Centre for Organismal Studies (COS), Metabolomics Core Technology Platform, Heidelberg University, 69120 Heidelberg, Germany.
Centre for Paediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Int J Mol Sci. 2021 Sep 15;22(18):9979. doi: 10.3390/ijms22189979.
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.
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.
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.
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.
氨基酸在细胞代谢中具有核心作用，细胞内变化导致多种疾病的发病机制，而二肽的作用和特定器官分布在很大程度上尚不清楚。
我们建立了一种灵敏、快速、可靠的 UPLC-MS/MS 方法来定量分析 36 种二肽。分析了 C57BL/6N 野生型小鼠棕色和白色脂肪组织、脑、眼、心脏、肾脏、肝脏、肺、肌肉、坐骨神经、胰腺、脾脏和胸腺、血清和尿液中二肽的图谱，并将其与相应的氨基酸图谱相关联。
在所研究的 36 种二肽中，有 30 种被检测到具有器官特异性分布模式。肉碱和鹅肌肽在所有器官中含量最丰富，在肌肉中含量最高。在肝脏中，Asp-Gln 和 Ala-Gln 浓度较高，在脾脏和胸腺中，Glu-Ser 和 Gly-Asp 浓度较高。在血清中，二肽浓度比器官组织低几个数量级。在所有器官中，C 端脯氨酸（Gly-Pro 和 Leu-Pro）的二肽浓度高于 N 端脯氨酸（Pro-Gly 和 Pro-Leu）的二肽浓度。器官特异性氨基酸图谱与二肽图谱相关，几种氨基酸浓度与二肽的异构形式有关。天冬氨酸、组氨酸、脯氨酸和丝氨酸组织浓度与二肽浓度相关，当氨基酸存在于 C 端而不是 N 端时。
我们的多二肽定量方法证明了器官特异性二肽分布。这种方法使我们能够更多地了解疾病或健康状态下二肽的代谢情况。
