以三种非极性氨基酸为例探讨氨基酸合成代谢的化学原理

由于氨基酸代谢的多样性和相对独立性,在基础教学中对相关内容的讨论和推广对培养21世纪新型跨学科人才是极其重要的。本文将以三种基本的非极性天然氨基酸——缬氨酸、异亮氨酸和亮氨酸为例,从氨基酸合成代谢的内容和方式等方面做教学模式的探索,并尝试归纳与总结自然界采取这样代谢路径的原因和逻辑。同时,其中相关的生物化学过程也体现出生命体系所采取的不同寻常的合成路径和反应机制。这对于本科生而言不仅是具有趣味性与启发性的良好的素材,也是了解目前研究热点和积累知识的有效渠道,期望对其后续深入的学习和研究有帮助。     

再生障碍性贫血患者中药治疗前后微量元素变化初步观察

对20例再生障碍性贫血患者（以下简称再障）头发中12种微量元素的含量进行测定，与正常人做对照，结果发现，阴虚型患者锂、钙、锶、铬显著减少，阴虚型患者锌、镁、钡、钙、锂明显下降，阴阳俱虚型患者则12种元素均减少，并对本院治疗再障贫血的24味中药的微量元素的含量也进行测定。结合微量元素变化对指导再障的辩证组方和辩证施治提供新的思路，同时系统观察再障贫血10例治疗前后微量元素的变化情况，从微量元素角度探求再障的发症因素，认为与部分微量元素缺乏有关，补充相关的微量元素，再障患者可恢复健康。     

Problems of iron metabolism with special reference to biochemical, physiological, and clinical aspects

A brief account of the functions and chemical structures of the principal iron compounds found in the human body is followed by a discussion of the physiology of iron metabolism, starting with its resorption, continuing with its transport and assimilation by the body cells, and concluding with its elimination. Special attention is paid to the problems of intracellular and extracellular transport of iron. A number of diseases with characteristic disturbances of the iron metabolism are also briefly described.     

Calorimetry of dual limitations in yeast cultures

Chemostat cultures of one aerobic fermenting yeast (Saccharomyces cerevisiae) and one aerobic respiring yeast (Kluyveromyces fragilis) have been grown under dual C + N limitation in an isothermal reaction calorimeter. The dual limitations resulted in uncoupled oxidation of part of the glucose, which enabled the culture to adapt the ratio of nitrogen to carbon consumption rates precisely to the N/C ratio that was fed into the calorimeter. This conclusion has been reached based on the calorimetric measurements, which reflect uncoupled respiration conspicuously as abnormal heat yields or ratios of heat release per biomass grown.     

Quality properties of pre- and post-rigor beef muscle after interventions with high frequency ultrasound

The delivery of a consistent quality product to the consumer is vitally important for the food industry. The aim of this study was to investigate the potential for using high frequency ultrasound applied to pre- and post-rigor beef muscle on the metabolism and subsequent quality. High frequency ultrasound (600 kHz at 48 kPa and 65 kPa acoustic pressure) applied to post-rigor beef striploin steaks resulted in no significant effect on the texture (peak force value) of cooked steaks as measured by a Tenderometer. There was no added benefit of ultrasound treatment above that of the normal ageing process after ageing of the steaks for 7 days at 4 °C. Ultrasound treatment of post-rigor beef steaks resulted in a darkening of fresh steaks but after ageing for 7 days at 4 °C, the ultrasound-treated steaks were similar in colour to that of the aged, untreated steaks. High frequency ultrasound (2 MHz at 48 kPa acoustic pressure) applied to pre-rigor beef neck muscle had no effect on the pH, but the calculated exhaustion factor suggested that there was some effect on metabolism and actin-myosin interaction. However, the resultant texture of cooked, ultrasound-treated muscle was lower in tenderness compared to the control sample. After ageing for 3 weeks at 0 °C, the ultrasound-treated samples had the same peak force value as the control. High frequency ultrasound had no significant effect on the colour parameters of pre-rigor beef neck muscle. This proof-of-concept study showed no effect of ultrasound on quality but did indicate that the application of high frequency ultrasound to pre-rigor beef muscle shows potential for modifying ATP turnover and further investigation is warranted.     

Targeted metabolomics in cultured cells and tissues by mass spectrometry: Method development and validation

Metabolomics is the identification and quantitation of small bio-molecules (metabolites) in biological samples under various environmental and genetic conditions. Mass spectrometry provides the unique opportunity for targeted identification and quantification of known metabolites by selective reaction monitoring (SRM). However, reproducibility of this approach depends on careful consideration of sample preparation, chemical classes, and stability of metabolites to be evaluated. Herein, we introduce and validate a targeted metabolite profiling workflow for cultured cells and tissues by liquid chromatography–triple quadrupole tandem mass spectrometry. The method requires a one-step extraction of water-soluble metabolites and targeted analysis of central metabolites that include glycolysis, amino acids, nucleotides, citric acid cycle, and the hexosamine biosynthetic pathway. The sensitivity, reproducibility and molecular stability of each targeted metabolite were assessed under experimental conditions. Quantitation of metabolites by peak area ratio was linear with a dilution over a 4 fold dynamic range with minimal deviation R² = 0.98. Inter- and intra-day precision with cells and tissues had an average coefficient of variation <15% for cultured cell lines, and somewhat higher for mouse liver tissues. The method applied in triplicate measurements readily distinguished immortalized cells from malignant cells, as well as mouse littermates based on their hepatic metabolic profiles.     

Sodium Bicarbonate Nanoparticles for Amplified Cancer Immunotherapy by Inducing Pyroptosis and Regulating Lactic Acid Metabolism

Although immunotherapy has a broad clinical application prospect, it is still hindered by low immune responses and immunosuppressive tumor microenvironment. Herein, a simple and drug-free inorganic nanomaterial, alkalescent sodium bicarbonate nanoparticles (NaHCO₃ NPs), is prepared via a fast microemulsion method for amplified cancer immunotherapy. The obtained alkalescent NaHCO₃ regulates lactic acid metabolism through acid-base neutralization so as to reverse the mildly acidic immunosuppressive tumor environment. Additionally, it can further release high amounts of Na⁺ ions inside tumor cells and induce a surge in intracellular osmolarity, and thus activate the pyroptosis pathway and immunogenic cell death (ICD), release damage-associated molecular patterns (DAMPs) and inflammatory factors, and improve immune responses. Collectively, NaHCO₃ NPs observably inhibit primary/distal tumor growth and tumor metastasis through acid neutralization remitted immunosuppression and pyroptosis induced immune activation, showing an enhanced antitumor immunity efficiency. This work provides a new paradigm for lactic acid metabolism and pyroptosis mediated tumor treatment, which has a potential for application in clinical tumor immunotherapy.     

MS analysis reveals O-methylation of L-lactate dehydrogenase from pancreatic ductal adenocarcinoma cells

L-lactate dehydrogenase (LDH) converts pyruvate to lactate when oxygen is absent or in short supply, and the enzyme plays a crucial role in cancer metabolism. The functions of many mammalian proteins are modulated by posttranslational modifications (PTMs), and it has been reported that LDH was subjected to several PTMs, including phosphorylation, acetylation, and methylation. In this present work, we characterized the PTMs of LDH from pancreatic ductal adenocarcinoma (PDAC) cells by electrophoresis and mass spectrometry, and identified 13 O-methylated residues from the enzyme. In addition, our qualitative analysis revealed differential methylation of LDH from normal duct cells. The preliminary findings from this study provide important biochemical information toward further understanding of the LDH modifications and their functional significance in pathophysiological processes of pancreatic cancer.