section 5 part 3- the urea cycle

excess N can be excreted as

• ammonia-aquatic

• urea-terrestrial vertebrates

• uric acid- birds and terrestrial reptiles

enzymes of urea cycle

2 mitochondrial

• carbamoyl phophate synthetase

• ornithine transcarbamoylase

3 cytosolic

• argininosucinate synthetase

• argininosuccinase

• arginase

in the urea cycle, GDH provides ammonia from

glutamate

cabamoyl phosphate synthetase (CPS)

catalyzed condensation and activation NH3

• syn of carbamoyl phophate

• cleavage of 2 atp

eukaryotes have how many forms of CPS

• mitochondiral CPS I

• cytosolic CPS II

CPS I

• uses ammonia as N donor and participates in urea biosynthesis

• catalyzed irreversible rxn and rate limiting step

CPS II

uses glutamine as N donor and is involed in pyrimidine biosynthesis

irreversible rxn of CPS I

• atp activates HCO3- →form carboxyphosphate and adp (intermediate)

• displacement of Pi →formation of carbamate

• carbamate phosphorylated → form ADP and carbamoyl phosphate

ornithine transcarbamoylase

• carbamoylation of ornithine→citrulline

• aa that do not occur in proteins

argininosuccinate synthetase

• 2nd N atom of urea introduced

• condensation of citrulline’s ureido group with aspartate’s amino group

• requires atp

• forms argininosuccinate

argininosuccinase

• argininosuccinate→fumarate and arginine

• arginine immediate precursor

• fumarate converted to oxaloacetate→gluconeogenesis

arginase

• catalyzes final rxn of the urea cycle

• arginine→urea and ornithine

• ornithine returned to mitochondrion where it reenters the urea cycle

CPS I activated by

N-acetylglutamate

N-acetylglutamate is synthesized from

glutamate and acetyl-CoA by N-acetyl glutamate synthase

increased AA breakdown

[glutamate] increases→stimulated N acetylglutamate synthesis→activation of CPS I→urea production increased→excretion of excess N produced by AA breakdown

remaining enzymes of the urea cycle are controlled by

concentrations of their substrates

in individuals with deficiencies in urea cycle enzyems other than arg

corresponding substrate builds up

→increase rate of dieficient rxn

→urea production is normal

total lack of a urea enzyme

LETHAL

• hyperammonemia→substrate concentrations become elevated all the way back up the cycle to ammonia

brain is particularly sensitive to

high ammonia concentrations