[en] Long-term studies have confirmed a causal relationship between the development of neurodegenerative processes and vitamin B1 (thiamine) deficiency. However, the biochemical mechanisms underlying the high neurotropic activity of thiamine are not fully understood. At the same time, there is increasing evidence that vitamin B1, in addition to its coenzyme functions, may have non-coenzyme activities that are particularly important for neurons. To elucidate which effects of vitamin B1 in neurons are due to its coenzyme function and which are due to its non-coenzyme activity, we conducted a comparative study of the effects of thiamine and its derivative, 3-decyloxycarbonylmethyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chloride (DMHT), on selected processes in synaptosomes. The ability of DMHT to effectively compete with thiamine for binding to thiamine-binding sites on the plasma membrane of synaptosomes and to participate as a substrate in the thiamine pyrophosphokinase reaction was demonstrated. In experiments with rat brain synaptosomes, unidirectional effects of DMHT and thiamine on the activity of the pyruvate dehydrogenase complex (PDC) and on the incorporation of radiolabeled [2-14C]pyruvate into acetylcholine were demonstrated. The observed effects of thiamine and DMHT on the modulation of acetylcholine synthesis can be explained by suggesting that both compounds, which interact in cells with enzymes of thiamine metabolism, are phosphorylated and exert an inhibitory/activating effect (concentration-dependent) on PDC activity by affecting the regulatory enzymes of the complex. Such effects were not observed in the presence of structural analogues of thiamine and DMHT without a 2-hydroxyethyl substituent at position 5 of the thiazolium cycle. The effect of DMHT on the plasma membrane Ca-ATPase was similar to that of thiamine. At the same time, DMHT showed high cytostatic activity against neuroblastoma cells.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Parkhomenko, Yu M ; Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 01054, Ukraine. Electronic address: yupark@biochem.kiev.ua
Vovk, A I; Department of Bioorganic Mechanisms, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, 02094, Ukraine
Protasova, Z S; Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 01054, Ukraine
Pylypchuk, S Yu; Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 01054, Ukraine
Chorny, S A; Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 01054, Ukraine
Pavlova, Oleksandra ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique ; Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 01054, Ukraine
Mejenska, O A; Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 01054, Ukraine
Chehovska, L I; Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 01054, Ukraine
Stepanenko, S P; Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 01054, Ukraine
Language :
English
Title :
Thiazolium salt mimics the non-coenzyme effects of vitamin B1 in rat synaptosomes.
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