Journal
BIOMOLECULES
Volume 11, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/biom11111645
Keywords
thiamine triphosphate; adenosine thiamine triphosphate; thiamine triphosphatase; adenylate kinase; CYTH; triphosphate tunnel metalloenzymes; thiamine diphosphokinase; ATP synthase; thiamine diphosphate; glutamate dehydrogenase
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ThTP and AThTP, two thiamine derivatives, exist in small amounts in various organisms and have different synthesis mechanisms and dependencies. ThTP is synthesized through ATP synthase, while AThTP can be synthesized by a high molecular weight protein complex from ThDP and ATP or ADP under energy stress.
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.
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