Urea Cycle

🪶The urea cycle eliminates nitrogenous waste, primarily ammonia, produced during protein metabolism.

🪶The liver synthesizes urea 80-90% then transported to the kidneys for excretion in urine.

🪶The Krebs-Henseleit cycle, the first discovered metabolic cycle.

🪶Urea (NH2)2CO contains two amino groups, one from ammonia (NH3) and one from aspartate.

🪶CO2 supplies carbon skeletons for urea synthesis.

🪶Urea synthesis occurs in five enzymatic reactions.

🪶Enzyme Location:

The first two enzymes reside in the mitochondria, while the remaining three are cytosolic.

Urea cycle describes in detail as below:-

🪶Carbamoyl Phosphate Synthesis:

Mitochondrial enzyme CPS I catalyzes the formation of carbamoyl phosphate from CO2, ammonia, and ATP.

🪶This irreversible, rate-limiting step requires N-acetylglutamate for activation.

🪶Cyptosolic CPS II, involved in pyrimidine synthesis accept of amino group for glutomine, does not require N-acetylglutamate for activity.

2.Formation of Citrulline:

💫Citrulline is synthesized from carbamoyl phosphate and ornithine by ornithine transcarbamoylase in the urea cycle.

💫Ornithine is regenerated and reused in the urea cycle.

3.Synthesis of Argininosuccinate:

💫Argininosuccinate synthase condenses citrulline with aspartate to form argininosuccinate.

💫The second amino group of aspartic acid is incorporated into argininosuccinate in this step.

💫The reaction requires ATP, which is cleaved into AMP and pyrophosphate (PPi).

💫The latter is further broken down into inorganic phosphate (Pi).

4.Cleavage of Argininosuccinate:

🦨Argininosuccinase cleaves argininosuccinate to yield arginine and fumarate.

🦨Arginine is the immediate precursor for urea synthesis.

🦨Fumarate released here provides a link between the urea cycle and the TCA cycle and gluconeogenesis.

5.Formation of Urea:

🦨Arginase is the enzyme that cleaves arginine to yield urea and ornithine.

🦨Ornithine is regenerated and transported back to the mitochondria for its role in the urea cycle.

🦨Arginase is activated by cobalt and Mn2+.

🦨Arginase is mainly found in the liver, while the rest of the enzymes of the urea cycle are also present in other tissues.

🦨Due to this, arginine synthesis may occur in various organs, but only the liver produces urea.

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