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Liquid Biopsies for Pancreatic Cancer: A Step Towards Early Detection
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Joseph Carmicheal, Rahat Jahan, Koelina Ganguly, Ashu Shah, Sukhwinder Kaur
Rapidly proliferating tumor cells undergo ROS mediated spontaneous DNA damage and aberrant chemical modifications like DNA methylation and histone acetylation/ deacetylation leading to the formation of a pool of modified bases. Owing to DNA repair mechanisms and enhanced cellular turnover, those altered bases are generally excised and expelled from the system. Elevated levels of such modified nucleosides in the urine are evolving as important biomarkers in different cancers including liver, breast, colorectal cancer, hepatocellular carcinoma and leukemia [37-39]. Sarcosine is produced by transfer of an N-methyl group on glycine during DNA methylation and its level in the urine is shown to increase during prostate cancer progression and metastasis [40]. This finding indicates that one of the potential metabolites that can be used as a cancer biomarker are modified nucleosides.
Multiple acyl CoA dehydrogenase deficiency/glutaric aciduria type II ethylmalonic-adipic aciduria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
In the neonatal onset disease, the concentrations of the amino acids, citrulline, lysine, ornithine, and proline are elevated in plasma and urine. Hydroxyproline excretion may be high, consistent with a generalized amino aciduria. The excretion of arginine may also be very high. In the later onset disease, there may be elevated concentrations of sarcosine in blood and urine [37, 40, 45]. Concentrations of carnitine in the blood may be low [57].
The Renin-Angiotensin System
Published in Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan, Pharmacological and Therapeutic Aspects of Hypertension, 2020
Other substitutions at position 1, designed to reduce degradation of the analogues by aminopeptidases such as [β-Asp1], do not produce such potent antagonists as the [Sar1]-derivatives. This suggests that sarcosine at this site, in addition to protecting the molecule from aminopeptidase, may also enhance binding of the molecules to the receptor.286,645
Emerging therapeutic targets for schizophrenia: a framework for novel treatment strategies for psychosis
Published in Expert Opinion on Therapeutic Targets, 2021
Susan F. Sonnenschein, A Grace
Numerous glutamate-targeting compounds have been evaluated in clinical trials. NMDA receptor co-agonists, including D-cycloserine, D-serine, and glycine, were among the earliest studied in an effort to enhance NMDA-mediated interneuron function [90], thereby increasing inhibition of pyramidal neurons. Despite initial promise in clinical trials, none of these compounds passed phase 2 or phase 3 clinical trials as either a monotherapy or adjunct to current treatments [91,92]. Selective glycine transporter 1 (GlyT1) inhibitors, such as sarcosine and biopertin have also been tested as an alternative method to increase the availability of glycine at NMDA receptors [93]. Sarcosine has demonstrated success in clinical trials as an adjunct treatment in early clinical trials in improving positive, negative, and cognitive symptoms [94,95] with some evidence for greater efficacy than NMDA receptor agonists [96]. However, not all trials have shown significant results with GlyT1 inhibitors, such as when added to clozapine or tested as a monotherapy [97–99]. D-amino acid oxidase (DAAO) inhibition with compounds such as sodium benzoate has also recently been explored as a method of enhancing NMDA receptor activation by blocking D-amino acid metabolism. Sodium benzoate has produced promising results as an adjunctive therapy in early clinical trials [100–102]. Larger clinical trials are needed to better assess the potential benefits of NMDA receptor-targeting drugs.
The applications of metabolomics in the molecular diagnostics of cancer
Published in Expert Review of Molecular Diagnostics, 2019
Pro Kit Cheung, Man Hin Ma, Hing Fung Tse, Ka Fai Yeung, Hin Fung Tsang, Man Kee Maggie Chu, Chau Ming Kan, William Chi Shing Cho, Lawrence Bo Wah Ng, Lawrence Wing Chi Chan, Sze Chuen Cesar Wong
Sarcosine is a potential biomarker which has the greatest concern [34]. It was first discovered by Sreekumar using LC/GC MS in 2009. From the unbiased metabolomic profiling of urine, it was found that the level of sarcosine increases greatly when prostate cancer proceeds to metastasis. Increase of sarcosine level was also found in invasive prostate cancer cell line. Therefore, sarcosine was believed to be a biomarker to monitor the invasion and aggressivity of prostate cancer. However, null and non-specific findings are found in studies which try to reproduce the results. The reasons for that could be individual differences in sarcosine level and measurement errors due to different analyzing tools. Also, there is a problem in measuring the correct ratio of sarcosine to creatine in studies of urine which could also account for the inconsistency of different researches [34].
Quantitative analysis of sarcosine with special emphasis on biosensors: a review
Published in Biomarkers, 2019
C.S. Pundir, Ritu Deswal, Parveen Kumar
Sarcosine is synthesized by the glycine N-methyltransferase (GMT) and metabolized by sarcosine dehydrogenase (SARDH) enzyme (Heger et al.2016). An overview of sarcosine metabolism as well as various biological functions of sarcosine is represented in Figure 1. Sarcosine is present in a variety of food sources viz egg yolks, legumes, nuts, vegetables, turkey, ham, and other meats (Allen et al.1993). In the human body, it is present in skeletal muscles and prostate. Sarcosine represents an essential role in methyl donation, homeostasis and the one-carbon cycle. It is a major factor in nucleic acid synthesis. It accelerates the cell division and, therefore, helps in the growth and development of the foetus (Fasman and Blout 1963). Sarcosine has a distinct mild sweet flavour. An ingredient of toothpaste for decades, it prevents cavities and causes foaming. The increased levels of sarcosine have been implicated in pathophysiology of multiple diseases like Alzheimer, dementia, prostate cancer, colorectal cancer, stomach cancer, sarcosinemia, dimethylglycine dehydrogenase deficiency, eosinophilic esophagitis and Lewy body disease (Bar-Joseph et al.2012, Soliman et al.2012, Tsuruoka et al.2013). It is also a promising biomarker for prostate cancer. Research during past decades uncovered the clinical benefits of sarcosine in treating mental health disorders, including schizophrenia, depression, obsessive-compulsive disorder, seizures and stroke (Wu et al.2011). Serum sarcosine level is normally 80.8 ng/mL and 102.3 ng/mL in females and males respectively (Strzelecki et al.2015). Various physicochemical properties of sarcosine are summarized in Table 1.