions phenotype. Moreover, identification cholesterol-responsive sulfotransferase suggests diet-dependent mechanisms altering microbiome-specific metabolism. Overall, our work identifies numerous more precise microbiome-conscious regulation homeostasis.

Language: Английский

Citations

75
The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates DOI Creative Commons
Erkka Järvinen, Feng Deng, Wilma Kiander

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 13, 2022

Glucuronidation and sulfation are the most typical phase II metabolic reactions of drugs. The resulting glucuronide sulfate conjugates generally considered inactive safe. They may, however, be prominent drug-related material in circulation excreta humans. metabolites drugs typically have limited cell membrane permeability subsequently, their distribution excretion from human body requires transport proteins. Uptake transporters, such as organic anion transporters (OATs OATPs), mediate uptake into liver kidney, while efflux multidrug resistance proteins (MRPs) breast cancer protein (BCRP), expulsion bile, urine intestinal lumen. Understanding active conjugated drug is important for predicting fate a its safety efficacy. aim this review to compile understanding transporter-mediated disposition conjugates. We literature on hepatic, renal participating drugs, other xenobiotics endobiotics. In addition, we provide an update involvement metabolites. Finally, discuss interplay between intestine, kidneys well role conjugate toxicity, interactions, pharmacogenetics species differences.

Language: Английский

Citations

70
Novel mechanisms for DHEA action DOI Open Access
Russell A. Prough, Barbara J. Clark, Carolyn M. Klinge

et al.

Journal of Molecular Endocrinology, Journal Year: 2016, Volume and Issue: 56(3), P. R139 - R155

Published: Feb. 24, 2016

Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA), secreted by the adrenal cortex, gastrointestinal tract, gonads, and brain, its sulfated metabolite DHEA-S are most abundant endogeneous circulating steroid hormones. DHEA actions classically associated with age-related changes in cardiovascular tissues, female fertility, metabolism, neuronal/CNS functions. Early work on action focused metabolism to more potent sex hormones, testosterone estradiol, subsequent effect activation of androgen estrogen receptors. However, it is now clear that act directly as ligands for many hepatic nuclear receptors G-protein-coupled In addition, can function mediate acute cell signaling pathways. This review summarizes molecular mechanisms which acts cells animal models a focus 'novel' physiological modes action.

Language: Английский

Citations

145
A new dawn for androgens: Novel lessons from 11-oxygenated C19 steroids DOI
Elzette Pretorius, Wiebke Arlt, Karl‐Heinz Storbeck

et al.

Molecular and Cellular Endocrinology, Journal Year: 2016, Volume and Issue: 441, P. 76 - 85

Published: Aug. 10, 2016

Language: Английский

Citations

133