Synthesis, physico-chemical properties and effect of adenosine thiamine triphosphate on vitamin B 1 metabolism in the liver of alloxan diabetic rats

• Published in: Biochimica et biophysica acta. General subjects 2022-04, Vol.1866 (4), p.130086
• Main Authors: Makarchikov, Alexander F, Kudyrka, Tatsiana G, Luchko, Tatyana A, Yantsevich, Aliaksei V, Rusina, Iryna M, Makar, Alena A, Kolas, Iryna K, Usanov, Sergey A
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate; Alloxan - metabolism; Animals; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Liver - metabolism; Mammals; Rats; Thiamine - metabolism; Thiamine - pharmacology; Thiamine Triphosphate; Vitamins
• ISSN: 1872-8006
• DOI: 10.1016/j.bbagen.2022.130086

Adenosine thiamine triphosphate (AThTP) is a nucleotide discovered in bacteria and some other living organisms more than a decade ago. No biochemical function for AThTP has been established yet, however, experimental data available indicate its possible involvement in metabolic regulation or cell signaling. Metabolism of AThTP in mammals, as well as the feasibility of its pharmacological application, is essentially unstudied. Preparative low-pressure chromatography was employed to purify chemically synthesized AThTP with its further analysis by mass spectrometry, HPLC, UV and fluorescence spectroscopy. Enzyme activity assays along with HPLC were used to examine the effects of AThTP and thiamine on vitamin B metabolism in the liver of alloxan-induced diabetic rats. An improved procedure for AThTP synthesis and purification is elaborated. Solution stability, optical spectral properties and the molar absorption coefficient for AThTP were determined. The levels of thiamine compounds were found to be increased in the liver of diabetic rats. Neither AThTP nor thiamine treatment affected hepatic vitamin B metabolism. Fasting blood glucose concentration was also unchangeable after AThTP or thiamine administration. Contrast to the widespread view about thiamine deficiency in diabetes, our results clearly shows an adaptive increase in the level of B vitamers in the liver of alloxan diabetic rats with no further rising after AThTP or thiamine treatment at a moderate dose. Neither AThTP nor thiamine is effective in glycaemic control. These findings are to be considered in future studies dealing with thiamine or its analogues application to correct metabolic disturbances in diabetes.