A Novel UPLC-MS/MS Method Identifies Organ-Specific Dipeptide Profiles

Abstract

Background: Amino acids have a central role in cell metabolism, and intracellular changes contribute to the pathogenesis of various diseases, while the role and specific organ distribution of dipeptides is largely unknown. Method: We established a sensitive, rapid and reliable UPLC-MS/MS method for quantification of 36 dipeptides. Dipeptide patterns were analyzed in brown and white adipose tissues, brain, eye, heart, kidney, liver, lung, muscle, sciatic nerve, pancreas, spleen and thymus, serum and urine of C57BL/6N wildtype mice and related to the corresponding amino acid profiles. Results: A total of 30 out of the 36 investigated dipeptides were detected with organ-specific distribution patterns. Carnosine and anserine were most abundant in all organs, with the highest concentrations in muscles. In liver, Asp-Gln and Ala-Gln concentrations were high, in the spleen and thymus, Glu-Ser and Gly-Asp. In serum, dipeptide concentrations were several magnitudes lower than in organ tissues. In all organs, dipeptides with C-terminal proline (Gly-Pro and Leu-Pro) were present at higher concentrations than dipeptides with N-terminal proline (Pro-Gly and Pro-Leu). Organ-specific amino acid profiles were related to the dipeptide profile with several amino acid concentrations being related to the isomeric form of the dipeptides. Aspartate, histidine, proline and serine tissue concentrations correlated with dipeptide concentrations, when the amino acids were present at the C- but not at the N-terminus. Conclusion: Our multi-dipeptide quantification approach demonstrates organ-specific dipeptide distribution. This method allows us to understand more about the dipeptide metabolism in disease or in healthy state.

Serum metabolomics reveal pathways associated with protective effect of ginsenoside Rg3 on immune stress

“…Previous studies demonstrated LPS challenge caused alterations in lipid and protein metabolism in different animals ( Wan et al, 2017 ; Wang et al, 2017 ; Chirivi et al, 2022 ). In present study, taurolithocholic acid, myristoleic acid, stearoylcarnitine, PC (16:0/16:0), 1-Hexadecyl-sn-glycero-3-phosphocholine and Ser-Arg were significantly altered, suggesting that the abnormal degradation of lipid and protein were involved in the pathogenesis of stress in chicks ( Ozawa et al, 2020 ; Heidenreich et al, 2021 ). Therefore, the changed metabolites may explain the decreased growth performance of broilers with stress induced by LPS challenge.…”

Extensive profiling of histidine-containing dipeptides reveals species- and tissue-specific distribution and metabolism in mice, rats and humans

“…We also uncover that N-acetylcarnosine is the primary circulating HCD in human plasma and is continuously secreted from skeletal muscle into the circulation, which is further increased by physical exercise. An overview of the main findings is visualized in Previous endeavors to profile HCDs mostly focused on rodent tissues, and resulted in fragmented and sometimes contradictory literature (13,(22)(23)(24)(25). Our systematic approach and very sensitive state-ofthe-art UHPLC-MS/MS methodology facilitate direct comparison between tissues and species.…”

“…Previous endeavors to profile HCDs mostly focused on rodent tissues, and resulted in fragmented and sometimes contradictory literature ( 13, 22–25 ). Our systematic approach and very sensitive state-of-the-art UHPLC-MS/MS methodology facilitate direct comparison between tissues and species.…”

Regional Brain Analysis of Modified Amino Acids and Dipeptides during the Sleep/Wake Cycle

“…This finding also emphasizes the importance of the brain's regional metabolomic analysis, as recent mapping of the regional distribution of dipeptides revealed particular localization patterns [47,48]. In addition, differential tissue distribution has been observed for isomeric dipeptides depending on the C-terminal amino acid [49].…”