How is urea regulated?

Urea cycle regulation is dependent on dietary factors and hormone concentrations (1). A feed-forward regulation exists in that available ammonia causes more urea to be created (1). This can also mean that higher protein can also act as a feed-forward regulation since it increases urea enzyme levels (1-2). Ammonia can come from diet, from deamination, or bacteria in the GI tract inducing formation of carbamoyl phosphate by mitochondrial carbamoyl phosphate synthetase (1).

Other regulation also exists. First, synthesis of n-acetyl glutamate, which is the allosteric activator of the carbamoyl phosphate synthetase (2). The activator is made in the liver and intestine when stimulated by available arginine (1-2). Second, arginase is inhibited by ornithine and lysine making it able to become rate limiting (1).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Lieberman M, Marks A, Smith CM, Marks DB. Marks’ basic medical chemistry, ed 3. Lippincott Williams & Wilkins, 2008.

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