BIOC/DENT/PHCY 230
LECTURE 5
glu
UREA
 synthesised mainly in liver
 maintains N in a soluble, non-toxic form
 transported in blood to kidney for excretion
 allows for the elimination of 2 nitrogens
O
H2N
C
NH2
How does nitrogen enter the urea cycle?
O
H2N
C
O
P
carbamoyl phosphate
aspartate
Carbamoyl phosphate
 synthesised from carbon dioxide and ammonia
 ammonia comes from deamination of
glutamine and glutamate
 energy requiring reaction
 catalysed by carbamoyl phosphate synthetase
(CPS)
CO2 + NH3 + 2ATP
carbamoyl- P + 2ADP + Pi
Aspartate
 aspartate is generated by transamination
glutamate + oxaloacetate
a-KG + aspartate
Entry of substrates into the urea cycle
CAC
Urea cycle
1= CPS
2= ornithine
transcarbamoylase
5= arginase
Recycling fumarate in the CAC
CAC
Overall equation for urea cycle
CO2 + NH3 + 3ATP + 2H2O
urea + 2ADP + 2Pi +AMP + PPi + fumarate
 urea synthesis is an energy demanding
process
 the equivalent of 4 ATP are consumed for
each molecule of urea synthesised
Regulation of urea cycle
Two major points of regulation:
 concentration of urea cycle enzymes
 CPS activity
CPS activity
 CPS is allosterically regulated
 N-acetylglutamate activates CPS
N-acetylglutamate synthase is activated
by arginine
positive feedback
Disorders of urea cycle enzymes:
1=CPS
2= ornithine
transcarbamoylase
Nitrogen compounds in urine
Urea - major nitrogen excretion product.
NH4+ - produced in the kidney by deamination of
glutamine. Reduces body acidity because the
process removes protons.
Uric Acid - the final metabolic product of purinenucleotide degradation.
Creatinine - derived in skeletal muscles, by
spontaneous cyclisation of creatine &
phosphocreatine.
Fates of amino acid carbon skeletons
Carbon skeletons can be glucogenic or ketogenic
Biosynthesis of amino acids
The take home message
 urea is a small organic metabolite used to eliminate
excess nitrogen from the body
 the urea cycle requires a substantial input of energy
 CPS is the key regulatory step of the urea cycle
 other N compounds are excreted in the urine
 carbon skeletons can be recycled or oxidised
 availability of carbon skeletons determines dietary
requirements for amino acids