Nitrogen Waste and Urea Cycle Flashcards
What comes from the muscles during the fasting state?
Alanine
Glutamine
When is the urea cycle running?
During both the fasted and the fed state
First step in the urea cycle?
CO2 + NH4+ -> carbamoyl phosphate
What enzyme catalyzes CO2+NH4+?
Carbamoyl Phosphate Synthetase I
Where does the NH4+ come from to create carbamoyl phosphate?
Glutamate -> alpha-KG +NH4+
What does carbamoyl phosphate react with?
Ornithine
What reaction does ornithine transcarbamylase catalyze?
Ornithine + carbamoyl phosphate -> Citrulline
What does citrulline react with making what?
Aspartate making arginosuccinate
What enzyme catalyzes citrulline + aspartate?
Arginosuccinate synthetase
Where do the two ammonia come from in the urea?
Aspartate
Free ammonia that came off glutamate
Where do these reactions take place?
Liver but in the mitochondria everything up to citrulline which enters the cytosol
What does aspartate transaminase do?
Converts OAA to aspartate
What diseases show elevated AST and ALT enzymes?
Hepatitis A and B
Acetaminophen
Shock
What happens in alcoholic liver disease?
AST>ALT 2:1 ratio
Most common urea cycle deficiency?
Ornithine transcarbamylase (OTC)
How is OTC deficiency passed on?
X-linked
What occurs with OTC deficiency?
Encephalopathy as the brain is the most sensitive to accumulating ammonia
Treatment of OTC deficiency?
Low-protein diet, nitrogen scavenger supplement, essential AAs
What is the most severe urea cycle disorder?
Carbamoyl phosphate synthetase I (CPSI)
What is the mode that CPSI is passed on?
Autosomal recessive
Symptoms of CPSI disorder?
Hyperammonemia
Poorly regulated breathing
Poorly regulated temperature
Does not eat
What are the ultimate treatments for urea cycle disorders?
Functional liver transplant
