Dattilo Maurizio, Fontanarosa Carolina, Spinelli Michele, Bini Vittorio, Amoresano Angela
R&D Department, Parthenogen, Lugano, Switzerland.
Department of Chemical Sciences, University of Napoli "Federico II," Naples, Italy.
Nutr Metab Insights. 2022 Jan 7;15:11786388211065372. doi: 10.1177/11786388211065372. eCollection 2022.
Hydrogen sulfide (HS) is a pivotal gasotransmitter networking with nitric oxide (NO) and carbon monoxide (CO) to regulate basic homeostatic functions. It is released by the alternative pathways of transulfuration by the enzymes Cystathionine Beta Synthase (CBS) and Cystathionine Gamma Lyase (CSE), and by Cysteine AminoTransferase (CAT)/ 3-Mercaptopyruvate Sulfur Transferase (3MPST). A non-enzymatic, intravascular release is also in place. We retrospectively investigated the possibility to modulate the endogenous HS release and signaling in humans by a dietary manipulation with supplemented micronutrients (L-cystine, Taurine and pyridoxal 5-phopsphate/P5P).
Patients referring for antiaging purposes underwent a 10-day supplementation. Blood was collected at baseline and after treatment and the metabolome was investigated by mass spectrometry to monitor the changes in the metabolites reporting on HS metabolism and related pathways.
Data were available from 6 middle aged subjects (2 women). Micronutrients increased 3-mercaptopyruvate ( = .03), reporting on the activity of CAT that provides the substrate for HS release within mitochondria by 3MPST, decreased lanthionine ( = .024), reporting the release of HS from CBS, and had no significant effect of HS release from CSE. This is compatible with a homeostatic balancing. We also recorded a strong increase of reporters of HS-induced pathways including 5-MethylTHF ( = .001) and SAME ( = .022), reporting on methylation capacity, and of BH4 ( = .021) and BH2 ( = .028) reporting on nitric oxide metabolism. These activations may be explained by the concomitant induction of non-enzymatic release of HS.
Although the current evidences are weak and will need to be confirmed, the effect of micronutrients was compatible with an increase of the HS endogenous release and signaling within the control of homeostatic mechanisms, further endorsing the role of feeding in health and disease. These effects might result in a HS boosting effect in case of defective activity of pathologic origin, which should be checked in duly designed clinical trials.
硫化氢（HS）是一种关键的气体信号分子，与一氧化氮（NO）和一氧化碳（CO）相互作用，调节基本的稳态功能。它通过胱硫醚β合酶（CBS）和胱硫醚γ裂解酶（CSE）的转硫替代途径，以及通过半胱氨酸转氨酶（CAT）/3-巯基丙酮酸硫转移酶（3MPST）释放。还存在非酶促的血管内释放。我们回顾性研究了通过补充微量营养素（L-胱氨酸、牛磺酸和磷酸吡哆醛/P5P）进行饮食干预来调节人体内源性HS释放和信号传导的可能性。
以抗衰老为目的前来就诊的患者接受了为期10天的补充治疗。在基线和治疗后采集血液，通过质谱法研究代谢组，以监测与HS代谢及相关途径有关的代谢物变化。
有6名中年受试者（2名女性）的数据可用。微量营养素使3-巯基丙酮酸增加（P = 0.03），这反映了CAT的活性，CAT为3MPST在线粒体内释放HS提供底物；使羊毛硫氨酸减少（P = 0.024），这反映了HS从CBS的释放情况；对CSE释放HS没有显著影响。这与稳态平衡相符。我们还记录到HS诱导途径的标志物大幅增加，包括5-甲基四氢叶酸（P = 0.001）和S-腺苷甲硫氨酸（P = 0.022），反映甲基化能力；以及四氢生物蝶呤（P = 0.021）和二氢生物蝶呤（P = 0.028），反映一氧化氮代谢。这些激活可能是由于HS非酶促释放的同时诱导所致。
尽管目前的证据尚不充分且有待证实，但微量营养素的作用与在稳态机制控制下HS内源性释放和信号传导的增加相符，进一步支持了饮食在健康和疾病中的作用。在病理性起源的活性缺陷情况下，这些作用可能会导致HS增强效应，这应在适当设计的临床试验中进行检验。
