Isolation and Identification of N,N- and N,N' -Dimethylarginine, Nε-Mono-, Di-, and Trimethyllysine, and Glucosylgalactosyl- and Galactosyl-δ-hydroxylysine from Human Urine

Kawaguchi, Yasuo; Akazawa, Shigenori

doi:10.1016/s0021-9258(18)62716-4

Cited by 390 publications

(41 citation statements)

References 27 publications

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“…This is because almost all SDMA is cleared by renal filtration (Kakimoto & Akazawa, 1970). We found that both creatinine and SDMA had strong associations with NF-L, supporting the possibility of renal dysfunction being associated with neurodegenerative changes.…”

Section: Discussionsupporting

confidence: 62%

Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults

Chatterjee

Cheong

Bhatnagar

et al. 2020

Journal of Neurochemistry

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF-L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF-L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass-spectrometry (AbsoluteIDQ® p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans-4-hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF-L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid-β load (Aβ ±) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF-L in both Aβ-and Aβ+ groups, ADMA, proline, arginine, asparagine, phenylalanine

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Section: Discussionsupporting

confidence: 62%

Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults

Chatterjee

Cheong

Bhatnagar

et al. 2020

Journal of Neurochemistry

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“…Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) amino acids are formed by protein arginine Nmethyltransferases from methylated proteins on arginine residues and they are considered inhibitors of nitric oxide [38]. ADMA was first studied, while SDMA was considered an inert molecule, being first isolated from human urine [39]. These methylarginines are metabolized by two enzymes-dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and -2 (DDAH-2)-as well as alanine-glyoxylate aminotransferase 2 (AGXT2).…”

Section: Introductionmentioning

confidence: 99%

Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma

et al. 2020

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Posttranslational modifications are dynamic enzymatic-mediated processes, regulated in time and space, associated with cancer development. We aimed to evaluate the significance of posttranslational modifications in the pathogenesis of clear cell renal cell carcinoma. The authors developed a prospective, observational study during a period of three years and included 55 patients with localized renal cell carcinoma and 30 heathy subjects. Glycosylation, nitration and carbonylation, thiol-disulfide homeostasis, methylation, phosphorylation and proteolytic cleavage were evaluated in the serum of the evaluated subjects in the present study. Our results showed some characteristics for early ccRCC: high production of cytokines, substrate hypersialylation, induced nitrosative and carbonylic stress, arginine hypermethylation, thiol/disulfide homeostasis (TDH) alteration, the regulatory role of soluble receptors (sRAGE—soluble receptor for advanced glycation end products, sIL-6R—soluble receptor for Interleukin 6) in RAGE and IL-6 signaling, the modulatory effect of TK1—thymidine kinase 1 and TuM2-PK—tumoral pyruvate-kinase 2 in controlling the level of phosphometabolites in neoplastic cells. These data could be the initial point for development of a panel of biomarkers such as total sialic acid, orosomucoids, nitrotyrosine, carbonylic metabolites, Asymmetric Dimethylarginines (ADMA), Symmetric Dimethylarginines (SDMA), and thiol-disulfide equilibrium for early diagnosis of ccRCC. Moreover, they could be considered a specific disease posttranslational modification signature which underlines the transition from early to advanced stages in this neoplasia, and of a therapeutic target in kidney oncogenesis.

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“…Asymmetric dimethylarginine is formed by methylation of protein containing arginine residues after translation by protein arginine methyl transferase (PMRT) 26 . In the 1970s, Kakimoto et al 27 first isolated and identified ADMA from human urine. ADMA can be excreted directly by the kidney and can also be catabolized and eliminated by dimethyl arginine dimethylamine hydrolase (DDAH).…”

Section: Discussionmentioning

confidence: 99%

A systematic review of the correlation between serum asymmetric dimethylarginine, carotid atherosclerosis and ischaemic stroke

Qin

Tang

Huang

et al. 2021

Eur J Clin Investigation

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Objective: To investigate the correlation between serum asymmetric dimethylarginine (ADMA) and the risk of ischaemic stroke and carotid atherosclerosis in adults. Methods: We systematically searched PubMed, EMBASE, Web of Science and other databases for relevant studies on serum ADMA and ischaemic stroke or carotid atherosclerosis, which were published from December 1980 to December 2019. The quality of the included studies was evaluated according to the Cochrane system evaluation standard. The difference in serum ADMA level between ischaemic stroke and control group was selected as the effect size (standardized mean difference, SMD).The pooled analysis was performed using Review Manager (V.5.3). Results: According to the selection criteria, thirteen studies were included in the meta-analysis after screening. Nine studies compared ADMA levels between the ischaemic stroke group and healthy control group, involving a total of 1315 and 880 subjects in the two groups, respectively. Pooled effect sizes were calculated using the random-effects model due to the high heterogeneity (I 2 = 93%, P < .00001). The level of serum ADMA in patients with ischaemic stroke was significantly higher than that in healthy people (SDM = 0.69, 95% CI [0.32, 1.06], P = .0002). Seven of the thirteen articles compared ADMA levels between the carotid arteriosclerosis group and the healthy control group, with 559 and 330 subjects in the two groups, respectively. The random-effects model was applied due to the high heterogeneity (I 2 = 91%, P < .00001). The level of serum ADMA in patients with carotid arteriosclerosis was significantly higher than that in healthy people (SDM = 1.03, 95% CI [0.49, 1.57], P = .0002). Conclusion:The serum ADMA may be related to ischaemic stroke, and it is a risk factor for carotid atherosclerosis.

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Isolation and Identification of N,N- and N,N' -Dimethylarginine, Nε-Mono-, Di-, and Trimethyllysine, and Glucosylgalactosyl- and Galactosyl-δ-hydroxylysine from Human Urine

Cited by 390 publications

References 27 publications

Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults

Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults

Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma

A systematic review of the correlation between serum asymmetric dimethylarginine, carotid atherosclerosis and ischaemic stroke

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