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31.
Aikaterini Dimou Vasilis Tsimihodimos Eleni Bairaktari 《International journal of molecular sciences》2022,23(7)
Branched chain amino acids (BCAAs), leucine, isoleucine and valine, are essential amino acids widely studied for their crucial role in the regulation of protein synthesis mainly through the activation of the mTOR signaling pathway and their emerging recognition as players in the regulation of various physiological and metabolic processes, such as glucose homeostasis. BCAA supplementation is primarily used as a beneficial nutritional intervention in chronic liver and kidney disease as well as in muscle wasting disorders. However, downregulated/upregulated plasma BCAAs and their defective catabolism in various tissues, mainly due to altered enzymatic activity of the first two enzymes in their catabolic pathway, BCAA aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD), have been investigated in many nutritional and disease states. The current review focused on the underlying mechanisms of altered BCAA catabolism and its contribution to the pathogenesis of a numerous pathological conditions such as diabetes, heart failure and cancer. In addition, we summarize findings that indicate that the recovery of the dysregulated BCAA catabolism may be associated with an improved outcome and the prevention of serious disease complications. 相似文献
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Katharina B. Kuentzel Ivan Bradi&#x; Alena Akhmetshina Melanie Korbelius Silvia Rainer Dagmar Kolb Martin Gauster Nemanja Vuji&#x; Dagmar Kratky 《International journal of molecular sciences》2021,22(19)
Cholesterol and fatty acids are essential lipids that are critical for membrane biosynthesis and fetal organ development. Cholesteryl esters (CE) are degraded by hormone-sensitive lipase (HSL) in the cytosol and by lysosomal acid lipase (LAL) in the lysosome. Impaired LAL or HSL activity causes rare pathologies in humans, with HSL deficiency presenting less severe clinical manifestations. The infantile form of LAL deficiency, a lysosomal lipid storage disorder, leads to premature death. However, the importance of defective lysosomal CE degradation and its consequences during early life are incompletely understood. We therefore investigated how defective CE catabolism affects fetus and infant maturation using Lal and Hsl knockout (-/-) mouse models. This study demonstrates that defective lysosomal but not neutral lipolysis alters placental and fetal cholesterol homeostasis and exhibits an initial disease pathology already in utero as Lal-/- fetuses accumulate hepatic lysosomal lipids. Immediately after birth, LAL deficiency exacerbates with massive hepatic lysosomal lipid accumulation, which continues to worsen into young adulthood. Our data highlight the crucial role of LAL during early development, with the first weeks after birth being critical for aggravating LAL deficiency. 相似文献
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Elias K. Zegeye Natalie C. Sadler Gerard X. Lomas Isaac K. Attah Dr. Janet K. Jansson Dr. Kirsten S. Hofmockel Dr. Christopher R. Anderton Dr. Aaron T. Wright 《Chembiochem : a European journal of chemical biology》2021,22(4):717-723
The microbial catabolism of chitin, an abundant and ubiquitous environmental organic polymer, is a fundamental cog in terrestrial and aquatic carbon and nitrogen cycles. Despite the importance of this critical bio-geochemical function, there is a limited understanding of the synergy between the various hydrolytic and accessory enzymes involved in chitin catabolism. To address this deficit, we synthesized activity-based probes (ABPs) designed to target active chitinolytic enzymes by modifying the chitin subunits N-acetyl glucosamine and chitotriose. The ABPs were used to determine the active complement of chitinolytic enzymes produced over time by the soil bacterium Cellvibrio japonicus treated with various C substrates. We demonstrate the utility of these ABPs in determining the synergy between various enzymes involved in chitin catabolism. The strategy can be used to gain molecular-level insights that can be used to better understand microbial roles in soil bio-geochemical cycling in the face of a changing climate. 相似文献
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Chia-Ming Chang Yao-Feng Li Hsin-Chung Lin Kai-Hsi Lu Tzu-Wei Lin Li-Chun Liu Kuo-Min Su Cheng-Chang Chang 《International journal of molecular sciences》2021,22(8)
The pathogenesis and molecular mechanisms of ovarian low malignant potential (LMP) tumors or borderline ovarian tumors (BOTs) have not been fully elucidated to date. Surgery remains the cornerstone of treatment for this disease, and diagnosis is mainly made by histopathology to date. However, there is no integrated analysis investigating the tumorigenesis of BOTs with open experimental data. Therefore, we first utilized a functionome-based speculative model from the aggregated obtainable datasets to explore the expression profiling data among all BOTs and two major subtypes of BOTs, serous BOTs (SBOTs) and mucinous BOTs (MBOTs), by analyzing the functional regularity patterns and clustering the separate gene sets. We next prospected and assembled the association between these targeted biomolecular functions and their related genes. Our research found that BOTs can be accurately recognized by gene expression profiles by means of integrative polygenic analytics among all BOTs, SBOTs, and MBOTs; the results exhibited the top 41 common dysregulated biomolecular functions, which were sorted into four major categories: immune and inflammatory response-related functions, cell membrane- and transporter-related functions, cell cycle- and signaling-related functions, and cell metabolism-related functions, which were the key elements involved in its pathogenesis. In contrast to previous research, we identified 19 representative genes from the above classified categories (IL6, CCR2 for immune and inflammatory response-related functions; IFNG, ATP1B1, GAS6, and PSEN1 for cell membrane- and transporter-related functions; CTNNB1, GATA3, and IL1B for cell cycle- and signaling-related functions; and AKT1, SIRT1, IL4, PDGFB, MAPK3, SRC, TWIST1, TGFB1, ADIPOQ, and PPARGC1A for cell metabolism-related functions) that were relevant in the cause and development of BOTs. We also noticed that a dysfunctional pathway of galactose catabolism had taken place among all BOTs, SBOTs, and MBOTs from the analyzed gene set databases of canonical pathways. With the help of immunostaining, we verified significantly higher performance of interleukin 6 (IL6) and galactose-1-phosphate uridylyltransferase (GALT) among BOTs than the controls. In conclusion, a bioinformatic platform of gene-set integrative molecular functionomes and biophysiological pathways was constructed in this study to interpret the complicated pathogenic pathways of BOTs, and these important findings demonstrated the dysregulated immunological functionome and dysfunctional metabolic pathway as potential roles during the tumorigenesis of BOTs and may be helpful for the diagnosis and therapy of BOTs in the future. 相似文献
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Vincent Chochois Laure Constans David Dauvillée Audrey Beyly Mélanie Solivérès Steven Ball Gilles Peltier Laurent Cournac 《International Journal of Hydrogen Energy》2010
Sulfur deprivation, which is considered as an efficient way to trigger long-term hydrogen photoproduction in unicellular green algae has two major effects: a decrease in PSII which allows anaerobiosis to be reached and carbohydrate (starch) storage. Starch metabolism has been proposed as one of the major factors of hydrogen production, particularly during the PSII-independent (or indirect) pathway. While starch biosynthesis has been characterized in the green alga Chlamydomonas reinhardtii, little remains known concerning starch degradation. In order to gain a better understanding of starch catabolism pathways and identify those steps likely to limit the starch-dependent hydrogen production, we have designed a genetic screening procedure aimed at isolating mutants of the green alga C. reinhardtii affected in starch mobilization. Using two different screening protocols, the first one based on aerobic starch degradation in the dark and the second one on anaerobic starch degradation in the light, eighteen mutants were isolated among a library of 15,000 insertion mutants, eight (std1-8) with the first screen and ten (sda1-10) with the second. Most of the mutant strains isolated in this study showed a reduction or a delay in the PSII-independent hydrogen production. Further characterization of these mutants should allow the identification of molecular determinants of starch-dependent hydrogen production and supply targets for future biotechnological improvements. 相似文献
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Background and Aims: The majority of the acidity of a grapevine ( Vitis vinifera L.) berry is a result of the accumulation of l -tartaric (TA) and l -malic acids (MA). TA is synthesised from l -ascorbic acid (Asc, vitamin C), the metabolism of which is poorly characterised in grapevines. In a distinct pathway, oxalic acid (OA) is also formed from Asc degradation. The aim of this study was to develop a single method whereby the distribution of Asc and its catabolites from fruit and vegetative sources could be determined.
Methods and Results: Effective recoveries of total Asc, TA, OA and MA were achieved with this extraction method, while chromatographic separation was accomplished with reversed-phase high-performance liquid chromatography (RP-HPLC). These results demonstrate that Asc and its catabolites TA and OA rapidly accumulate in immature berries, and that the Asc to dehydroascorbate ratio increases with berry maturity.
Conclusions: A method for the simultaneous analysis of Asc, TA, OA and MA in fruits is provided; moreover, we have demonstrated its use to study their distribution in fruits, rachis, leaves and roots.
Significance of the Study: This method enables accurate monitoring of the accumulation of Asc, permitting further research towards understanding acid metabolism during berry ripening. 相似文献
Methods and Results: Effective recoveries of total Asc, TA, OA and MA were achieved with this extraction method, while chromatographic separation was accomplished with reversed-phase high-performance liquid chromatography (RP-HPLC). These results demonstrate that Asc and its catabolites TA and OA rapidly accumulate in immature berries, and that the Asc to dehydroascorbate ratio increases with berry maturity.
Conclusions: A method for the simultaneous analysis of Asc, TA, OA and MA in fruits is provided; moreover, we have demonstrated its use to study their distribution in fruits, rachis, leaves and roots.
Significance of the Study: This method enables accurate monitoring of the accumulation of Asc, permitting further research towards understanding acid metabolism during berry ripening. 相似文献
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Purine salvage is a complex pathway allowing a correct balance between adenylic and guanylic derivatives. In this paper, we show that GUD1 (YDL238c) encodes guanine deaminase, a catabolic enzyme producing xanthine and ammonia from guanine. Importantly, Gud1p activity was higher during post-diauxic growth, suggesting that a decrease of the guanylic nucleotide pool could be required when cells shift from proliferation to quiescence. 相似文献
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In this study, the volatile aroma profiles of a variety of economically important cheeses for the Turkish dairy sector were characterized. A total of 75 samples belonging to 11 Turkish cheese varieties, including Civil, Canak, Dil, Divle Tulum, Ezine, Hellim, Malatya, Mihalic, Orgu, Urfa, and Van Otlu, were comparatively studied for their volatile profiles. One hundred and twelve volatile compounds were identified in the cheeses by solid-phase microextraction combined with gas chromatography-mass spectrometry and the results are discussed based on their chemical classes (31 esters, 7 acids, 18 ketones, 3 aldehydes, 24 alcohols, 10 terpenes, and 19 miscellaneous compounds). Esters, ketones, and alcohols were the most abundant classes identified and were highly dependent on the variety of cheese. Principal component analysis was applied to aid the interpretation of the gas chromatography-mass spectrometry data and to distinguish the cheeses. Divle Tulum cheese had high levels of aldehydes, ketones, and alcohols and separated from all the other cheeses, and the cheeses including Dil, Hellim, Malatya, Orgu, and Urfa grouped together. The last group of cheeses had low levels of volatiles stemming probably from the restricting effect of scalding or cooking that are employed in the manufacture of these cheeses and on the biochemical and/or microbial activity. Civil, Ezine, and Mihalic cheeses had somewhat different aroma profiles, but they were closely located near the cheeses including Dil, Urfa, Orgu, etc. The results suggest that each variety of cheese had different volatiles profile and that the manufacturing technique as well as ripening conditions of the cheeses played a major role on the individual volatile profiles. 相似文献