The Quantitative Significance of the Transsulfuration Enzymes for H2S Production in Murine Tissues
The Quantitative Significance of the Transsulfuration Enzymes for H2S Production in Murine Tissues
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DOI：
10.1089/ars.2010.3781
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发表时间：
2011-07-15
影响因子：
6.6
通讯作者：
Banerjee, Ruma
中科院分区：
文献类型：
--
作者：
Kabil, Omer;Vitvitsky, Victor;Banerjee, Ruma
硫代转化途径中的酶，半胱硫氨酸β合成酶（CBS）和半胱硫氨酸γ -裂解酶（CSE），对于气体信号分子硫化氢（H2S）的内源性生成非常重要。CBS和CSE对不同组织中H2S生成的相对贡献尚不清楚。在这项研究中，我们报告了小鼠肝脏和肾脏中CBS和CSE的定量，以及它们在饱和底物浓度下对这些组织和大脑中H2S生成的贡献。结果表明，CBS蛋白水平显著低于CSE；肝脏和肾脏分别是60倍和20倍。每种酶在肝脏中的含量均高于肾脏，CBS和CSE的含量分别是肾脏的2倍和6倍。在高底物浓度（每种半胱氨酸和同型半胱氨酸各20毫米）下，CBS和CSE的肝脏H2S生产能力大致相等，而在肾脏和大脑中，CBS是H2S的主要来源，分别占总产量的80%和95%。在生理相关的底物浓度下，并根据CBS与CSE水平的差异进行调整，我们估计CBS仅占肝脏转硫途径酶产生H2S的3%。Antioxid。机械工程学报，36(5):363-372。
The enzymes of the transsulfuration pathway, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), are important for the endogenous production of hydrogen sulfide (H2S), a gaseous signaling molecule. The relative contributions of CBS and CSE to H2S generation in different tissues are not known. In this study, we report quantification of CBS and CSE in murine liver and kidney and their contribution to H2S generation in these tissues and in brain at saturating substrate concentrations. We show that CBS protein levels are significantly lower than those of CSE; 60-fold and 20-fold in liver and kidney, respectively. Each enzyme is more abundant in liver compared with kidney, twofold and sixfold for CBS and CSE, respectively. At high substrate concentrations (20 mM each cysteine and homocysteine), the capacity for liver H2S production is approximately equal for CBS and CSE, whereas in kidney and brain, CBS constitutes the major source of H2S, accounting for similar to 80% and similar to 95%, respectively, of the total output. At physiologically relevant concentrations of substrate, and adjusting for the differences in CBS versus CSE levels, we estimate that CBS accounts for only 3% of H2S production by the transsulfuration pathway enzymes in liver. Antioxid. Redox Signal. 15, 363-372.