Update on Thiamine Triphosphorylated Derivatives and Metabolizing Enzymatic Complexes

Abstract

While the cellular functions of the coenzyme thiamine (vitamin B1) diphosphate (ThDP) are well characterized, the triphosphorylated thiamine derivatives, thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), still represent an intriguing mystery. They are present, generally in small amounts, in nearly all organisms, bacteria, fungi, plants, and animals. The synthesis of ThTP seems to require ATP synthase by a mechanism similar to ATP synthesis. In E. coli, ThTP is synthesized during amino acid starvation, while in plants, its synthesis is dependent on photosynthetic processes. In E. coli, ThTP synthesis probably requires oxidation of pyruvate and may play a role at the interface between energy and amino acid metabolism. In animal cells, no mechanism of regulation is known. Cytosolic ThTP levels are controlled by a highly specific cytosolic thiamine triphosphatase (ThTPase), coded by thtpa, and belonging to the ubiquitous family of the triphosphate tunnel metalloenzymes (TTMs). While members of this protein family are found in nearly all living organisms, where they bind organic and inorganic triphosphates, ThTPase activity seems to be restricted to animals. In mammals, THTPA is ubiquitously expressed with probable post-transcriptional regulation. Much less is known about the recently discovered AThTP. In E. coli, AThTP is synthesized by a high molecular weight protein complex from ThDP and ATP or ADP in response to energy stress. A better understanding of these two thiamine derivatives will require the use of transgenic models.

Follow‐up of the re‐evaluation of sulfur dioxide (E 220), sodium sulfite (E 221), sodium bisulfite (E 222), sodium metabisulfite (E 223), potassium metabisulfite (E 224), calcium sulfite (E 226), calcium bisulfite (E 227) and potassium bisulfite (E 228)

“…Gangolf et al (2010) reported that TTP is found mainly in brain mitochondria. TTP could thus be pivotal in thiamine deficiency neurotoxicity, but this has not been investigated (see for example Bettendorff, 2021).…”

B vitamin supply in plants and humans: the importance of vitamer homeostasis

“…The thiamine unit can carry between one and three phosphate moieties, thiamine monophosphate (TMP), thiamine diphosphate (TDP) or thiamine triphosphate (TTP), respectively, which can in turn be adenosylated. However, only adenosine TDP (ATDP) and adenosine TTP (ATTP) have been reported (Bettendorff, 2021).…”

“…Beyond the coenzyme role in energy metabolism, additional roles for B 1 vitamers have been proposed. In the nervous system of animals, TTP has been implicated in chloride channel regulation, membrane excitability, nerve conduction and neurotransmitter release (Bettendorff, 2021). Furthermore, TTP was also described to phosphorylate rapsyn (a membrane protein that binds acetylcholine receptors); however, the physiological significance of this process remains unknown (Nghiem et al., 2000).…”

Sulfite-Catalyzed Nucleophilic Substitution Reactions with Thiamin and Analogous Pyrimidine Donors Proceed via an SNAE Mechanism

“…Thiamin ( 1 ), also known as vitamin B 1 , is an essential cofactor utilized by all domains of life. , The pyrophosphorylated form of thiamin is required for the activity of several enzymes involved in the metabolism of carbohydrates and amino acids, including transketolase in the pentose phosphate pathway, α-ketoglutarate dehydrogenase in the citric acid cycle, and pyruvate dehydrogenasethe critical enzyme connecting glycolysis to the citric acid cycle . Several non-cofactor functions for thiamin have also been reported. − …”