Creatine (CR) a therapeutic food supplement has been used for treating muscle disorders (Kley 2013), amyotrophic lateral sclerosis/motor neuron disease (Pastula 2010). A Pharmacokinetic model of this endogenous metabolite as a food supplement has been recently proposed by (Persky 2003). Large doses of CR as a dietary supplement is being used by athletes and patients suffering from muscle, neurodegenerative and brain disorders (Kley 2013). Recently we reported anti-glycosylation activity of Okra Seed Extracts (OSE) and found the inhibitory activity of advanced glycation end products (AGEs) of (OSE) almost comparable to 2-aminoguanidine and metformin, well-established inhibitors for (AGEs). Combination of OSE with 2-aminoguanidine or metformin further enhanced the inhibitory activity in a dose dependent manner (ACS Book Symposium 2012, ACS 247, 248, 249). The inhibitory effects were assessed using SDS-PAGE , specific fluorescence spectroscopy and structural changes in protein concentrations observed via Nano drop spectrophotometry (J. Environ Sci. and Engineering (6A, 2016, 4A 2016). Creatine shows structural similarities to 2- amino guanidine specifically guanidine moiety which is present in both molecules. Our present studies describe the trapping efficiency of CR specifically a reaction with 1,2 dicarbonyl compound methylglyoxal (MGO) a potent neurotoxin. Incubations with solutions of MGO (10 mM, 40% solution in H2O) and CR (50 mM, in excess) in phosphate buffer (50mM, pH 7.4) and microwaved for 50 seconds at 4 seconds intervals.The reaction mixture resolved by analytical and preparatory TLC. The UV-Vis Nanodrop and exhibited lamda 276 nm showing quanitative conversion. LC-MS/MS exhibited M/Z=184 [15%], M/Z=256/257 [90%], M/Z=513/514 [2M+H]+ [100%], [2M+H+Na]+ = [535, 12%]. Since oxidative stress plays an important role in neurodegenerative diseases, we propose the hypothesis that the administration of creatine down-regulates RAGE, the receptor for advanced glycation end products (AGEs), decreasing the generation of Reactive Oxygen Species (ROS), and deactivating Ras-Map kinase pathway and nuclear translocation of NF-kB which are linked to diabetes type-2, cancer, inflammation and autoimmune diseases. The adduct of creatine with methylglyoxal forms N-(4-Methyl-5oxo-1-imidazolin-2-yl)sarcosine (MG-HCr) which gets excreated in the urine relieving the condition of dialysis-related amlydolsis. The mechanism of MG-HCr with another mole of MGO will be discussed

Creatine a scavenger of methylglyoxal (MGO), a potent neurotoxin: Physiological role of creatine in energy metabolism

255th National Meeting (2018)

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