Amino Acid Catabolism and Urea Cycle Disorders Flashcards
glutamate dehydrogenase
converts glutamate to a-KG or vice versa depending on substrate levels.
also allosterically regulated by energy levels- ATP, GTP inhibit whereas ADP and GDP activate
what is the equation for urea synthesis?
CO2 + NH4 + ATP + Aspartate + H2O = urea +ADP, + Pi + AMP + PPi + fumarate
describe the urea cycle
inside the mitochondria, CO2 + NH3 + 2 ATP are converted to carbanoyl phosphate by carbonyl phosphate synthetase 1
ornthinine trans-carbamoylase converts carbonyl phosphate to L-citrulline
Citrulline is transported into the cytosol
argininosuccinate synthase combines citrulline and aspartate to form argininosuccinate
argininosuccinate is converted to L-arginine via argininosuccinate lyase, giving off a fumarate in the process. that fumarate will regenerate the aspartate used previously
arginine is converted to ornthinine and urea via arginase, and the ornthinine is transported back into the mitochondria
describe the regulation of the urea cycle
rate limiting step is carbamoyl phosphate synthetase 1, which is allosterically activated by N-acetyl glutamate, which is tied to AA levels
how are amino groups transported to the liver for the urea cycle
- glutamine synthase- glutamate + NH4 + ATP = glutamine + ADP
in the liver, glutaminase-
glutamine + H20 = glutamate + NH4
- glucose-alanine cycle, where muscle transaminates pyruvate into alanine, which is then transported to the liver
what are the defining features of a urea cycle disorder?
hyperammonemia, encephalopathy, respiratory alkalosis, neurotoxic effects
OTC
late onset urea acid cycle disease that is X-linked and is the most common late onset urea acid cycle disease
how do you treat urea acid cycle disease?
limit dietary protein and activate alternative pathways for nitrogen disposal
ex. sodium phenylbutyrate
