Regulation of Calcium Absorption in Caco-2 Cells by Aspartic Acid, Glutamic Acid and Their Glycine Dipeptides

In order to investigate the mechanism of aspartic acid, glutamic acid and their glycine dipeptides on calcium ion uptake, the isothermal titration calorimetry technique, electrochemistry, and Caco-2 cell model combined with quantum mechanical calculation (density functional theory) were used to investigate the interactions between aspartic acid and glutamic acid, as well as their glycine dipeptides. The results showed that aspartic acid and glutamic acid form complexes with calcium ions through exothermic reactions driven by enthalpy and entropy, while their dipeptides interacted with calcium ions by entropy-driven endothermic reactions. In addition, dipeptides exhibited stronger calcium binding capacity than the single amino acids. Quantum chemical calculations showed that the carboxyl groups in the amino acid/dipeptide were the main binding site of calcium ions, while under alkaline conditions, the amino group could also participate in calcium binding, leading to a calcium binding site shift. Caco-2 cell uptake experiments showed that aspartic acid, glutamic acid and their dipeptides could promote calcium absorption. Among them, Gly-Glu dipeptide had the best promotion effect, and the calcium absorption rate was 1.33±0.115. Furthermore, there was no clear correlation between the ability to promote calcium absorption and the ability to bind calcium ions. However, it was more closely related to its electron affinity. The results elucidated the interactions between aspartic acid, glutamic acid and their glycine dipeptides and calcium ions, providing scientific basis for further development of calcium supplements