Urea Cycle / Ornithine cycle / Krebs-Henseleit cycle

 Urea Cycle or Ornithine cycle or Krebs-Henseleit cycle

Introduction

The urea cycle also known as the Ornithine cycle or Krebs-Henseleit cycle is a cycle of biochemical reactions that produces urea (NH₂)₂CO from ammonia (NH₃). The urea cycle converts highly toxic ammonia to urea for excretion. 

This cycle was the first metabolic cycle to be discovered (Hans Krebs and Kurt Henseleit, 1932), five years before the discovery of the TCA cycle. This cycle was described in more detail later on by Ratner and Cohen. The urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys.

The entire process converts two amino groups, one from NH⁺₄ and one from aspartate, and a carbon atom from HCO⁻₃, to the relatively nontoxic excretion product urea. This occurs at the cost of four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP).

Steps of the urea cycle

The conversion from ammonia to urea happens in five main steps. The first is needed for ammonia to enter the cycle and the following four are all a part of the cycle itself. To enter the cycle, ammonia is converted to carbamoyl phosphate. The urea cycle consists of four enzymatic reactions: one mitochondrial and three cytosolic. This uses 6 enzymes.

1.     Before the urea cycle begins ammonia is converted to carbamoyl phosphate. The reaction is catalyzed by carbamoyl phosphate synthetase I and requires the use of two ATP molecules. The carbamoyl phosphate then enters the urea cycle.

2.   Carbamoyl phosphate is converted to citrulline. With catalysis by Ornithine transcarbamoylase, the carbamoyl phosphate group is donated to Ornithine and releases a phosphate group.

3.   A condensation reaction occurs between the amino group of aspartate and the carbonyl group of citrulline to form argininosuccinate. This reaction is ATP dependent and is catalyzed by argininosuccinate synthetase.

4.   Argininosuccinate is cleavaged by argininosuccinate synthetase to form  arginine and fumarate.

5.   Arginine is cleaved by arginase to form urea and Ornithine. The Ornithine is then transported back to the mitochondria to begin the urea cycle again.