Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disturbances in energy homeostasis can result in obesity and other metabolic diseases. Here we report a metabolic pathway present in normal human skeletal muscle myoblasts that is activated by the small polyphenolic molecule kaempferol (KPF). Treatment with KPF leads to an approximately 30% increase in skeletal myocyte oxygen consumption. The mechanism involves a several-fold increase in cyclic AMP (cAMP) generation and protein kinase A activation, and the effect of KPF can be mimicked via treatment with dibutyryl cAMP. Microarray and real-time PCR studies identified a set of metabolically relevant genes influenced by KPF including peroxisome proliferator-activated receptor gamma coactivator-1alpha, carnitine palmitoyl transferase-1, mitochondrial transcription factor 1, citrate synthase, and uncoupling protein-3, although KPF itself is not a direct mitochondrial uncoupler. The cAMP-responsive gene for type 2 iodothyronine deiodinase (D2), an intracellular enzyme that activates thyroid hormone (T3) for the nucleus, is approximately threefold upregulated by KPF; furthermore, the activity half-life for D2 is dramatically and selectively increased as well. The net effect is an approximately 10-fold stimulation of D2 activity as measured in cell sonicates, with a concurrent increase of approximately 2.6-fold in the rate of T3 production, which persists even 24 h after KPF has been removed from the system. The effects of KPF on D2 are independent of sirtuin activation and only weakly reproduced by other small polyphenolic molecules such as quercetin and fisetin. These data document a novel mechanism by which a xenobiotic-activated pathway can regulate metabolically important genes as well as thyroid hormone activation and thus may influence metabolic control in humans.
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PMID:The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation. 1732 47

Juveniles of Solea solea were sampled during the spring season in three consecutive years at a marine site by the mouth of the Ebre river. The aim was to assess if the extractive works from the toxic load upstream the river could be reflected on the health status of the fish living at the immediate sea. The biomarkers selected for the in vivo field study are commonly used as indicators of chemical exposures. They include activities of energy metabolism: lactate dehydrogenase (LDH) and citrate synthase (CS); neurotoxicity: cholinesterases (ChE); xenobiotic metabolism: cytochrome P450 (CYP)-dependent: EROD and BFCOD, carboxylesterase (CbE), glutathione S-transferase (GST) and uridine diphosphate glucuronyltransferase (UDPGT); and oxidative stress parameters such as catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPX) as well as levels of lipid peroxidation (LPO). These biomarkers were mostly analysed in liver but also in gills and muscle depending on their particular tissue distribution and role. A complementary in vitro approach was also sought to see the capacity of common emerging contaminants (pharmaceuticals and personal care products; PPCPs) to interact with the liver microsomal detoxification system of the fish (EROD, BFCOD and CbE activities). The results indicated that in fish sampled in 2015 there was an enhancement in detoxification parameters (EROD, BFCOD and gill GR), muscular ChEs and gill CS, but a decrease in CbE activity and a marked oxidative stress situation (increased LPO and decreased CAT activity). Also, 4 out of the 10 PPCPs tested in vitro were able to interact with the CYP3A4 (BFCOD) enzymatic system while the lipid regulators simvastatin and fenofibrate inhibited CbE activity, as it occurs in higher vertebrates. The in vivo results support the use of a multibiomarker approach when assessing the disturbances due to chemical exposures, not only spatially but also over time, once the influence of other variables has been taken into consideration. The in vitro results highlight the importance of the CYP3A4 and CbE pathway in pharmaceutical metabolism, also in fish.
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PMID:The use of juvenile Solea solea as sentinel in the marine platform of the Ebre Delta: in vitro interaction of emerging contaminants with the liver detoxification system. 2735 7

Specimens of two endemic cyprinids, Squalius laietanus (Catalan chub) and Barbus meridionalis (Mediterranean barbel), were sampled from a reference site in a small stream of the Ripoll River (NW Mediterranean) outside of their reproductive season. Biomarkers involved in xenobiotic-mediated responses were individually contrasted in fish of both species and 17 perfluoroalkyl substances (PFASs) analysed in muscle to reveal bioaccumulation trends. The parameters were in muscle: cholinesterases, metabolic lactate dehydrogenase (LDH) and citrate synthase (CS); and in liver: cytochrome P450 dependent activities (EROD and BFCOD), carboxylesterase (CE), glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPX) and catalase (CAT). All markers are considered adaptive defence mechanism to face stress. Sensitivity to a model pesticide: dichlorvos was also contrasted in vitro in muscular acetylcholinesterase (AChE) and hepatic CE to reveal species sensitivity to neurotoxic chemicals. Enzymatic activities related to protective mechanisms such as butyrylcholinesterase (BuChE), CE and CAT were higher in chub whereas the antioxidant defences GR and GPX were higher in barbel. Aerobic CS was also higher in barbel while anaerobic LDH was so in chub. EROD activity did not differ between the two species but BFCOD activity was higher in barbel. Levels of PFAS were higher in barbel likely due to its benthic habitat. The in vitro tests revealed higher sensitivity to dichlorvos of muscular AChE in chub (lower IC50) which was probably compensated by a higher catalytic efficiency of CE. All these former biochemical particularities are discussed in terms of fish ecological performance in front of anthropogenic stressors.
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PMID:Biochemical aspects of susceptibility to stressors in two small cyprinids Squalius laietanus and Barbus meridionalis from the NW Mediterranean. 3317 Dec 99