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Thiamin-dependent enzymes: new perspectives from the interface between chemistry and biologyстатья
Информация о цитировании статьи получена из
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 4 декабря 2023 г.
- Автор: Bunik V.
- Журнал: FEBS Journal
- Том: 280
- Год издания: 2013
- Издательство: Blackwell Publishing Inc.
- Местоположение издательства: United Kingdom
- DOI: 10.1111/febs.12589
- Аннотация: Thiamin (vitamin B1) is essential for life and health. Insufficient levels of thiamin cause neurological and metabolic disorders which may be corrected by thiamin administration. Beneficial effects of thiamin have also been observed in Alzheimer’s and Parkinson’s patients. However, the long-established view of the molecular mechanisms underlying the therapeutic effects of thiamin overlooks important new achievements in the field of thiamin biochemistry, thus hindering discoveries of new pharmacological treatments. This minireview series highlights contemporary studies on the molecular mechanisms of action of thiamin and its natural derivatives and their implications for addressing a number of current challenges. Thiamin-dependent enzymes include the enzymes of thiamin metabolism and those dependent on the action of thiamin diphosphate (ThDP) as a coenzyme. The ThDP-dependent enzymes have long been investigated from both chemical and biological viewpoints. The synthesis of thiamin analogs as mechanistic probes and the part played by thiamin in enzyme catalysis were described in earlier minireview series (FEBS Journal (2009), 276 2431–2468 and 2893-2925). Scientific benefits and perspectives gained from the knowledge transfer between studies on the thiamin chemistry and biology is the focus of the current minireview series. Deep understanding of the details of catalytic mechanisms is key for engineering of enzymes in developing environmentally friendly technology for bioorganic synthesis. Versatility and performance of biological systems greatly helps to achieve this goal. This is covered in the minireviews by Hailes et al. and Andrews & McLeish. Details of the catalytic mechanism are also important for medicine as, with this knowledge, enzyme-specific compounds may be generated that can be used to control metabolic fluxes, model impaired function of enzymes in diseases or fight pathogens, as discussed in the minireview by Bunik et al. Two minireviews (Bunik et al. and Bettendorff & Wins) draw attention to the thiamin-dependent enzymes that control the levels of the non-coenzyme derivatives of thiamin. The concerted generation of triphosphorylated and adenylated thiamin derivatives in response to metabolic stress suggests that these compounds are involved in homeostatic regulation. These data, along with the ThDP-riboswitch action, add strong new arguments in favour of the significance of the non-coenzyme action of thiamin. Although the thiamin participation in biological processes beyond the ThDP-dependent metabolic reactions has been known about since the 1930s, there is still a gap in the identification and molecular characterization of the enzymes responsible for metabolism of the non-coenzyme derivatives of thiamin. In general, high ADP/ThDP ratios existing in vivo argue against biological relevance of the suggested thiamin triphosphate synthesis by the ADP-dependent enzymes adenylate kinase and F1Fo ATP synthase. Hence, thiamin-specific enzymes dealing with the non-coenzyme derivatives of thiamin remain to be identified. The only well-characterized representative of such enzymes is thiamin triphosphatase, whose structural features, catalytic mechanism and CYTH family relationship are considered in the review by Bettendorff & Wins. The data highlighted in this minireview series should stimulate discrimination between the sites in enzymes and other potential targets that bind the coenzyme (ThDP) and non-coenzyme (triphosphorylated and adenylated) derivatives of thiamin. Site-specific analogs of thiamin may thus be developed and used to identify proteins and pathways dependent on the non-coenzyme derivatives of thiamin. Addressing this challenge should allow us to decipher the many actions of thiamin in living systems, opening new ways to metabolic regulation and disease treatments.
- Добавил в систему: Буник-Фаренвальд Виктория-Лариса Ивановна