Ketoglutaric Acids

酮戊二酸
  • 文章类型: Journal Article
    Isocitrate dehydrogenase (IDH) is an enzymes involved in a variety of metabolic and epigenetic processes. IDH can be detected in approximately 20% of patients with acute myeloid leukemia (AML), the mutated IDH enzyme acquires new oncogenic enzyme activity and converts α-ketoglutaric acid (α-KG) to the tumor metabolite 2-hydroxyglutaric acid (2-HG), which accumulates at high levels in cells and hinders the function of αKG-dependent enzymes, including epigenetic regulators, resulting in DNA hypermethylation, abnormal gene expression, cell proliferation, and abnormal differentiation, and contributes to leukemia disease progression. IDH mutations have different effects on the prognosis of patients with AML depending on the location of the mutation and other co-occurring genomic abnormalities. This paper will review the latest research progress on the IDH positive AML gene changes, prognosis, and inhibitors.
    UNASSIGNED: 异柠檬酸脱氢酶突变阳性急性髓系白血病的研究进展.
    UNASSIGNED: .异柠檬酸脱氢酶(IDH)是参与多种代谢和表观遗传过程的酶。在大约20%的急性髓系白血病(AML)患者中可检测到IDH突变,突变的IDH酶获得新的致癌酶活性,并将α-酮戊二酸(α-KG)转化为肿瘤代谢物2-羟基戊二酸(2-HG),后者在细胞中以高水平积累并阻碍α-KG依赖性酶的功能,包括表观遗传调节因子,从而导致DNA高甲基化、基因表达的异常、细胞增殖和异常分化,并促进白血病的疾病进展。IDH突变根据突变的位置和其他同时发生的基因组异常,对 AML 患者的预后产生不同的影响。本文将IDH阳性AML的基因改变、预后以及IDH抑制剂的最新研究进展作一概述。.
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  • 文章类型: Journal Article
    作为三羧酸循环的中间体,也称为2-氧戊二酸,α-酮戊二酸(AKG)在维持生理功能和细胞代谢中起重要作用。AKG参与能量代谢,以及碳和氮的代谢;因此,展示各种功能。此外,AKG在身体的各种系统中起重要作用。先前的研究结果表明,AKG可能在多种疾病的进展中起调节作用;因此,它具有作为临床治疗年龄相关疾病的新药的潜力。本文旨在总结AKG的最新研究进展和潜在的临床应用,为今后的研究提供新的方向和空间。
    As an intermediate of the tricarboxylic acid cycle, also known as 2‑oxoglutarate, α‑ketoglutaric acid (AKG) plays an important role in maintaining physiological functions and cell metabolism. AKG is involved in both energy metabolism, and carbon and nitrogen metabolism; thus, exhibiting a variety of functions. Moreover, AKG plays an important role in various systems of the body. Results of previous research indicated that AKG may act as a regulator in the progression of a variety of diseases; thus, it exhibits potential as a novel drug for the clinical treatment of age‑related diseases. The present review aimed to summarize the latest research progress and potential clinical applications of AKG and provided novel directions and scope for future research.
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  • 文章类型: Journal Article
    Currently, a liver biopsy remains the only reliable way to precisely diagnose non-alcoholic fatty liver disease (NAFLD) and establish the severity of liver injury, presence of fibrosis, and architecture remodeling. However, the cost and the intrinsic invasive procedure of a liver biopsy rules it out as a gold standard diagnostic test, and the imaging test are not the best choice due to the price, and currently is being refined. The lack of a biomarker of NAFLD pushes to develop this new line of research. The aim of the present systematic review is to clarify and update all the NAFLD biomarkers described in the literature until recently. We highlight α-ketoglutarate and CK18-F as currently the best potential biomarker of NAFLD. However, due to methodological differences, we propose the implementation of international, multicenter, multiethnic studies with larger population size, and biopsy proven NAFLD diagnosis to analyze and compare α-ketoglutarate and CK18-F as potential biomarkers of the silent evolution of NAFLD.
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  • 文章类型: Journal Article
    Aluminium (Al) toxicity problem in parenteral nutrition solutions (PNS) is decades old and is still unresolved. The aim of this review is to gather updated information about this matter, regarding legislation, manifestations, diagnostics and treatment, patient population at risk and the actions to be taken to limit its accumulation. A structured search using MeSH vocabulary and Title/Abstract searches was conducted in PubMed (http://www.pubmed.gov) up to November 2012. Al is ubiquitous, facilitating its potential for exposure. Nevertheless, humans have several mechanisms to prevent significant absorption and to aid its elimination; therefore, the vast majority of the population is not at risk for Al toxicity. However, when protective gastrointestinal mechanisms are bypassed (for example, parenteral fluids), renal function is impaired (for example, adult patients with renal compromise and neonates) or exposure is high (for example, long-term PNS), Al is prone to accumulate in the body, including manifestations such as impaired neurological development, Alzheimer\'s disease, metabolic bone disease, dyslipemia and even genotoxic activity. A high Al content in PNS is largely the result of three parenteral nutrient additives: calcium gluconate, inorganic phosphates and cysteine hydrochloride. Despite the legislative efforts, some factors make difficult to comply with the rule and, therefore, to limit the Al toxicity. Unfortunately, manufacturers have not universally changed their processes to obtain a lower Al content of parenteral drug products (PDP). In addition, the imprecise information provided by PDP labels and the high lot-to-lot variation make the prediction of Al content rather inaccurate.
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    文章类型: Journal Article
    The fact that men and women are living longer than they have ever done before is something in which we can all rejoice. However, the process of ageing is associated with changes in skeletal, muscular, gastrointestinal, neural hormonal and metabolic processes that seriously affect an individual\'s performance and quality of life. Indeed, such changes can be contributory to a loss of independence in the elderly. This state-of-the art address highlights the main changes found to occur with ageing whilst simultaneously reporting findings of in vivo and in vitro studies designed to elucidate the potential of the Krebs cycle intermediate - alpha-ketoglutaric acid (AKG) in protecting elderly body systems from failing and degradation. The topics of paramount importance include impaired bone structure and strength, amino acid and mineral absorption, muscle performance, as well as highlighting the role of Krebs cycle intermediates in the debilitating changes that occur with end-stage renal failure and the regulation of the lipid metabolism. Finally, focus will be given to the role of 2-oxoglutarate as a potent protective factor in connection with the development of malignant cells in the body.
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    文章类型: Journal Article
    The review sums up the results of studies of (1) physiological growth characteristics of the yeast Yarrowia lipolytica, cultured in the presence of diverse carbon sources (n-alkanes, glucose, and glycerol), and (2) superhigh synthesis of organic acids, which were performed at the Skryabin Institute of Biochemistry and Physiology of Microorganisms of the Russian Academy of Sciences. Microbiological processes of obtaining alpha-ketoglutaric, pyruvic, isocitric, and citric acids are discussed.
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  • 文章类型: Journal Article
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