UREA CYCLE MADE EASY 2020 - METABOLISMS MADE SIMPLE

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The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea from ammonia. This cycle occurs in ureotelic organisms. 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.

Amino acid catabolism results in waste ammonia. All animals need a way to excrete this product. Most aquatic organisms, or ammonotelic organisms, excrete ammonia without converting it.[1] Organisms that cannot easily and safely remove nitrogen as ammonia convert it to a less toxic substance such as urea or uric acid via the urea cycle, which occurs mainly in the liver. Urea produced by the liver is then released into the bloodstream where it travels to the kidneys and is ultimately excreted in urine.
Steps of the urea cycle:

Carbamoyl phosphate is converted to citrulline. With catalysis by ornithine transcarbamoylase, the carbamoyl phosphate group is donated to ornithine and releases a phosphate group.
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.
Argininosuccinate undergoes cleavage by argininosuccinase to form arginine and fumarate.
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.

Regulation:

N-Acetylglutamic acid(NAG)
The synthesis of carbamoyl phosphate and the urea cycle are dependent on the presence of N-acetylglutamic acid (NAcGlu), which allosterically activates CPS1. NAcGlu is an obligate activator of carbamoyl phosphate synthetase. Synthesis of NAcGlu by N-acetylglutamate synthase (NAGS) is stimulated by both Arg, allosteric stimulator of NAGS, and Glu, a product in the transamination reactions and one of NAGS's substrates, both of which are elevated when free amino acids are elevated. So Glu not only is a substrate for NAGS but also serves as an activator for the urea cycle.