The Urea Cycle: Nitrogen Metabolism and Waste Excretion

The urea cycle, also known as the ornithine cycle, is a critical metabolic pathway that primarily occurs in the liver, and to a lesser extent, in the kidneys. Its main function is to convert excess nitrogen from protein and amino acid breakdown into urea, a less toxic compound than ammonia, for safe excretion in urine.

Steps in the Urea Cycle

The urea cycle involves several enzymatic reactions within the mitochondria and cytoplasm of liver cells. Key molecules include ammonia, carbon dioxide, ornithine, citrulline, argininosuccinate, and arginine.

1. Formation of Carbamoyl Phosphate

• Ammonia (NH₃) and carbon dioxide (CO₂) combine in the mitochondria.
• This reaction, catalyzed by carbamoyl phosphate synthetase I (CPS I), produces carbamoyl phosphate.

2. Formation of Citrulline

• Carbamoyl phosphate reacts with ornithine, catalyzed by ornithine transcarbamylase (OTC), to form citrulline.
• Ornithine is released and can re-enter the mitochondria for another cycle.

3. Formation of Argininosuccinate

• Citrulline moves from the mitochondria to the cytoplasm.
• Citrulline and aspartate combine in the cytoplasm, catalyzed by argininosuccinate synthetase, to form argininosuccinate.

4. Formation of Arginine

• Argininosuccinate is cleaved by argininosuccinate lyase, producing fumarate and arginine.

5. Formation of Urea

• Arginine is hydrolyzed by arginase, releasing urea and regenerating ornithine.
• Urea, being water-soluble and less toxic than ammonia, is suitable for urine excretion.

Urea Excretion and Cycle Significance

Urea travels from the liver to the kidneys through the bloodstream, where it is filtered and excreted in urine. The urea cycle is essential for maintaining nitrogen balance and preventing toxic ammonia buildup. Urea cycle disorders can cause hyperammonemia, a condition with elevated blood ammonia levels, potentially harming the central nervous system.