๐ชถThe urea cycle eliminates nitrogenous waste, primarily ammonia, produced during protein metabolism.
๐ชถThe liver synthesizes urea 80-90% then transported to the kidneys for excretion in urine.
๐ชถThe Krebs-Henseleit cycle, the first discovered metabolic cycle.
๐ชถUrea (NH2)2CO contains two amino groups, one from ammonia (NH3) and one from aspartate.
๐ชถCO2 supplies carbon skeletons for urea synthesis.
๐ชถUrea synthesis occurs in five enzymatic reactions.
๐ชถEnzyme Location:
The first two enzymes reside in the mitochondria, while the remaining three are cytosolic.
Urea cycle describes in detail as below:-
๐ชถCarbamoyl Phosphate Synthesis:
Mitochondrial enzyme CPS I catalyzes the formation of carbamoyl phosphate from CO2, ammonia, and ATP.
๐ชถThis irreversible, rate-limiting step requires N-acetylglutamate for activation.
๐ชถCyptosolic CPS II, involved in pyrimidine synthesis accept of amino group for glutomine, does not require N-acetylglutamate for activity.
2.Formation of Citrulline:
๐ซCitrulline is synthesized from carbamoyl phosphate and ornithine by ornithine transcarbamoylase in the urea cycle.
๐ซOrnithine is regenerated and reused in the urea cycle.
3.Synthesis of Argininosuccinate:
๐ซArgininosuccinate synthase condenses citrulline with aspartate to form argininosuccinate.
๐ซThe second amino group of aspartic acid is incorporated into argininosuccinate in this step.
๐ซThe reaction requires ATP, which is cleaved into AMP and pyrophosphate (PPi).
๐ซThe latter is further broken down into inorganic phosphate (Pi).
4.Cleavage of Argininosuccinate:
๐ฆจArgininosuccinase cleaves argininosuccinate to yield arginine and fumarate.
๐ฆจArginine is the immediate precursor for urea synthesis.
๐ฆจFumarate released here provides a link between the urea cycle and the TCA cycle and gluconeogenesis.
5.Formation of Urea:
๐ฆจArginase is the enzyme that cleaves arginine to yield urea and ornithine.
๐ฆจOrnithine is regenerated and transported back to the mitochondria for its role in the urea cycle.
๐ฆจArginase is activated by cobalt and Mn2+.
๐ฆจArginase is mainly found in the liver, while the rest of the enzymes of the urea cycle are also present in other tissues.
๐ฆจDue to this, arginine synthesis may occur in various organs, but only the liver produces urea.
