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Purinergic signaling in leishmaniasis infection

Reactome ID: R-HSA-9660826

中文名称

丙酮酸脱氢酶复合体

通路描述

丙酮酸脱氢酶复合体催化丙酮酸、辅酶 A 和 NAD+ 反应生成乙酰 CoA、CO2 和 NADH。该酶复合物包含多个 E1α、E1β、E2 和 E3 亚基,每个亚基具有不同的催化活性(Reed and Hackert 1990; Zhou et al 2001),并需要 X 亚基(PDHX)将 E3 锚定在 E2 上(Hiromasa et al., 2004; Vijayakrishnan et al., 2010)。反应始于由 E1α和E1β催化的丙酮酸的氧化脱羧。与此同时,与 E2 结合的脂酰辅酶 A 被还原。随后,来自丙酮酸的乙酰基在两个步骤中由 E2 转移至辅酶 A(DLAT,二氢脂酰转移酶)。最后,脂酰辅酶 A 的氧化形式再生,电子在两个步骤中转移给 NAD+(DLD,二氢脂酰脱氢酶)。该反应的生化细节已通过纯化的牛丙酮酸脱氢酶复合物和其他非人来源的亚基的工作得出。来自表达 E1α(Lissens et al. 2000)、E1β(Brown et al. 2004)、E2(Head et al. 2005)和 E3(Brautigam et al. 2005)突变体患者的直接证据表明,PDH 复合体中各亚基的功能。最常见的 PDH 复合体缺陷是由 PDHA 和 PDHX 缺陷引起的,但也可由复合体任何成分的缺陷引起(例如 Pavlu-Pereira et al., 2020; 综述在 Prasad et al., 2011)。
英文描述
Purinergic signaling in leishmaniasis infection The purinoreceptors are divided into inotropic (P2XR) and metabotropic (P2YR) subtypes whose ligands are the nucleotides ATP and UDP respectively (Cekic et al. 2016). The binding of these nucleotides to their receptors on macrophages have been associated with the activation of the inflammasome leading to the subsequent activation of interleukin 1 beta (IL1β) and TNF-α (Cekic et al. 2016 & Figueiredo et al. 2016). The liberation of ATP comes from tissues facing stressful stimuli such as a tissue injury or microorganism infection, amongst others. As a regulatory mechanism, certain enzymes can reduce ATP to Adenosine and a nucleoside can stimulate signalling pathways leading to the synthesis of anti-inflammatory cytokines (Cekic et al. 2016).

The activation of the receptor P2RX7 was shown to lead to the activation of killing mechanisms or cell death programs, ending up in the elimination of microbes such as Leishmania amazonensis, Mycobacterium tuberculosis, Chlamydia psittaci, and Toxoplasma gondii (Coutinho-Silva et al. 2012 & Idzko, 2014).

所含基因

25 个基因