1.  UREA CYCLE

This cycle is known as Krebs-Henseleit urea cycle. As ornithine is the first member of the reaction sequences, it is also called as Ornithine cycle. The 2 nitrogen atoms of urea are derived from two nitrogen atoms of urea are derived from two different sources, one from ammonia and the other directly from aspartic acid

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Step 1: Formation of Carbamoyl Phosphate

One molecule of ammonia condenses with Co2 in the presence of 2 molecules of ATP to form carbamoyl phosphate. The reaction is catalyzed by the mitichondrial enzyme carbamoyl phosphate synthetase I (CPS I)

Step 2: Formation of Citrulline

The carbamoyl group is transferred to the NH2 group of ornithine. Citrulline is neither present in tissue proteins nor in blood, but it is present in milk

Step 3: Formation of Argininosuccinate

One molecule of aspartic acid is added, which provide the 2nd nitrogen atom of urea. This needs hydrolysis of ATP to AMP level, so two  high energy phosphate bonds are utilized.

Step 4: Formation of Arginine

Argininosuccinate is cleaved to arginine and fumarate. The 3rd and 4th steps taken together may be summarized as:
Citrulline + aspartate            >>            arginine + fumarate

Step 5: Formation of urea
The final reaction of the cycle is the hydrolysis of arginine to urea and ornithine by arginase. Ornithine may be consideredas a catalyst which enters the reaction and is regenerated.

Regulation of urea cycle:

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1.  During starvation, the activity of urea cycle enzymes is elevated to meet the increased rate of protein catabolism
2.  The major regulatory step is catalyzed by CPS I where the positive effector is N acetyl glutamate(NAG)

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Disorders of urea cycle:

DISEASES	ENZYME DEFICIT
Hyperammonemia type I	CPS I
Hyperammonemia type II	Ornithine transcarbamoylase
Hyperornithinemia	Defective ornithine transporter protein
Citrullinemia	Argininosuccinate synthetase
Argininosuccinic aciduria	Argininosuccinate lyase
Hyperargininemia	Arginase