Anabolism

Cancer

Organic chemistry

Enzyme

Chemistry

Metabolic pathway

Arginine

Urea

Nitrogen cycle

Amino acid

Nitrogen

Genetics

Biochemistry

Metabolism

Urea cycle

Biology

Cancer cell

Catabolism

Nature reviews. Cancer

Cancer cells reprogramme metabolism to maximize the use of nitrogen and carbon for the anabolic synthesis of macromolecules that are required during tumour proliferation and growth. To achieve this aim, one strategy is to reduce catabolism and nitrogen disposal. The urea cycle (UC) in the liver is the main metabolic pathway to convert excess nitrogen into disposable urea. Outside the liver, UC enzymes are differentially expressed, enabling the use of nitrogen for the synthesis of UC intermediates that are required to accommodate cellular needs. Interestingly, the expression of UC enzymes is altered in cancer, revealing a revolutionary mechanism to maximize nitrogen incorporation into biomass. In this Review, we discuss the metabolic benefits underlying UC deregulation in cancer and the relevance of these alterations for cancer diagnosis and therapy. This Review discusses the reprogramming of the urea cycle, the main metabolic liver pathway for nitrogen disposal, in cancer cells. The authors provide insight into the metabolic advantages and therapeutic opportunities stemming from urea cycle enzyme perturbations in cancer.

Rewiring urea cycle metabolism in cancer to support anabolism