Urea Cycle Flashcards
What is responsible for generating over half of the total body pool of free amino acids?
Skeletal muscle
What structures take up free glutamine from circulation and excrete alanine?
Gut and Kidney
Describe the glucose-alanine cycle.
Alanine is synthesized in the muscle via transamination of pyruvate
Alanine is transported to the liver via circulation
Alanine is reconverted into glucose in the liver via gluconeogenesis
Glucose is transported back to the muscle
What are the four stages of Urea biosynthesis?
1) Transamination
2) Oxidative deamination of glutamate
3) Ammonia Transport
4) Reactions of the urea cycle
What is the function of transamination reactions?
Introconvert pairs of a-amino acids and a-keto acids
What is the cofactor for transaminases and what is its role?
Pyridoxal phosphate (Vit. B6)
Serves as a carrier of amino groups during transamination
What four amino acids don’t participate in transamination?
Lysine
Threonine
Proline
Hydroxyproline
The a-amino nitrogen from all amino acids that undergo transamination can be concentrated into what amino acid and why is this important?
Glutamate
Glutamate is the only amino acid that undergoes oxidative deamination at an appreciable rate in mammalian tissues
What is the function of glutamate dehydrogenase?
Catalyzes the deamination of glutamate to a-ketoglutarate, releasing NH3
NAD+ or NADP+ Can serve as the oxidoreductant
This reaction is reversible strongly favors glutamate formation
How is glutamate dehydrogenase regulated?
Stimulated: ADP
Inhibited: ATP, GTP, and NADH
What is the function of glutamine synthase?
Formation of glutamine in the mitochondria from glutamate and free Ammonia
ATP-dependent
Plays a major role in ammonia detoxification
What is the function of glutaminase and Asparaginase?
Deamidate Glutamine and Asparagine
Liver and Renal isoforms
Renal isoforms upregulated and downregulated during metabolic acidosis and alkalosis respectively
What is the function of Carbamoyl Phosphate Synthase I?
Condensation of CO2, Ammonia, and ATP to form carbamoyl phosphate
Rate-limiting step of the urea cycle
What is the function of N-acetylglutamate?
Allosteric activator of CPS I that enhances its affinity for ATP
CPS I is only active when this is present
Why does synthesis of 1 mol of carbamoyl phosphate need 2 mol of ATP?
One ATP serves as the phosphoryl donor
One ATP serves as the driving force for amide bond formation
What is the function of Ornithine transcarbamoylase?
Catalyzes the transfer of the carbamoyl group of carbamoyl phosphate to ornithine
Forms Citrulline and orthophosphate
What is the function of Argininoscuccinate Synthase?
Links aspartate and citrulline, forming argininosucinate
ATP-dependent
What is the function of Argininosuccinate lyase?
Cleave of argininosuccinate to form arginine and fumarate
What is the function of Arginase?
Cleaves Arginine to release ornithine and urea
Inhibited by ornithine and lysine
What two reactions of the urea cycle occur in the mitochondrial matrix?
CPS I
Ornithine carbamoyl transferase
What amino acid is transported into the mitochondria for use in the urea cycle?
Ornithine
What amino acid is transported out of the mitochondria during the urea cycle?
Citrulline
How is N-acetylglutamate synthesized?
Acetyl-CoA and glutamate
Where does the nitrogen come from that is released in urea?
Ammonia and Aspartate
How do Aspartate and Fumarate link the TCA cycle and the urea cycle?
Fumarate produced by argininosuccinate lyase is a TCA cycle intermediate
Transamination of oxaloacetate produces aspartate
How do you treat urea cycle defects?
Bypassing blocked steps by providing intermediates
