S-Methyl-L-Ergothioneine to L-Ergothioneine Ratio in Urine Is a Marker of Cystine Lithiasis in a Cystinuria Mouse Model

Abstract

Cystinuria, a rare inherited aminoaciduria condition, is characterized by the hyperexcretion of cystine, ornithine, lysine, and arginine. Its main clinical manifestation is cystine stone formation in the urinary tract, being responsible for 1–2% total and 6–8% pediatric lithiasis. Cystinuria patients suffer from recurrent lithiasic episodes that might end in surgical interventions, progressive renal functional deterioration, and kidney loss. Cystinuria is monitored for the presence of urinary cystine stones by crystalluria, imaging techniques or urinary cystine capacity; all with limited predicting capabilities. We analyzed blood and urine levels of the natural antioxidant L-ergothioneine in a Type B cystinuria mouse model, and urine levels of its metabolic product S-methyl-L-ergothioneine, in both male and female mice at two different ages and with different lithiasic phenotype. Urinary levels of S-methyl-L-ergothioneine showed differences related to age, gender and lithiasic phenotype. Once normalized by L-ergothioneine to account for interindividual differences, the S-methyl-L-ergothioneine to L-ergothioneine urinary ratio discriminated between cystine lithiasic phenotypes. Urine S-methyl-L-ergothioneine to L-ergothioneine ratio could be easily determined in urine and, as being capable of discriminating between cystine lithiasis phenotypes, it could be used as a lithiasis biomarker in cystinuria patient management.

Frailty in Aging and the Search for the Optimal Biomarker: A Review

“…Relative to acetyl-carnosine, N-acetyl derivatives of histidine, such as carnosine, exist in mammalian cardiac and skeletal muscle, and the total concentration of these imidazoles can be within the measured range of L-carnosine in skeletal muscle (~10 mM) [ 131 , 132 ]. On the other hand, ergothioneine (ERG) is an unusual betaine thiohistidine amino acid that has potent antioxidant activities and also promotes neuronal stem cell differentiation [ 133 , 134 , 135 , 136 ]. As for trimethyl-histidine, it is formed by post-translational methylation of histidine residues in actin and myosin, and its plasma concentration and urinary excretion are sensitive markers of myofibrillar protein degradation [ 137 , 138 ].…”

Structure and Substrate Specificity of S-Methyl Thiourocanate Hydratase

“…S -methyl ergothioneine has been identified as an excreted metabolite in animals. − The same compound was also isolated from the deepwater sponge Macandrewia azorica . Enzymes that catalyze ergothioneine methylation have not yet been described, and it is unclear whether the methylation of ergothioneine serves any specific physiological function.…”