L32 - Nitrogen Transport and Disposal Flashcards
What is the role of glutamate in amino acid synthesis?
Glutamate provides nitrogen for amino acid synthesis.
It transfers nitrogen by means of transamination reactions to a-keto acids to form amino acids (requires PLP as cofactor). The nitrogen is either obtained by glutamate from transamination of other amino acids or from NH4+ by means of the glutamate dehydrogenase (GDH) reaction.
One of the two forms of nitrogen (NH4+) that enters the urea cycle is released from glutamate dehydrogenase (GDH – an oxidoreductase). Where does the second come from?
Asparate, which is obtained from glutamate by transamination of oxaloacetate.
What are the major carriers of nitrogen in the blood?
**Alanine **and Glutamine
How is glutamine synthesized?
Glutamine is synthesized from glutamate by the fixation of ammonia, requiring ATP and the enzyme glutamine synthetase.
Where is glutamine synthetase found and what is its major role?
Glutamine synthetase is a cytoplasmic enzyme found in all cells. In the liver, it is located in cells surrounding the portal vein, and its major role is to convert any ammonia that has escaped from urea production into glutamine so that free ammonia does not leave the liver.
When amino acids are rapidly degraded and ammonia levels increase within a tissue, what happens to the glutamate that has formed from transamination?
The glutamate accepts another nitrogen to form glutamine.
Glutamine then travels to the liver, kidney, or intestines where glutaminase removes the amide nitrogen to form glutamate plus ammonia.
In what form does nitrogen enter the urea cycle?
As NH4+ and aspartate.
NH4+ forms carbamoyl phosphate, which reacts with ornithine to form citrulline. Ornithine is the compound that both initiates and is regenerated by the cycle (like oxaloacetate in the TCA cycle!).
Aspartate reacts with citrulline, eventually donating its nitrogen for urea formation.
In the urea cycle, what happens upon the cleavage of arginine by arginase?
It releases urea and regenerates ornithine.
Where is carbamoyl phosphate synthetase I (CPSI) found and what does it do?
CPSI is found mainly in mitochondria of liver and intestine, and is the enzyme that catalyzes the first step of the urea cycle.
What reacts with ornithine to form citrulline?
Carbamoyl phosphate – Its high-energy phosphate bond provides the energy required to convert ornithine to citrulline, which is catalyzed by ornithine transcarbamoylase (OTC).
After being exchanged with a cytoplasmic ornithine by crossing the mitochondrial membrane to enter the cytosol, what is the fate of citrulline?
Citrulline reacts with aspartate, the second source of nitrogen for urea synthesis, to produce argininosuccinate.
How is asparate produced in the urea cycle?
Through transamination of oxaloacetate.
Upon cleavage by argininosuccinate lyase, what does argininosuccinate form?
**Fumarate **and arginine.
After being produced from the carbons of argininosuccinate provided by aspartate, what is the fate of fumarate in the urea cycle?
It is converted to malate using cytoplasmic fumarase, which is used either for the synthesis of glucose by the gluconeogenic pathway or for the regeneration of oxaloacetate by cytoplasmic reactions similar to those in the TCA cycle.
The oxaloacetate that is formed is transaminated to generate the asparate that carries nitrogen into the urea cycle. Thus, the carbons of fumarate can be recycled to asparate.
Arginine contains nitrogens derived from NH4+ and asparate. Once cleaved by arginase, what does it produce?
**Urea **and it regenerates ornithine.
