The Urea Cycle

Disruptions in the urea cycle and cancer

Cancer cells rewire their metabolism to sustain rapid growth and proliferation. This includes alterations in the urea cycle, a crucial metabolic pathway for nitrogen metabolism and ammonia detoxification.

Cancer cells often alter urea cycle enzymes to increase nitrogen availability for biosynthetic processes, which supports their proliferation. Dysregulation of the urea cycle can also lead to an accumulation of ammonia, which further enhances glycolysis through mechanisms like lactate dehydrogenase A (LDHA) activation. This connection highlights how metabolic reprogramming in cancer fuels both energy production and biosynthesis, aiding in tumor growth.

The Urea Cycle

The urea cycle comprises five enzymes that convert ammonia and carbon dioxide into urea, facilitating nitrogen waste removal from the body.

Carbamoyl phosphate synthetase (CPS) is the rate-limiting enzyme in the urea cycle, partially regulated by HIF-1, a transcription factor often implicated in cancer development.

The urea cycle is interconnected with the citric acid cycle, a central hub of cellular metabolism.

Hormones like insulin and glucagon influence urea cycle enzyme activity.