Thiamine triphosphate: a ubiquitous molecule in search of a physiological role

Abstract

Thiamine triphosphate (ThTP) was discovered over 60 years ago and it was long thought to be a specifically neuroactive compound. Its presence in most cell types, from bacteria to mammals, would suggest a more general role but this remains undefined. In contrast to thiamine diphosphate (ThDP), ThTP is not a coenzyme. In E. coli cells, ThTP is transiently produced in response to amino acid starvation, while in mammalian cells, it is constitutively produced at a low rate. Though it was long thought that ThTP was synthesized by a ThDP:ATP phosphotransferase, more recent studies indicate that it can be synthesized by two different enzymes: (1) adenylate kinase 1 in the cytosol and (2) FoF1-ATP synthase in brain mitochondria. Both mechanisms are conserved from bacteria to mammals. Thus ThTP synthesis does not seem to require a specific enzyme. In contrast, its hydrolysis is catalyzed, at least in mammalian tissues, by a very specific cytosolic thiamine triphosphatase (ThTPase), controlling the steady-state cellular concentration of ThTP. In some tissues where adenylate kinase activity is high and ThTPase is absent, ThTP accumulates, reaching ≥ 70% of total thiamine, with no obvious physiological consequences. In some animal tissues, ThTP was able to phosphorylate proteins, and activate a high-conductance anion channel in vitro. These observations raise the possibility that ThTP is part of a still uncharacterized cellular signaling pathway. On the other hand, its synthesis by a chemiosmotic mechanism in mitochondria and respiring bacteria might suggest a role in cellular energetics.

Several Polyphosphate Kinase 2 Enzymes Catalyse the Production of Adenosine 5′‐Polyphosphates

“…It has been postulated that thiamine triphosphate is a signalling molecule produced in response to nutritional changes. Like thiamine triphosphate, nucleoside 5′‐polyphosphates are present in many tissues and in many organisms, thus suggesting a basic metabolic function of these more highly phosphorylated derivatives . In general, nucleoside 5′‐polyphosphates seem to be important for cell‐signalling processes.…”

“…In general, nucleoside 5′‐polyphosphates seem to be important for cell‐signalling processes. In mammals they are known to be highly potent vasoconstrictive substances, whereas in bacteria their role has not yet been clearly identified. PPK2 enzymes, which have so far only been described in bacteria, might be involved in the regulation of AP 4 homeostasis.…”

Non‐coenzyme role of vitamin B1 in RANKL‐induced osteoclastogenesis and ovariectomy induced osteoporosis

“…After that ThDP can be phosphorylated to thiamine triphosphate (ThTP) 18 . Among the total thiamine, its derivative form of ThDP is the most abundant, accounting for 80% to 90%, while ThTP and the other forms of derivatives account for 5% to 15% 19 . ThDP is regarded as co‐factors for several pivotal metabolic enzymes.…”

Molecular profiling of foxtail millet (Setaria italica(L.) P. Beauv) from Central Himalayan Region for genetic variability and nutritional quality

“…Thiamine, also known as vitamin B 1 , is essential for energy metabolism (Bettendorff et al , 2014). Thiamine deficiency is uncommon in economically developed regions due to diversified diets and thiamine fortification of grains (Nathoo et al , 2005; Dwyer et al , 2015); however, severe thiamine deficiency leading to beriberi does occur in areas where dietary sources of thiamine are limited, such as Southeast Asia (Khounnorath et al , 2011; Coats et al , 2012).…”