Metabolites最新文献_第9页

Branched-Chain Amino Acids, Alanine, and Thyroid Function: A Cross-Sectional, Nuclear Magnetic Resonance (NMR)-Based Approach from ELSA-Brasil 支链氨基酸、丙氨酸与甲状腺功能：基于横截面核磁共振 (NMR) 的 ELSA-Brasil 方法

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-06 DOI: 10.3390/metabo14080437

Carolina Castro Porto Silva Janovsky, Vandrize Meneghini, William Tebar, Joao Roberto Maciel Martins, José Augusto Sgarbi, Patrícia de Fatima dos Santos Teixeira, Steven R. Jones, Michael J. Blaha, Peter P. Toth, Paulo A. Lotufo, Marcio S. Bittencourt, Raul D. Santos, Itamar S. Santos, Layal Chaker, Isabela M. Bensenor

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs—leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson’s coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism.

尽管必需氨基酸和非必需氨基酸具有共同的代谢作用，但甲状腺功能与这两种氨基酸之间的关系还没有得到充分研究。因此，我们的目的是评估甲状腺功能与普通人群中支链氨基酸（BCAA，即亮氨酸、异亮氨酸和缬氨酸）和丙氨酸水平的关系。我们利用了 ELSA-Brasil 圣保罗研究中心的数据，这是一项基于人群的纵向队列研究。甲状腺参数包括促甲状腺激素（TSH）、游离 T4 和游离 T3 水平以及 FT4:FT3 比率。在全自动 NMR 平台上对 BCAAs 和丙氨酸进行了分析。本次分析包括甲状腺功能正常的参与者以及亚临床甲状腺功能亢进和甲状腺功能减退的参与者。我们使用皮尔逊系数来量化甲状腺相关参数与氨基酸之间的相关性。我们使用线性回归模型来分析甲状腺参数是否与 BCAAs 和丙氨酸水平相关。本研究共纳入 4098 名参与者（51.3 ± 9.0 岁，51.5% 为女性）。在调整最多的模型中，较高的 TSH 水平与较高的丙氨酸水平相关，FT4 水平与异亮氨酸水平成反比，FT3 水平与缬氨酸和亮氨酸呈统计学意义上的正相关，T3：T4 比值与所有氨基酸呈正相关。我们观察到，在所有模型中，亚临床甲状腺机能减退都与异亮氨酸和丙氨酸水平呈正相关，即使经过充分调整也是如此。我们的研究结果突显了亚临床甲状腺机能减退和甲状腺相关参数（包括促甲状腺激素、游离 T4、游离 T3 和 FT4:FT3 比值）与 BCAAs 和丙氨酸的关系。还需要进一步的研究来探索这种关联的机制。这些见解有助于我们了解甲状腺相关参数对 BCAA 和丙氨酸代谢的影响。

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引用次数: 0

Deciphering Blood Flow Restriction Training to Aid Lipid Lowering in Obese College Students through Untargeted Metabolomics. 通过非靶向代谢组学破解限制血流量训练对肥胖大学生降脂的帮助

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-05 DOI: 10.3390/metabo14080433

Xianyou Cui, Sidorenko Tatiana Anatolevna, Yu Wang

(1) Objective: The aim of this study was to observe the lipid-lowering effects of blood flow restriction training (BFR) combined with moderate-intensity continuous training (MICT) in obese college students by observing lipid-lowering hormones and untargeted metabolomics. (2) Methods: In this study, 14 obese college students were convened into three groups-MICT, MICT+BFR, and high-intensity interval training (HIIT)-for a crossover experiment. Blood was drawn before and after exercise for the analysis of lipolytic agents and untargeted metabolomics. The study used a paired t-test and ANOVA for statistical analyses. (3) Results: The lipolytic agent results showed that MICT+BFR was superior to the other two groups in terms of two agents (p = 0.000 and p = 0.003), namely, GH and IL-6 (difference between before and after testing: 10,986.51 ± 5601.84 and 2.42 ± 2.49, respectively), and HIIT was superior to the other two groups in terms of one agent (p = 0.000), i.e., EPI (22.81 ± 16.12). No advantage was observed for MICT. The metabolomics results showed that, compared to MICT, MICT+BFR was associated with the upregulated expression of xanthine, succinate, lactate, N-lactoylphenylalanine, citrate, ureido acid, and myristic acid after exercise, with the possibility of the involvement of the citric acid cycle, alanine, aspartic acid, glutamate metabolism, butyric acid metabolism, and the histidylate metabolism pathway. (4) Conclusions: The superior lipid-lowering effect of MICT+BFR over MICT in a group of obese college students may be due to the stronger activation of GH and IL-6 agents, with the citric acid cycle and alanine, aspartate, and glutamate metabolic pathways being associated with this type of exercise.

(1）目的：本研究旨在通过观察降脂激素和非靶向代谢组学，观察血流限制训练（BFR）联合中等强度持续训练（MICT）对肥胖大学生的降脂作用。(2）方法：本研究将 14 名肥胖大学生分为三组--MICT、MICT+BFR 和高强度间歇训练（HIIT）--进行交叉实验。研究人员在运动前后抽取血液，用于分析脂肪分解因子和非靶向代谢组学。研究采用配对 t 检验和方差分析进行统计分析。(3）结果：溶脂剂结果显示，MICT+BFR 在两种溶脂剂方面优于其他两组（P = 0.000 和 P = 0.003），即 GH 和 IL-6（测试前后的差异：HIIT在一种药物方面优于其他两组（p = 0.000），即 EPI（22.81 ± 16.12）。MICT 没有优势。代谢组学结果显示，与 MICT 相比，MICT+BFR 与运动后黄嘌呤、琥珀酸、乳酸、N-乳酰苯丙氨酸、柠檬酸、脲酸和肉豆蔻酸的表达上调有关，可能涉及柠檬酸循环、丙氨酸、天冬氨酸、谷氨酸代谢、丁酸代谢和组氨酸代谢途径。(4）结论：在一组肥胖大学生中，MICT+BFR 的降脂效果优于 MICT，这可能是由于 GH 和 IL-6 的激活作用更强，柠檬酸循环、丙氨酸、天冬氨酸和谷氨酸代谢途径与这种类型的运动有关。

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引用次数: 0

Characterizing Growth-Retarded Japanese Eels (Anguilla japonica): Insights into Metabolic and Appetite Regulation. 生长受阻的日本鳗鲡的特征：新陈代谢和食欲调节的启示

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-05 DOI: 10.3390/metabo14080432

Xiangbiao Zeng, Jingwei Liu, Yiwen Chen, Huan Han, Yanhe Liu, Bin Xie, Tianwei Jiang, Chris Kong-Chu Wong, Kang Li, Liping Liu

During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel (NGE) under the same rearing conditions. The results showed that growth hormone (gh) mRNA expression in GREs was considerably lower than NGEs. The levels of total protein (TP), total cholesterol (T-CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood ammonia (BA), blood urea nitrogen (BUN), and alkaline phosphatase (ALP) in GREs were significantly lower than in NGEs. Conversely, levels of glucose (GLU), alanine aminotransferase (ALT), and aspartate transaminase (AST) were higher in GREs. The activities of SOD, CAT, and T-AOC levels were also significantly lower in GREs, as were the activities of glucose-related enzymes including hexokinase (HK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PASE). Additionally, orexigenic genes (npy and ghrelin) were dramatically downregulated, whereas anorexigenic genes (crh and pyy) were significantly upregulated in GREs. These findings suggested that variances in growth hormone, metabolic activities, and appetite level could be associated with the different growth rates of A. japonica. The present research not only revealed the characteristics of the growth, metabolism, and appetite of GREs but also offered new perspectives into the substantial growth discrepancies in A. japonica, providing novel ideas for enhancing fish growth.

在实地调查和养殖过程中，发现鳗鲡的生长差异很大。然而，潜在的原因尚不清楚。本研究探讨了在相同饲养条件下，生长迟缓鳗鲡（GRE）与正常生长鳗鲡（NGE）在消化能力、代谢水平以及食欲相关基因转录组谱方面的差异。结果表明，生长迟缓鳗鱼的生长激素（gh）mRNA表达量明显低于正常生长鳗鱼。鳗鲡的总蛋白（TP）、总胆固醇（T-CHO）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、血氨（BA）、血尿素氮（BUN）和碱性磷酸酶（ALP）水平明显低于正常生长鳗鲡。相反，GREs 的葡萄糖（GLU）、丙氨酸氨基转移酶（ALT）和天门冬氨酸转氨酶（AST）水平较高。在 GREs 中，SOD、CAT 和 T-AOC 的活性也明显降低，与葡萄糖相关的酶，包括己酮激酶（HK）、丙酮酸激酶（PK）、磷酸烯醇丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G6PASE）的活性也明显降低。此外，GREs 中的促厌基因（npy 和胃泌素）显著下调，而促厌基因（crh 和 pyy）则显著上调。这些发现表明，生长激素、代谢活动和食欲水平的差异可能与粳稻不同的生长速度有关。本研究不仅揭示了大菱鲆的生长、代谢和食欲特点，而且为了解大菱鲆的生长差异提供了新的视角，为促进鱼类生长提供了新的思路。

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引用次数: 0

Evaluation of Unsaponifiable Fraction of Avocado Oil on Liver and Kidney Mitochondrial Function in Rats Fed a High-Fat and High-Carbohydrate Diet 评估牛油果油的不皂化馏分对高脂肪和高碳水化合物饮食大鼠肝脏和肾脏线粒体功能的影响

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-04 DOI: 10.3390/metabo14080431

Marcela González-Montoya, Manuel Alejandro Vargas-Vargas, Olin Torres-Isidro, Claudia Isabel García-Berumen, María Guadalupe Cuiniche-Méndez, Alfredo Saavedra-Molina, Julio Cesar Ontiveros-Rodríguez, Hugo A. García-Gutiérrez, Elizabeth Calderón-Cortés, Christian Cortés-Rojo

High-fat and high-carbohydrate (HF-HC) diets induce metabolic syndrome via mitochondrial dysfunction and oxidative stress. We have previously shown that this may be prevented by avocado oil, a source of bioactive molecules with antioxidant properties. However, it is unknown if these effects are mediated by the unsaponifiable fraction of avocado oil (UFAO). Thus, we tested if this fraction improves glucose metabolism, bioenergetics and oxidative stress in mitochondria from the kidney and liver of rats fed an HF-HC diet. We found that 12 weeks of an HF-HC diet impaired glucose utilization and increased insulin resistance, which was prevented by UFAO administration. The HF-HC diet decreased respiration, membrane potential and electron transport chain (ETC) function in liver and kidney mitochondria. These mitochondrial dysfunctions were prevented by UFAO intake. Unexpectedly, UFAO increased ROS levels in the mitochondria of control animals and did not decrease them in rats with an HF-HC diet; however, UFAO protects liver and kidney mitochondria from iron-induced oxidative stress. These findings suggest that impairments in glucose metabolism and mitochondrial function by an HF-HC diet may be prevented by UFAO, without decreasing ROS generation but protecting mitochondria from oxidative damage.

高脂肪和高碳水化合物（HF-HC）饮食会通过线粒体功能障碍和氧化应激诱发代谢综合征。我们之前已经证明，牛油果油可以防止这种情况的发生，因为牛油果油是一种具有抗氧化特性的生物活性分子的来源。然而，这些效果是否由鳄梨油中的非皂化物部分（UFAO）介导尚不清楚。因此，我们测试了这种馏分是否能改善高密度脂蛋白胆固醇饮食大鼠肾脏和肝脏线粒体的葡萄糖代谢、生物能和氧化应激。我们发现，12 周的高密度脂蛋白胆固醇饮食会损害葡萄糖的利用并增加胰岛素抵抗，而服用 UFAO 则可防止这种情况。高密度脂蛋白胆固醇饮食降低了肝脏和肾脏线粒体的呼吸、膜电位和电子传递链（ETC）功能。摄入 UFAO 可防止这些线粒体功能障碍。意想不到的是，UFAO 增加了对照组动物线粒体中的 ROS 水平，但并没有降低高密度脂蛋白胆固醇饮食大鼠线粒体中的 ROS 水平；不过，UFAO 保护肝脏和肾脏线粒体免受铁诱导的氧化应激。这些研究结果表明，UFAO 可以防止高密度脂蛋白胆固醇饮食对葡萄糖代谢和线粒体功能的损害，它不会减少 ROS 的产生，但能保护线粒体免受氧化损伤。

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引用次数: 0

Unraveling Protein-Metabolite Interactions in Precision Nutrition: A Case Study of Blueberry-Derived Metabolites Using Advanced Computational Methods 揭示精准营养中蛋白质与代谢物的相互作用：使用先进计算方法的蓝莓衍生代谢物案例研究

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-03 DOI: 10.3390/metabo14080430

Dipendra Bhandari, Kiran Kumar Adepu, Andriy Anishkin, Colin D. Kay, Erin E. Young, Kyle M. Baumbauer, Anuradha Ghosh, Sree V. Chintapalli

Metabolomics, the study of small-molecule metabolites within biological systems, has become a potent instrument for understanding cellular processes. Despite its profound insights into health, disease, and drug development, identifying the protein partners for metabolites, especially dietary phytochemicals, remains challenging. In the present study, we introduced an innovative in silico, structure-based target prediction approach to efficiently predict protein targets for metabolites. We analyzed 27 blood serum metabolites from nutrition intervention studies’ blueberry-rich diets, known for their health benefits, yet with elusive mechanisms of action. Our findings reveal that blueberry-derived metabolites predominantly interact with Carbonic Anhydrase (CA) family proteins, which are crucial in acid-base regulation, respiration, fluid balance, bone metabolism, neurotransmission, and specific aspects of cellular metabolism. Molecular docking showed that these metabolites bind to a common pocket on CA proteins, with binding energies ranging from −5.0 kcal/mol to −9.0 kcal/mol. Further molecular dynamics (MD) simulations confirmed the stable binding of metabolites near the Zn binding site, consistent with known compound interactions. These results highlight the potential health benefits of blueberry metabolites through interaction with CA proteins.

代谢组学是对生物系统内小分子代谢物的研究，已成为了解细胞过程的有力工具。尽管代谢组学对健康、疾病和药物开发有着深刻的见解，但识别代谢物（尤其是膳食植物化学物质）的蛋白质伙伴仍具有挑战性。在本研究中，我们引入了一种创新的基于结构的硅学目标预测方法，以有效预测代谢物的蛋白质目标。我们分析了营养干预研究中 27 种血清代谢物，这些代谢物来自富含蓝莓的膳食，其健康益处众所周知，但作用机制却难以捉摸。我们的研究结果表明，蓝莓提取的代谢物主要与碳酸酐酶（CA）家族蛋白相互作用，这些蛋白在酸碱调节、呼吸、体液平衡、骨代谢、神经传递和细胞代谢的特定方面起着至关重要的作用。分子对接显示，这些代谢物与 CA 蛋白上的一个共同口袋结合，结合能从 -5.0 kcal/mol 到 -9.0 kcal/mol。进一步的分子动力学（MD）模拟证实，代谢物在锌结合位点附近稳定结合，与已知的化合物相互作用一致。这些结果突显了蓝莓代谢物通过与 CA 蛋白相互作用而对健康产生的潜在益处。

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引用次数: 0

Electrochemical Probing of Human Liver Subcellular S9 Fractions for Drug Metabolite Synthesis 用于药物代谢物合成的人肝脏亚细胞 S9 馏分电化学探针

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-03 DOI: 10.3390/metabo14080429

Daphne Medina, Bhavana Omanakuttan, Ricky Nguyen, Eman Alwarsh, Charuksha Walgama

Human liver subcellular fractions, including liver microsomes (HLM), liver cytosol fractions, and S9 fractions, are extensively utilized in in vitro assays to predict liver metabolism. The S9 fractions are supernatants of human liver homogenates that contain both microsomes and cytosol, which include most cytochrome P450 (CYP) enzymes and soluble phase II enzymes such as glucuronosyltransferases and sulfotransferases. This study reports on the direct electrochemistry and biocatalytic features of redox-active enzymes in S9 fractions for the first time. We investigated the electrochemical properties of S9 films by immobilizing them onto a high-purity graphite (HPG) electrode and performing cyclic voltammetry under anaerobic (Ar-saturated) and aerobic (O2-saturated) conditions. The heterogeneous electron transfer rate between the S9 film and the HPG electrode was found to be 14 ± 3 s−1, with a formal potential of −0.451 V vs. Ag/AgCl reference electrode, which confirmed the electrochemical activation of the FAD/FMN cofactor containing CYP450-reductase (CPR) as the electron receiver from the electrode. The S9 films have also demonstrated catalytic oxygen reduction under aerobic conditions, identical to HLM films attached to similar electrodes. Additionally, we investigated CYP activity in the S9 biofilm for phase I metabolism using diclofenac hydroxylation as a probe reaction and identified metabolic products using liquid chromatography–mass spectrometry (LC-MS). Investigating the feasibility of utilizing liver S9 fractions in such electrochemical assays offers significant advantages for pharmacological and toxicological evaluations of new drugs in development while providing valuable insights for the development of efficient biosensor and bioreactor platforms.

人类肝脏亚细胞分馏物，包括肝微粒体（HLM）、肝细胞浆分馏物和 S9 分馏物，被广泛用于预测肝脏代谢的体外试验。S9 组份是人肝匀浆的上清液，含有微粒体和细胞质，其中包括大多数细胞色素 P450（CYP）酶和可溶性 II 期酶，如葡萄糖醛酸转移酶和磺基转移酶。本研究首次报道了 S9 馏分中氧化还原活性酶的直接电化学特性和生物催化特性。我们将 S9 薄膜固定在高纯度石墨（HPG）电极上，并在厌氧（氩气饱和）和有氧（氧气饱和）条件下进行循环伏安测定，从而研究了 S9 薄膜的电化学特性。结果发现，S9 薄膜与 HPG 电极之间的异质电子转移率为 14 ± 3 s-1，相对于 Ag/AgCl 参比电极的形式电位为 -0.451 V，这证实了含有 CYP450 还原酶（CPR）的 FAD/FMN 辅助因子作为电极的电子接收器被电化学激活。在有氧条件下，S9 薄膜还表现出催化氧还原作用，这与附着在类似电极上的 HLM 薄膜相同。此外，我们还使用双氯芬酸羟化反应作为探针反应，研究了 S9 生物膜中 CYP 的 I 期代谢活性，并使用液相色谱-质谱法（LC-MS）鉴定了代谢产物。研究在此类电化学测定中利用肝脏 S9 分馏物的可行性为开发中新药的药理学和毒理学评估提供了显著优势，同时也为开发高效生物传感器和生物反应器平台提供了宝贵的见解。

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引用次数: 0

Study on Synthesis and Regulation of PPVI and PPVII in Paris polyphylla with UV 紫外线对巴黎多花植物 PPVI 和 PPVII 合成与调控的研究

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-02 DOI: 10.3390/metabo14080427

Dongjie Geng, Yiqun Sun, Shouzan Liu, Wen Chen, Fei Gao, Yan Bai, Shaobo Zhang

Paris polyphylla Smith var. Chinensis (Franch.) Hara is a medicinal plant that belongs to the Liliaceae family. Its main components are parissaponins, which have excellent medicinal effects such as anti-inflammatory, anti-tumor, etc. Improving the quality of parissaponins through artificial directional regulation has emerged as a practice to meet medical demand and is a new research hotspot. In this paper, P. polyphylla plants were treated with UVA, UVB, and UVC, and the contents of PolyPhyllin VI (PPVI) and PolyPhyllin VII (PPVII), saponin synthase (squalene synthase, SS; cycloartenol synthase, CAS; cytochrome P450, CYP450; and glycosyl transferases, GT) activity, MDA, and the photosynthetic pigment indexes were measured and analyzed. The results showed that PPVII content increased by 32.43% with UVC treatment after 4 h (3.43 mg/g), but the PPVI and PPVII contents in the other groups decreased compared with CK (control group) and they did not return to the original level after 4 h. SS, CAS, CYP450, and GT synthases were activated in varying degrees via UV treatment and increased, respectively, by 22.93%, 10.83%, 20.15%, and 25.98%. Among them, GT, as the last of the synthetases, had a shorter response time to UVB (30 min) and UVC (15 min); the difference was sensible compared with CK. Moreover, UV had a stressing effect and promoted the rapid accumulation of MDA content (increased 17.66%, 34.53%, and 9.65%) and carotenoid (increased 7.58, 5.60, and 7.76 times) within 4 h compared to CK. UVB and UVC radiation visibly improved chlorophyll a content (42.56% and 35.45%), but UVA did not, and the change in chlorophyll b content showed no overt statistical difference. In addition, PPVI and PPVII were negatively correlated with SS, CAS, carotenoids, and MDA (p < 0.05) and positively correlated with CYP450, GT, and chlorophyll a (p < 0.05). This study provides a theoretical basis for using UV light to regulate secondary metabolism in P. polyphylla, which is of great value for production management.

Paris polyphylla Smith var.其主要成分为副皂苷，具有抗炎、抗肿瘤等卓越的药用功效。通过人工定向调节提高副皂苷的质量已成为满足医疗需求的一种做法，也是一个新的研究热点。本文用 UVA、UVB 和 UVC 处理多肉植物，测定并分析了多肉植物的聚皂甙Ⅵ（PPVI）和聚皂甙Ⅶ（PPVII）含量、皂甙合成酶（角鲨烯合成酶，SS；环木菠萝烯醇合成酶，CAS；细胞色素 P450，CYP450；糖基转移酶，GT）活性、MDA 和光合色素指标。结果表明，紫外线处理4 h后（3.43 mg/g），PPVII含量增加了32.43%，但其他组的PPVI和PPVII含量与CK（对照组）相比有所下降，且4 h后仍未恢复到原来的水平；紫外线处理不同程度地激活了SS、CAS、CYP450和GT合成酶，其含量分别增加了22.93%、10.83%、20.15%和25.98%。其中，GT 作为最后一种合成酶，对 UVB（30 分钟）和 UVC（15 分钟）的反应时间较短；与 CK 相比，差异明显。此外，与 CK 相比，紫外线具有应激效应，能促进 MDA 含量（分别增加 17.66%、34.53% 和 9.65%）和类胡萝卜素（分别增加 7.58、5.60 和 7.76 倍）在 4 小时内的快速积累。UVB 和 UVC 辐射明显提高了叶绿素 a 的含量（42.56% 和 35.45%），但 UVA 没有提高，叶绿素 b 含量的变化没有明显的统计学差异。此外，PPVI 和 PPVII 与 SS、CAS、类胡萝卜素和 MDA 呈负相关（p < 0.05），与 CYP450、GT 和叶绿素 a 呈正相关（p < 0.05）。这项研究为利用紫外线调节多肉植物的次生代谢提供了理论依据，对生产管理具有重要价值。

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引用次数: 0

Propionic Acidemia, Methylmalonic Acidemia, and Cobalamin C Deficiency: Comparison of Untargeted Metabolomic Profiles 丙酸血症、甲基丙二酸血症和钴胺素 C 缺乏症：非靶向代谢组图谱的比较

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-02 DOI: 10.3390/metabo14080428

Anna Sidorina, Giulio Catesini, Elisa Sacchetti, Cristiano Rizzo, Carlo Dionisi-Vici

Methylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this study, we used an untargeted metabolomics approach to investigate the biochemical differences and the possible connections among the pathophysiology of each disease. The significantly changed metabolites in the untargeted urine metabolomic profiles of 21 patients (seven MMA, seven PA, seven cblC) were identified through statistical analysis (p < 0.05; log2FC > |1|) and then used for annotation. Annotated features were associated with different metabolic pathways potentially involved in the disease’s development. Comparative statistics showed markedly different metabolomic profiles between MMA, PA, and cblC, highlighting the characteristic species for each disease. The most affected pathways were related to the metabolism of organic acids (all diseases), amino acids (all diseases), and glycine and its conjugates (in PA); the transsulfuration pathway; oxidative processes; and neurosteroid hormones (in cblC). The untargeted metabolomics study highlighted the presence of significant differences between the three diseases, pointing to the most relevant contrast in the cblC profile compared to MMA and PA. Some new biomarkers were proposed for PA, while novel data regarding the alterations of steroid hormone profiles and biomarkers of oxidative stress were obtained for cblC disease. The elevation of neurosteroids in cblC may indicate a potential connection with the development of ocular and neuronal deterioration.

甲基丙二酸血症（MMA）、丙酸血症（PA）和钴胺素 C 缺乏症（cblC）都存在丙酸代谢缺陷。此外，cblC 还参与了同型半胱氨酸的再甲基化过程。这三种疾病会产生不同的表型和复杂的下游代谢影响。在这项研究中，我们采用非靶向代谢组学方法研究了每种疾病的生化差异和病理生理学之间可能存在的联系。通过统计分析（p < 0.05; log2FC > |1|）确定了 21 例患者（7 例 MMA、7 例 PA、7 例 cblC）的非靶向尿液代谢组学图谱中变化明显的代谢物，然后用于注释。注释的特征与可能参与疾病发展的不同代谢途径相关。比较统计显示，MMA、PA 和 cblC 之间的代谢组学特征明显不同，突出了每种疾病的特征物种。受影响最大的途径涉及有机酸（所有疾病）、氨基酸（所有疾病）和甘氨酸及其共轭物（PA）的代谢；转硫途径；氧化过程；以及神经类固醇激素（cblC）。非靶向代谢组学研究强调了三种疾病之间存在的显著差异，指出与 MMA 和 PA 相比，cblC 的特征对比最为相关。针对 PA 提出了一些新的生物标志物，而针对 cblC 疾病则获得了有关类固醇激素谱改变和氧化应激生物标志物的新数据。cblC中神经类固醇的升高可能与眼部和神经元衰退的发展有潜在联系。

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引用次数: 0

A GC-MS Metabolic Study on Lipophilic Compounds in the Leaves of Common Wheat Triticum aestivum L. 普通小麦叶片中亲脂性化合物的气相色谱-质谱代谢研究

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-01 DOI: 10.3390/metabo14080426

Asya R. Vasilieva, Nikolay M. Slynko, Nikolay P. Goncharov, Ljudmila E. Tatarova, Leonid V. Kuibida, Sergey E. Peltek

Common wheat (Triticum aestivum L.) is one of the most valuable cereal crops worldwide. This study examined leaf extracts of 30 accessions of T. aestivum and its subspecies using 48 h maceration with methanol by GC-MS and GCxGC-MS. The plants were grown from seeds of the wheat genetics collection of the Wheat Genetics Sector of the Institute of Cytology and Genetics, SB RAS. The analysis revealed 263 components of epicuticular waxes, including linear and branched alkanes, aliphatic alcohols, aldehydes, ketones, β-diketones, carboxylic acids and their derivatives, mono- and diterpenes, phytosterols, and tocopherols. Hierarchical cluster analysis and principal component analysis were used to identify and visualize the differences between the leaf extracts of different wheat cultivars. Three clusters were identified, with the leading components being (1) octacosan-1-ol, (2) esters of saturated and unsaturated alcohols, and (3) fatty acid alkylamides, which were found for the first time in plant extracts. The results highlight the importance of metabolic studies in understanding the adaptive mechanisms and increasing wheat resistance to stress factors. These are crucial for breeding new-generation cultivars with improved traits.

普通小麦（Triticum aestivum L.）是全球最有价值的谷类作物之一。本研究采用 GC-MS 和 GCxGC-MS 方法，研究了用甲醇浸泡 48 小时的 30 种 T. aestivum 及其亚种的叶提取物。这些植株是从 SB RAS 细胞学和遗传学研究所小麦遗传学部门的小麦遗传学收藏品种子中培育出来的。分析结果显示，表皮蜡质中有 263 种成分，包括直链和支链烷烃、脂肪醇、醛、酮、β-二酮、羧酸及其衍生物、单萜和二萜、植物甾醇和生育酚。采用层次聚类分析和主成分分析来确定和显示不同小麦栽培品种叶提取物之间的差异。结果发现了三个聚类，其主要成分为：(1) 辛可散-1-醇；(2) 饱和及不饱和醇酯；(3) 脂肪酸烷基酰胺，这是首次在植物提取物中发现脂肪酸烷基酰胺。这些结果突显了代谢研究在了解适应机制和提高小麦抗逆性方面的重要性。这些对于培育具有改良性状的新一代栽培品种至关重要。

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引用次数: 0

The Comparative Metabolism of a Novel Hepatocellular Carcinoma Therapeutic Agent, 2,3-Diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide, in Human and Animal Hepatocytes 新型肝细胞癌治疗剂 2,3-二氨基-N-(4-(苯并[d]噻唑-2-基)苯基)丙酰胺在人类和动物肝细胞中的代谢比较

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites

Pub Date : 2024-08-01 DOI: 10.3390/metabo14080425

Young-Heun Jung, Dong-Cheol Lee, Ye-Min Kwon, Eunbee Jang, Garam Choi, Yeoun-Hee Kim, Tae Hwan Kim, Ju-Hyun Kim

[2,3-diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide], named as ETN101, is a novel therapeutic agent for hepatocellular carcinoma. In vitro studies examined ETN101 metabolites in human, mouse, rat, dog, and monkey hepatocytes and identified the drug-metabolizing enzymes involved using cDNA-expressed human recombinant cytochrome P450s (CYPs), carboxylesterases (CESs), N-acetyltransferase (NAT) 1, and human liver cytosol. ETN101 showed similar metabolic stability across hepatocytes from five species, with particularly comparable stability in humans, rats, and monkeys. Its half-life was 75.0 min in humans, 68.9 in rats, 73.1 in monkeys, 120.4 in mice, and 112.7 in dogs. Thirty-four ETN101 metabolites, including the major metabolite M1, were identified using liquid chromatography–high-resolution mass spectrometry. ETN101 was primarily metabolized to M1 and CYP1A2 is exclusively responsible for M1 metabolism. Both NAT1 and NAT2 were responsible for the N-acetylation of M1 to M2. ETN101 remained stable in human CESs. In conclusion, this study provides comprehensive insights into the metabolic characteristics of ETN101, valuable for its toxicological and clinical development.

被命名为 ETN101 的[2,3-二氨基-N-(4-(苯并[d]噻唑-2-基)苯基)丙酰胺]是一种治疗肝细胞癌的新型药物。体外研究检测了 ETN101 在人、小鼠、大鼠、狗和猴子肝细胞中的代谢物，并使用 cDNA 表达的重组人细胞色素 P450s（CYPs）、羧基酯酶（CESs）、N-乙酰转移酶（NAT）1 和人肝细胞溶液鉴定了所涉及的药物代谢酶。ETN101 在五个物种的肝细胞中表现出相似的代谢稳定性，尤其是在人类、大鼠和猴子体内的稳定性相当。它在人体内的半衰期为 75.0 分钟，在大鼠体内为 68.9 分钟，在猴子体内为 73.1 分钟，在小鼠体内为 120.4 分钟，在狗体内为 112.7 分钟。使用液相色谱-高分辨质谱法鉴定了 34 种 ETN101 代谢物，包括主要代谢物 M1。ETN101 主要代谢为 M1，CYP1A2 专门负责 M1 的代谢。NAT1 和 NAT2 负责 M1 到 M2 的 N-乙酰化。ETN101 在人体 CES 中保持稳定。总之，本研究全面揭示了 ETN101 的代谢特征，对其毒理学和临床开发具有重要价值。

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引用次数: 0