Creatine
Linda M. Castell, Samantha J. Stear (Nottingham), Louise M. Burke in Nutritional Supplements in Sport, Exercise and Health, 2015
For instance, despite allegations of detrimental effects of oral creatine supplementation on liver metabolism, studies on humans have not shown any significant increase in plasma urea, nor liver enzyme activity, during five years of creatine supplementation (Poortmans and Francaux, 2008). No reports have observed a modification of the glomerular filtration rate, nor the presence of microalbuminuria (Portmans and Francaux, 2000, 2008). All values remained within the normal range adapted for the age range. Experimentally, an excess conversion of creatine to sarcosine may result in cytotoxic agents such as methylamine. However, in humans taking up to 20g creatine per day for two weeks (Poortmans et al., 2005; Sale et al., 2009), urine methylamine excretion remains largely under the upper limit for healthy individuals.
Multiple acyl CoA dehydrogenase deficiency/glutaric aciduria type II ethylmalonic-adipic aciduria
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The mitochondrial oxidations of glutaryl-CoA and other intermediates in branched-chain amino acid metabolism, and the β-oxidation of fatty acids (see Figure 45.1) are catalyzed by mitochondrial flavinadenine dinucleotide (FAD)-dependent enzymes [8–11]. Each of the dehydrogenase enzymes of fatty acid oxidation, and the amino acid catabolic enzymes catalyze the dehydrogenation of saturated acylCoA compounds to form the 2,3-unsaturated or enoylCoA thioesters (Figure 45.2). Both sarcosine and dimethylglycine are catabolized by specific N-methyldehydrogenases containing covalently bound FAD and dissociable folic acid cofactors [12–14], and thus these two compounds may also accumulate in this disease. Each dehydrogenase enzyme contains a molecule of FAD.
The Renin-Angiotensin System
Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan in 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
Nutrition and schizophrenia: associations worthy of continued revaluation
Published in Nutritional Neuroscience, 2023
Mimi Tang, Tingyu Zhao, Ting Liu, Ruili Dang, Hualin Cai, Ying Wang
There have also been trials comparing the efficacy of these two amino acids with placebo. Lane et al. studied the efficacy of sarcosine and D-serine at the same dose compared to placebo in patients with acute exacerbations of schizophrenia and patients with chronic stable schizophrenia. The result showed sarcosine is superior to D-serine and is not only beneficial for patients with long-term stable disease, but also for acute schizophrenia patients [119, 131]. Whereas Buchanan et al. showed that neither glycine nor D-cycloserine is a universally effective treatment option for the treatment of negative symptoms or cognitive impairment, especially in patients with moderate to severe persistent negative symptoms and cognitive impairment in schizophrenia. This result may be due to differences in adherence among different populations, doses of antipsychotics, and inconsistencies in baseline negative symptoms [132].
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].
Related Knowledge Centers
- Chloroacetic Acid
- Choline
- Dimethylglycine
- Glycine
- Methylamine
- Surfactant
- Amino Acid
- Zwitterion
- Sarcosine Dehydrogenase
- Glycine N-Methyltransferase