Creatine Is a Scavenger for Methylglyoxal under Physiological Conditions via Formation of N-(4-Methyl-5-oxo-1-imidazolin-2-yl)sarcosine (MG-HCr)

Abstract

Following incubation of methylglyoxal and creatine under physiological conditions, N-(4-methyl-5-oxo-1-imidazolin-2-yl)sarcosine (MG-HCr) was isolated and identified by NMR and mass spectrometry. Due to its rapid formation, MG-HCr represents a specific product following "scavenging" of methylglyoxal by creatine. Using hydrophilic interaction chromatography coupled to mass spectrometry, MG-HCr was analyzed in urine samples of healthy volunteers. Daily MG-HCr excretion of nonvegetarians ranged from 0.35 to 3.84 μmol/24 h urine (median: 0.90 μmol/24 h urine) and of vegetarians from 0.11 to 0.31 μmol/24 h urine (median: 0.19 μmol/24 h urine), indicating that formation of MG-HCr in vivo is influenced by the dietary intake of creatine. The trapping of methylglyoxal by creatine may delay the formation of advanced glycation compounds in vivo and, therefore, could be of special importance in situations in which the body has to deal with pathophysiologically increased amounts of dicarbonyl compounds ("carbonyl stress"), for instance in diabetic patients.

Settings The Role of Methylglyoxal Accumulation on Cognitive Function Impairment of Chronic Hemodialysis Patients: an Observational Study

“…19 Previous studies have shown an increased level of MG between 0.25 -0.75 µmol/L can significantly cause neuronal damage. 16,20,21 In this study, the mean level of MG were almost 10 times higher than the cutoff point of normal MG level, consistent with current evidence available.…”

“…22 Cognitive impairment consists of dysfunction in at least two components of cognitive function. 22 Based on MMSE score, the severity of cognitive impairment is divided into three groups: mild (20)(21)(22)(23)(24), moderate (13)(14)(15)(16)(17)(18)(19)(20), and severe (<12). 23 Tests on the MMSE questionnaire include orientation tests, to assess awareness and memory, and registration test to assess working memory.…”

Identification and characterization of reaction products of 5‐hydroxytryptamine with methylglyoxal and glyoxal by liquid chromatography/tandem mass spectrometry

“…The product was in fact detected in human urine samples using nuclear magnetic resonance and liquid chromatography/mass spectrometry (LC/MS) techniques. Deng and coworkers investigated the reaction of dopamine, a neurotransmitter with MGO, and reported formation of a novel product (1‐acetyl‐6, 7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline). They found increased levels of the reaction product in brain samples of patients with Parkinson's disease.…”

Investigations on the Reaction of C3 and C6 α-Dicarbonyl Compounds with Hydroxytyrosol and Related Compounds under Competitive Conditions

“…9 The formation and accumulation of AGEs in vivo have drawn major attention because of their possible association with the aging process as well as the development of chronic diseases, such as Alzheimer's disease, atherosclerosis, chronic inflammatory diseases, cardiovascular diseases, or diabetes mellitus and its numerous long-term complications.10−13 Human plasma levels for 3-deoxyglucosone (3-DG), methylglyoxal (MGO), and glyoxal (GO) have been estimated to reach 0.16−1.24 μmol/L, increasing to values of 4.09 μmol/L in diabetes and uremic patients and thus contributing to systemic carbonyl stress.14 Pharmaceutical interventions against glycation were initially carried out with substances such as aminoguanidine; however, their relevant side effects in clinical trials have led to the search for natural products with the same ability.12,15 Natural plant extracts are the priority source for searching compounds that mitigate the formation of AGEs,15 although recently the antiglycative activity of other naturally occurring substances such as creatine has been highlighted. 16 Because certain stages of the glycation process are driven by redox reactions, polyphenols have been largely investigated by applying their antioxidant capacity to mitigate the radical-mediated reactions. Moreover, the ability of certain polyphenols to trap reactive carbonyl species has recently been pointed out.13,15,17 However, investigations on the carbonyl trapping activity have only been carried out with MGO and GO, whereas their activity against C6 α-dicarbonyl compounds has not been determined, although these compounds are mostly present in higher concentrations than C2 and C3 α-dicarbonyl structures.4 Additionally, 3-DG is the most abundant C6 α-dicarbonyl in vivo, ranging from 35 to 56 pmol/mL in plasma of healthy subjects.1,11…”