Pyruvate carboxylase (PC) is a mitochondrial enzyme that catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate (OAA), serving to replenish the tricarboxylic acid (TCA) cycle. In nonmalignant tissue, PC plays an essential role in controlling whole-body energetics through regulation of gluconeogenesis in the liver, synthesis of fatty acids in adipocytes, and insulin secretion in pancreatic β cells. In breast cancer, PC activity is linked to pulmonary metastasis, potentially by providing the ability to utilize glucose, fatty acids, and glutamine metabolism as needed under varying conditions as cells metastasize. PC enzymatic activity appears to be of particular importance in cancer cells that are unable to utilize glutamine for anaplerosis. Moreover, PC activity also plays a role in lipid metabolism and protection from oxidative stress in cancer cells. Thus, PC activity may be essential to link energy substrate utilization with cancer progression and to enable the metabolic flexibility necessary for cell resilience to changing and adverse conditions during the metastatic process.

中文翻译：

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丙酮酸羧化酶和癌症进展

丙酮酸羧化酶 (PC) 是一种线粒体酶，可催化 ATP 依赖性丙酮酸羧化为草酰乙酸 (OAA)，用于补充三羧酸 (TCA) 循环。在非恶性组织中，PC 通过调节肝脏糖异生、脂肪细胞脂肪酸合成和胰腺 β 细胞胰岛素分泌，在控制全身能量方面发挥重要作用。在乳腺癌中，PC 活性可能与肺转移有关，可能是因为细胞转移时在不同条件下根据需要利用葡萄糖、脂肪酸和谷氨酰胺代谢的能力。PC 酶活性似乎对于无法利用谷氨酰胺进行回补的癌细胞特别重要。此外，PC 活性还在脂质代谢和保护癌细胞免受氧化应激方面发挥作用。因此，PC活性对于将能量底物利用与癌症进展联系起来以及使细胞在转移过程中适应变化和不利条件所需的代谢灵活性至关重要。