Nitrogen Metabolism Flashcards
Why is nitrogen catabolized into urea?
Urea is a nontoxic carrier of nitrogen atoms for excretion.
Where does urea synthesis occur?
the liver
How does nitrogen get from tissues to the liver?
Alanine and glutamine carry AA nitrogen
What are the key enzymes involved in nitrogen disposal?
Transaminases
Glutamate Dehydrogenase
Glutaminase
Urea has two nitrogens on it, where do they come from?
one N from ammonia/carbamoyl-P (from inside mitochondria)
one N from aspartate (from the cytosol)
5 Steps of urea cycle: ready go!
1) Bicarb + NH4 to Carbamoyl phosphate. Uses 2 APT and carbamoyl phosphate sythetase I (CPS1)
2) Ornithine + Carbamoyl phosphate to Citrulline. Uses ornithine transcarbamoylase
3) Citrulline + Aspartate to Argininosuccinate. Uses ATP and Argininosuccinate synthestase.
4) Argininosuccinate to Arinine + Fumarate. Uses argininosuccinate lyase.
5) Arginine to Urea + Ornithine. Uses arginase.
What is hyperammonemia?
Disorders of the urea cycle lead to condition that is toxic to nervous system health and development.
Pyridoxamine deficiency
(environmental) Lack of vitamin B6 affects many systems, such as heme synthesis, glycogen phosphorylase activity, and neurotransmitter synthesis.
Leading to dementia, dermatitis, anemia, weakness, and convulsions.
Hepatic encephalopathy
(environmental) Liver failure leading to brain dysfuction due to the liver’s inability to rid the body of toxins, including ammonia
Ammonia toxicity
(Environmental and genetic) Ammonia accumulation interferes with energy production and neurotransmitter synthesis in the brain, altering function.
Also causes brain swelling due to osmotic imbalance.
High levels of glutamine (ammonia is converted) alter mitochondrial membrane transition pores –> cell death.
Ornithine transcarbamoylase deficiency
(genetic) Most common urea-cycle defect, leading to elevated blood ammonia and orotic acid levels. Mental impairment if not treated.
Treat with compounds that aid in nitrogen removal.
How can deficiencies in other enzymes in urea cycle be distinguished?
Look for the type of intermediate that accumulate in the blood.
Argininosuccinate lyase deficiency
Treat with a massive arginine supplement. The argininosuccinate will be excreted in the urine (getting rid of the waste nitrogen).
Arginine will replenish the ornithine supply, so that the earlier steps of the cycle can continue.
What is pyridoxal phosphate (transanimation) required for?
Glycogenolysis:
glycogen phosphorylase needs this to break the alpha-1,4-linkages in glycogen.
What is the major regulatory step of the urea cycle controlled by?
CSP1 - Carbamoyl phosphate synthetase 1: converting bicarb and ammonia to activated Carbamoyl phosphate.
…and this is regulated by allosteric activation of N-acetylglutamante (NAG)
