半胱氨酸在细胞生物合成、酶催化和氧化还原代谢中发挥着重要作用。细胞内半胱氨酸库可以通过半胱氨酸的摄取或通过丝氨酸和同型半胱氨酸的新生合成来维持。在肿瘤形成期间，需要半胱氨酸来生成谷胱甘肽以应对氧化应激。虽然培养细胞已被证明对来自外源性半胱氨酸的增殖和存活高度依赖，但各种组织在体内的半胱氨酸获取和利用方式尚未得到表征。我们使用稳定同位素13C1-丝氨酸和13C6-半胱氨酸追踪全面探究了小鼠正常组织和由它们产生的癌症中的半胱氨酸代谢。在正常肝脏和胰腺中，新生半胱氨酸合成最高，而在肺组织中缺乏合成，而在肿瘤形成期间，半胱氨酸合成要么不活跃，要么被下调。相比之下，半胱氨酸的摄取和代谢成为正常组织和肿瘤的普遍特征。然而，从半胱氨酸中生成谷胱甘肽的标记在不同的肿瘤类型中有明显差异。因此，半胱氨酸是肿瘤中半胱氨酸库的主要贡献者，并且谷胱甘肽代谢在不同的肿瘤类型中具有差异。

Cysteine plays critical roles in cellular biosynthesis, enzyme catalysis, and redox metabolism. The intracellular cysteine pool can be sustained by cystine uptake or de novo synthesis from serine and homocysteine. Demand for cysteine is increased during tumorigenesis for generating glutathione to deal with oxidative stress. While cultured cells have been shown to be highly dependent on exogenous cystine for proliferation and survival, how diverse tissues obtain and use cysteine in vivo has not been characterized. We comprehensively interrogated cysteine metabolism in normal murine tissues and cancers that arise from them using stable isotope 13C1-serine and 13C6-cystine tracing. De novo cysteine synthesis was highest in normal liver and pancreas and absent in lung tissue, while cysteine synthesis was either inactive or downregulated during tumorigenesis. By contrast, cystine uptake and metabolism to downstream metabolites was a universal feature of normal tissues and tumors. However, differences in glutathione labeling from cysteine were evident across tumor types. Thus, cystine is a major contributor to the cysteine pool in tumors, and glutathione metabolism is differentially active across tumor types.