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Environmental Pollution (Barking, Essex... Jun 2019Alpha-cypermethrin (Alpha-CP), an important pyrethroid pesticide, has been widely used for pest control in agriculture and parasite control in livestock farms. Thus,...
Alpha-cypermethrin (Alpha-CP), an important pyrethroid pesticide, has been widely used for pest control in agriculture and parasite control in livestock farms. Thus, alpha-CP is easily exposed to wild birds and poultry, which may pose a potential risk to birds. Alpha-CP and its metabolites have been detected in many environmental samples, including poultry and wild birds. We studied the distribution and metabolism of alpha-CP and its metabolites in embryo development and newborn chick. The results showed that metabolites were the main residual forms of alpha-CP in different stages of life and might increase the exposure risk of bird and its offspring. Metabolomics investigation of newborn chick exhibited that the metabolic profiles of chicks were disturbed, especially lipid metabolism. The concentrations of cis-DCCA and trans-DCCA were high in the first and second weeks of chick growth, indicating that chicks have limited ability to further metabolize and excrete cis-DCCA and trans-DCCA during the early stages of chicks. Toxicokinetics of alpha-CP in adult hens showed that alpha-CP was rapidly metabolized to acid metabolites, which could be further metabolized and excreted. The results about metabolism of alpha-CP in different stages of chicken indicate that the ability of the embryo and early chick to metabolize alpha-CP and its metabolites was the weakest. Therefore, it is of important significance to focus on evaluating the ecological risk of cypermethrin on birds at different stages of life cycle.
Topics: Agriculture; Animals; Chick Embryo; Chickens; Embryonic Development; Female; Insecticides; Pyrethrins; Toxicokinetics
PubMed: 30909131
DOI: 10.1016/j.envpol.2019.03.017 -
Trends in Microbiology Sep 2020Cells in assemblages differentiate and perform distinct roles. Though many pathways of differentiation are understood at the molecular level in multicellular eukaryotes,... (Review)
Review
Cells in assemblages differentiate and perform distinct roles. Though many pathways of differentiation are understood at the molecular level in multicellular eukaryotes, the elucidation of similar processes in bacterial assemblages is recent and ongoing. Here, we discuss examples of bacterial differentiation, focusing on cases in which distinct metabolisms coexist and those that exhibit cross-feeding, with one subpopulation producing substrates that are metabolized by a second subpopulation. We describe several studies of single-species systems, then segue to studies of multispecies metabolic heterogeneity and cross-feeding in the clinical setting. Many of the studies described exemplify the application of new techniques and modeling approaches that provide insights into metabolic interactions relevant for bacterial growth outside the laboratory.
Topics: Bacteria; Bacterial Physiological Phenomena; Biofilms; Drug Resistance, Bacterial; Metabolic Networks and Pathways; Microbial Interactions; Microfluidics
PubMed: 32781027
DOI: 10.1016/j.tim.2020.03.008 -
Current Opinion in Biotechnology Jun 2017New strategies for metabolic engineering of extremely thermophilic microorganisms to produce bio-based fuels and chemicals could leverage pathways and physiological... (Review)
Review
New strategies for metabolic engineering of extremely thermophilic microorganisms to produce bio-based fuels and chemicals could leverage pathways and physiological features resident in extreme thermophiles for improved outcomes. Furthermore, very recent advances in genetic tools for these microorganisms make it possible for them to serve as metabolic engineering hosts. Beyond providing a higher temperature alternative to mesophilic platforms, exploitation of strategic metabolic characteristics of high temperature microorganisms grants new opportunities for biotechnological products. This review considers recent developments in extreme thermophile biology as they relate to new horizons for energy biotechnology.
Topics: Archaea; Biotechnology; Carbon Dioxide; Chemoautotrophic Growth; Energy Metabolism; Hot Temperature; Lignin; Metabolic Engineering
PubMed: 28319854
DOI: 10.1016/j.copbio.2017.02.016 -
Bioresource Technology Jul 2023Recent advances in metabolic engineering have made cyanobacteria emerge as promising and attractive microorganisms for sustainable production, by exploiting their... (Review)
Review
Recent advances in metabolic engineering have made cyanobacteria emerge as promising and attractive microorganisms for sustainable production, by exploiting their natural capability for producing metabolites. The potential of metabolically engineered cyanobacterium would depend on its source-sink balance in the same way as other phototrophs. In cyanobacteria, the amount of light energy harvested (Source) is incompletely utilized by the cell to fix carbon (sink) resulting in wastage of the absorbed energy causing photoinhibition and cellular damage leading to lowered photosynthetic efficiency. Although regulatory pathways like photo-acclimation and photoprotective processes can be helpful unfortunately they limit the cell's metabolic capacity. This review describes approaches for source-sink balance and engineering heterologous metabolic sinks in cyanobacteria for enhanced photosynthetic efficiency. The advances for engineering additional metabolic pathways in cyanobacteria are also described which will provide a better understanding of the cyanobacterial source-sink balance and approaches for efficient cyanobacterial strains for valuable metabolites.
Topics: Metabolic Engineering; Cyanobacteria; Photosynthesis; Metabolic Networks and Pathways
PubMed: 36990331
DOI: 10.1016/j.biortech.2023.128974 -
Drug Metabolism Reviews Aug 2017Metabolism in the eye for any species, laboratory animals or human, is gaining rapid interest as pharmaceutical scientists aim to treat a wide range of so-called... (Review)
Review
Metabolism in the eye for any species, laboratory animals or human, is gaining rapid interest as pharmaceutical scientists aim to treat a wide range of so-called incurable ocular diseases. Over a period of decades, reports of metabolic activity toward various drugs and biochemical markers have emerged in select ocular tissues of animals and humans. Ocular cytochrome P450 (P450) enzymes and transporters have been recently reviewed. However, there is a dearth of collated information on non-P450 drug metabolizing enzymes in eyes of various preclinical species and humans in health and disease. In an effort to complement ocular P450s and transporters, which have been well reviewed in the literature, this review is aimed at presenting collective information on non-P450 oxidative, hydrolytic, and conjugative ocular drug metabolizing enzymes. Herein, we also present a list of xenobiotics or drugs that have been reported to be metabolized in the eye.
Topics: Animals; Cytochrome P-450 Enzyme System; Eye; Humans; Oxidation-Reduction; Xenobiotics
PubMed: 28438049
DOI: 10.1080/03602532.2017.1322609 -
PloS One 2016Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of...
Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome) in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs) also indicate geographic as well as age specific trends.
Topics: Adolescent; Adult; Age Factors; Aged; Bacteria; Child; Child, Preschool; Enzymes; Ethnicity; Female; Gastrointestinal Microbiome; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Humans; Inactivation, Metabolic; Infant; Infant, Newborn; Male; Metabolic Networks and Pathways; Metagenome; Middle Aged; Xenobiotics
PubMed: 27695034
DOI: 10.1371/journal.pone.0163099 -
Drug Metabolism Reviews May 2015This article reviews in vitro metabolic activities [including Michaelis constants (Km), maximal velocities (Vmax) and Vmax/Km] and drug-steroid interactions [such as... (Review)
Review
This article reviews in vitro metabolic activities [including Michaelis constants (Km), maximal velocities (Vmax) and Vmax/Km] and drug-steroid interactions [such as induction and cooperativity (activation)] of cytochromes P450 (P450 or CYP) in human tissues, including liver and adrenal gland, for 14 kinds of endogenous steroid compounds, including allopregnanolone, cholesterol, cortisol, cortisone, dehydroepiandrosterone, estradiol, estrone, pregnenolone, progesterone, testosterone and bile acids (cholic acid). First, we considered the drug-metabolizing P450s. 6β-Hydroxylation of many steroids, including cortisol, cortisone, progesterone and testosterone, was catalyzed primarily by CYP3A4. CYP1A2 and CYP3A4, respectively, are likely the major hepatic enzymes responsible for 2-/4-hydroxylation and 16α-hydroxylation of estradiol and estrone, steroids that can contribute to breast cancer risk. In contrast, CYP1A1 and CYP1B1 predominantly metabolized estrone and estradiol to 2- and 4-catechol estrogens, which are endogenous ultimate carcinogens if formed in the breast. Some metabolic activities of CYP3A4, including dehydroepiandrosterone 7β-/16α-hydroxylation, estrone 2-hydroxylation and testosterone 6β-hydroxylation, were higher than those for polymorphically expressed CYP3A5. Next, we considered typical steroidogenic P450s. CYP17A1, CYP19A1 and CYP27A1 catalyzed steroid synthesis, including hydroxylation at 17α, 19 and 27 positions, respectively. However, it was difficult to predict which hepatic drug-metabolizing P450 or steroidogenic P450 will be mainly responsible for metabolizing each steroid hormone in vivo based on these results. Further research is required on the metabolism of steroid hormones by various P450s and on prediction of their relative contributions to in vivo metabolism. The findings collected here provide fundamental and useful information on the metabolism of steroid compounds.
Topics: Adrenal Glands; Cholesterol; Cytochrome P-450 Enzyme System; Estradiol; Humans; Hydroxylation; In Vitro Techniques; Liver; Testosterone
PubMed: 25678418
DOI: 10.3109/03602532.2015.1011658 -
Advances in Experimental Medicine and... 2019The liver plays a capital role in the control of whole body energy homeostasis through the metabolization of dietary carbohydrates and lipids. However, under excess... (Review)
Review
The liver plays a capital role in the control of whole body energy homeostasis through the metabolization of dietary carbohydrates and lipids. However, under excess macronutrient uptake, those pathways overcharge nucleus-to-endoplasmic reticulum (ER) traffic pathways, leading to luminal overload of unfolded proteins which activates a series of adaptive signaling pathways known as unfolded protein response (UPR). The UPR is a central network mechanism for cellular stress adaptation, however far from a global nonspecific all-or-nothing response. Such a complex signaling network is able to display considerable specificity of responses, with activation of specific signaling branches trimmed for distinct types of stimuli. This makes the UPR a fundamental mechanism underlying metabolic processes and diseases, especially those related to lipid and carbohydrate metabolism. Thus, for a better understanding of the role of UPR on the physiopathology of lipid metabolism disorders, the concepts discussed along this chapter will demonstrate how several metabolic derangements activate UPR components and, in turn, how UPR triggers several metabolic adaptations through its component signaling proteins. This dual role of UPR on lipid metabolism will certainly foment the pursuit of an answer for the question: is UPR cause or consequence of lipid and lipoprotein metabolism disturbances?
Topics: Endoplasmic Reticulum; Lipid Metabolism; Lipoproteins; Signal Transduction; Unfolded Protein Response
PubMed: 31140172
DOI: 10.1007/978-3-030-11488-6_5 -
Drug Metabolism and Disposition: the... Aug 2016The drug-metabolizing enzymes that contribute to the metabolism or bioactivation of a drug play a crucial role in defining the absorption, distribution, metabolism, and...
The drug-metabolizing enzymes that contribute to the metabolism or bioactivation of a drug play a crucial role in defining the absorption, distribution, metabolism, and excretion properties of that drug. Although the overall effect of the cytochrome P450 (P450) family of drug-metabolizing enzymes in this capacity cannot be understated, advancements in the field of non-P450-mediated metabolism have garnered increasing attention in recent years. This is perhaps a direct result of our ability to systematically avoid P450 liabilities by introducing chemical moieties that are not susceptible to P450 metabolism but, as a result, may introduce key pharmacophores for other drug-metabolizing enzymes. Furthermore, the effects of both P450 and non-P450 metabolism at a drug's site of therapeutic action have also been subject to increased scrutiny. To this end, this Special Section on Emerging Novel Enzyme Pathways in Drug Metabolism will highlight a number of advancements that have recently been reported. The included articles support the important role of non-P450 enzymes in the clearance pathways of U.S. Food and Drug Administration-approved drugs over the past 10 years. Specific examples will detail recent reports of aldehyde oxidase, flavin-containing monooxygenase, and other non-P450 pathways that contribute to the metabolic, pharmacokinetic, or pharmacodynamic properties of xenobiotic compounds. Collectively, this series of articles provides additional support for the role of non-P450-mediated metabolic pathways that contribute to the absorption, distribution, metabolism, and excretion properties of current xenobiotics.
Topics: Activation, Metabolic; Animals; Cytochrome P-450 Enzyme System; Glucuronosyltransferase; Humans; Inactivation, Metabolic; Oxidation-Reduction; Oxidoreductases; Substrate Specificity; Sulfotransferases; Xenobiotics
PubMed: 27298339
DOI: 10.1124/dmd.116.071753 -
Biochimica Et Biophysica Acta.... Jan 2017Mitochondria and fatty acids are tightly connected to a multiplicity of cellular processes that go far beyond mitochondrial fatty acid metabolism. In line with this... (Review)
Review
Mitochondria and fatty acids are tightly connected to a multiplicity of cellular processes that go far beyond mitochondrial fatty acid metabolism. In line with this view, there is hardly any common metabolic disorder that is not associated with disturbed mitochondrial lipid handling. Among other aspects of mitochondrial lipid metabolism, apparently all eukaryotes are capable of carrying out de novo fatty acid synthesis (FAS) in this cellular compartment in an acyl carrier protein (ACP)-dependent manner. The dual localization of FAS in eukaryotic cells raises the questions why eukaryotes have maintained the FAS in mitochondria in addition to the "classic" cytoplasmic FAS and what the products are that cannot be substituted by delivery of fatty acids of extramitochondrial origin. The current evidence indicates that mitochondrial FAS is essential for cellular respiration and mitochondrial biogenesis. Although both β-oxidation and FAS utilize thioester chemistry, CoA acts as acyl-group carrier in the breakdown pathway whereas ACP assumes this role in the synthetic direction. This arrangement metabolically separates these two pathways running towards opposite directions and prevents futile cycling. A role of this pathway in mitochondrial metabolic sensing has recently been proposed. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.
Topics: Acyl Carrier Protein; Animals; Cell Respiration; Fatty Acids; Humans; Lipid Metabolism; Lipogenesis; Mitochondria; Oxidation-Reduction
PubMed: 27553474
DOI: 10.1016/j.bbalip.2016.08.011