Establishment Of Adenylate Succinic Acid (salt) Biosynthesis Method And Its Pharmacological Research

Adenylosuccinic acid(S-AMP)is a natural adenosine compound in all organisms.It consists of adenylosuccinate synthetase(AdSS)using inosinic acid(IMP)、L-aspartic acid(L-Asp)and guanosine triphosphate(GTP)as synthesis raw materials.S-AMP is a precursor compound for the synthesis of AMP.So far,the research results have focused on the structure and function of AdSS and adenylosuccinate lyase(ADSL).In the glucose-stimulated purine metabolic pathway,S-AMP has the function of promoting insulin secretion and reversing β-cell dysfunction in T2D.Therefore,S-AMP may be used as a lead compound for the improvement of disorders of glucose and lipid metabolism.At present,there are few studies on the mechanism of S-AMP and the large-scale synthesis of S-AMP.Only Sigma has sold 96%pure of S-AMP(now discontinued).In order to ensure the enough raw materials for S-AMP drug-making research,firstly,it is necessary to achieve a low-cost mass production of S-AMP.This study achieved the small-scale synthesis of S-AMP using AdSS derived from the thermophilic archaea Pyrococcus horikoshii OT3 as a catalyst.After purification,a single crystal of S-AMP was obtained,its purity was 94%,and the recovery rate was 17%by ultraviolet spectrophotometry.The results of this study provided an important reference for the establishment of a low-cost production line for S-AMP.S-AMP is one of the structural analogs of AMP and may have pharmacological activity to activate AMPK to improve the disorder of glycolipid metabolism,but related researches have not been reported.In order to verify this conjecture,I conducted a pharmacological study of S-AMP.Using the cellulose hepatoma cell line HepG2,we used the AMP as a control to study the mechanism of S-AMP activation of AMPK and improvement of glucose and lipid metabolism disorder.We found differences in the mechanisms of action of S-AMP and AMP in the AMPK signaling pathway,that is,S-AMP can up-regulate the expression of PFKFB3 to increase fatty acid decomposition activity,but AMP does not have this function.Considering the S-AMP activated glycolytic pathway,we guessed that S-AMP may directly form a complex with AMPK.The structure of this complex and AMPK-AMP complex is different,which leads to AMP can not activate glucose decomposition pathway and S-AMP may activate glucose metabolism pathway.This conjecture can be verified by SPR.This study first discovered the molecular pharmacology function of S-AMP,filling in the relevant research gaps.Combined with the existing papers,it is proved that S-AMP has the potential to develop new drugs for improving the disorder of glycolipid metabolism,it provides a new direction for the development of new drugs to improve the related diseases of glucose and lipid metabolism disorders.