由于白蛋白水平降低和脂肪酸氧化以及脂肪酸合成和脂肪分解增加，血浆非酯化脂肪酸（NEFA）在癌症中升高。白蛋白消耗和 NEFA 升高最大限度地释放白蛋白结合色氨酸 (Trp) 并增加其沿犬尿氨酸途径的流量，导致促炎犬尿氨酸代谢物的产生增加，肿瘤利用这些代谢物破坏 T 细胞功能并实现免疫逃逸。犬尿酸激活芳基烃受体可促进吲哚胺 2,3-双加氧酶对肝外色氨酸的降解，并导致聚（ADP-核糖）聚合酶上调，从而激活该酶以及 SIRT1（沉默交配型信息调节 2 同源物 1）可能导致 NAD 和 ATP 耗尽，导致细胞死亡。 NEFA 还调节血红素合成和降解，这些变化会影响同型半胱氨酸代谢以及还原型谷胱甘肽和硫化氢的产生。血红素和同型半胱氨酸代谢之间相互作用在癌症生物学中的重要性很少受到关注。建议针对癌症中的色氨酸处置来预防 NEFA 效应。版权所有 © 2024。由 Elsevier B.V. 出版。

Plasma nonesterified fatty acids (NEFA) are elevated in cancer, because of decreased albumin levels and of fatty acid oxidation, and increased fatty acid synthesis and lipolysis. Albumin depletion and NEFA elevation maximally release albumin-bound tryptophan (Trp) and increase its flux down the kynurenine pathway, leading to increased production of proinflammatory kynurenine metabolites, which tumors use to undermine T-cell function and achieve immune escape. Activation of the aryl hydrocarbon receptor by kynurenic acid promotes extrahepatic Trp degradation by indoleamine 2,3-dioxygenase and leads to upregulation of poly (ADP-ribose) polymerase, activation of which and also of SIRT1 (silent mating type information regulation 2 homolog 1) could lead to depletion of NAD+ and ATP, resulting in cell death. NEFA also modulate heme synthesis and degradation, changes in which impact homocysteine metabolism and production of reduced glutathione and hydrogen sulphide. The significance of the interactions between heme and homocysteine metabolism in cancer biology has received little attention. Targeting Trp disposition in cancer to prevent the NEFA effects is suggested.Copyright © 2024. Published by Elsevier B.V.