Krebs-Henseleit Cycle MCQ - Practice Questions with Answers

• Ammonia is converted to urea in the hepatocytes of the liver in five steps via urea cycle- in the mitochondria (first 2 steps) and cytosol (last 3 steps). 
• The urea then travels through the bloodstream to the kidney and is excreted in the urine.
• The urea cycle was discovered by Hans Krebs (who also discovered Citric acid or Krebs cycle) and his student associate Kurt Henseleit in 1932. 
• Five enzymes take part in the formation of urea. Out of these the first four are found in all cells. But the last enzyme arginase is found only in the liver cells thus assuring the formation of final product urea only in the liver despite the formation of arginine in other tissues.

Steps of Urea Cycle:

1. Synthesis of carbamoyl phosphate:

• This step takes place in the mitochondria of the liver cells. 
• Here the ammonium ions react with carbon dioxide (product of mitochondrial respiration) to form carbamoyl phosphate catalyzed by the enzyme carbamoyl phosphate synthetase I. 
• This is an irreversible, rate-limiting, ATP-dependent reaction and consumes 2 ATP. 

2. Synthesis of citrulline: 

• Carbamoyl phosphate produced in the first step reacts with ornithine in the presence of ornithine transcarbamoylase to synthesize citrulline. 
• Just like oxaloacetate in the Krebs cycle, ornithine plays a similar role acting as accepting substrate at each turn of the cycle. 
• Via a transporter system, this citrulline is now transferred to the cytosol of the liver cells.

3. Formation of argininosuccinate:

• In this ATP dependent step, the carbonyl carbon of citrulline is attacked by the lone pair of the amine in aspartate to produce argininosuccinate in presence of argininosuccinate synthetase. 
• In this step, the second nitrogen of urea is incorporated by condensation.
• ATP is broken down into AMP and pyrophosphate.

4. Breakdown of argininosuccinate:

• Arginosuccinase promotes the cleavage of argininosuccinate to give arginine and fumarate in a reversible manner. 
• Fumarate formed here joins the citric acid cycle forming a link between urea and citric acid cycle.

5. Formation of urea:

• Arginine produced in the earlier step is broken down by arginase to give urea and ornithine. 
• Ornithine is recycled back to the mitochondria for the next cycle.