癌细胞对 L-蛋氨酸 (L-Met) 上瘾，并且由于过度的转甲基作用（称为霍夫曼效应），对 L-Met 的需求量比正常细胞大得多。通过限制 L-Met 的饮食来针对这一弱点，研究人员已经能够在抑制肿瘤生长和根除癌细胞方面取得有希望的结果。蛋氨酸酶（EC 4.4.1.11；METase）催化 L-Met 转化为 α-酮丁酸、氨和甲硫醇。 METase的使用最初由于其体内稳定性差、免疫原性高以及酶诱导的灭活抗体而受到限制。这些问题可以通过聚乙二醇化、封装在红细胞中以及各种定点诱变来部分解决。当发现 METase 可以有效口服给药时，重大突破出现了。 L-天冬酰胺酶经 FDA 批准用于治疗急性淋巴细胞白血病。由于 L-Met 成瘾是癌症的普遍和基本标志，METase 作为一种治疗方法具有更大的潜力。版权所有 © 2024。由 Elsevier B.V. 出版。

Cancer cells are addicted to L-methionine (L-Met) and have a much greater requirement for L-Met than normal cells due to excess transmethylation, termed the Hoffman effect. By targeting this vulnerability through dietary restriction of L-Met, researchers have been able to achieve promising results in inhibiting tumor growth and eradicating cancer cells. Methioninase (EC 4.4.1.11; METase) catalyzes the transformation of L-Met into α-ketobutyrate, ammonia, and methanethiol. The use of METase was initially limited due to its poor stability in vivo, high immunogenicity, and enzyme-induced inactivating antibodies. These issues could be partially resolved by PEGylation, encapsulation in erythrocytes, and various site-directed mutagenesis. The big breakthrough came when it was discovered that METase is effectively administered orally. The enzyme L-asparaginase is approved by the FDA for treatment of acute lymphoblastic leukemia. METase has more potential as a therapeutic since addiction to L-Met is a general and fundamental hallmark of cancer.Copyright © 2024. Published by Elsevier B.V.