Biogenesis of Hydrogen Sulfide and Thioethers by Cystathionine Beta-Synthase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10366186" target="_blank" >RIV/00216208:11110/18:10366186 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/18:10366186

Výsledek na webu

<a href="http://dx.doi.org/10.1089/ars.2017.7009" target="_blank" >http://dx.doi.org/10.1089/ars.2017.7009</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1089/ars.2017.7009" target="_blank" >10.1089/ars.2017.7009</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Biogenesis of Hydrogen Sulfide and Thioethers by Cystathionine Beta-Synthase

Popis výsledku v původním jazyce

Aims: The transsulfuration pathway enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase are thought to be the major source of hydrogen sulfide (H2S). In this study, we assessed the role of CBS in H2S biogenesis. Results: We show that despite discouraging enzyme kinetics of alternative H2S-producing reactions utilizing cysteine compared with the canonical condensation of serine and homocysteine, our simulations of substrate competitions at biologically relevant conditions suggest that cysteine is able to partially compete with serine on CBS, thus leading to generation of appreciable amounts of H2S. The leading H2S-producing reaction is condensation of cysteine with homocysteine, while cysteine desulfuration plays a dominant role when cysteine is more abundant than serine and homocysteine is limited. We found that the serine-to-cysteine ratio is the main determinant of CBS H2S productivity. Abundance of cysteine over serine, for example, in plasma, allowed for up to 43% of CBS activity being responsible for H2S production, while excess of serine typical for intracellular levels effectively limited such activity to less than 1.5%. CBS also produced lanthionine from serine and cysteine and a third of lanthionine coming from condensation of two cysteines contributed to the H2S pool. Innovation: Our study characterizes the H2S-producing potential of CBS under biologically relevant conditions and highlights the serine-to-cysteine ratio as the main determinant of H2S production by CBS in vivo. Conclusion: Our data clarify the function of CBS in H2S biogenesis and the role of thioethers as surrogate H2S markers.

Název v anglickém jazyce

Biogenesis of Hydrogen Sulfide and Thioethers by Cystathionine Beta-Synthase

Popis výsledku anglicky

Aims: The transsulfuration pathway enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase are thought to be the major source of hydrogen sulfide (H2S). In this study, we assessed the role of CBS in H2S biogenesis. Results: We show that despite discouraging enzyme kinetics of alternative H2S-producing reactions utilizing cysteine compared with the canonical condensation of serine and homocysteine, our simulations of substrate competitions at biologically relevant conditions suggest that cysteine is able to partially compete with serine on CBS, thus leading to generation of appreciable amounts of H2S. The leading H2S-producing reaction is condensation of cysteine with homocysteine, while cysteine desulfuration plays a dominant role when cysteine is more abundant than serine and homocysteine is limited. We found that the serine-to-cysteine ratio is the main determinant of CBS H2S productivity. Abundance of cysteine over serine, for example, in plasma, allowed for up to 43% of CBS activity being responsible for H2S production, while excess of serine typical for intracellular levels effectively limited such activity to less than 1.5%. CBS also produced lanthionine from serine and cysteine and a third of lanthionine coming from condensation of two cysteines contributed to the H2S pool. Innovation: Our study characterizes the H2S-producing potential of CBS under biologically relevant conditions and highlights the serine-to-cysteine ratio as the main determinant of H2S production by CBS in vivo. Conclusion: Our data clarify the function of CBS in H2S biogenesis and the role of thioethers as surrogate H2S markers.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/NV16-30384A" target="_blank" >NV16-30384A: Metabolismus organických a anorganických sloučenin síry u vybraných lidských onemocnění</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Antioxidants &amp; Redox Signaling

ISSN

1523-0864

e-ISSN

—

Svazek periodika

28

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

311-323

Kód UT WoS článku

000414560200001

EID výsledku v databázi Scopus

2-s2.0-85039869142