The Urea Cycle

Disruptions in the urea cycle and cancer

Hypoxia fundamentally reprograms the urea cycle (UC) via HIF-driven transcriptional and post-transcriptional mechanisms. This rewiring affects growth and survival. UC suppression frees up biosynthetic precursors at the expense of ammonia clearance, allowing moderate sub-toxic ammonia to fuel growth pathways.

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.