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Unit 3 Urea cycle.pptx
1. UREA CYCLE
The urea cycle consists of five reactions:
Two mitochondrial and three cytosolic.
•The cycle converts two amino groups:
•One Nitrogen of Urea is supplied by ammonia
•Second Nitrogen of Urea is supplied by Aspartate
•A carbon atom from CO2 to the relatively nontoxic
excretion product urea.
* Requires four "high-energy" phosphate bonds.
2. Overall reaction of the urea cycle
Aspartate+ NH3 + CO2 + 3 ATP
Urea + fumarate+2ADP +AMP + 2 Pi + Ppi+
3H2O
4. Step 1 : Reaction is catalyzed
by carbamoyl phosphate
synthetase which converts
NH3 and CO2 to carbamoyl
phosphate, utilizing ATP.
Step 2: catalysed by
ornithine
transcarbamoylase which
transfers a carbamoyl group
from carbamoyl phosphate
to ornithine to form
citrulline.
5. Step 3: reaction is catalyzed by
argininosuccinate synthetase.
This enzyme uses ATP to activate
citrulline by forming a citrullyl-
AMP intermediate.
This intermediate is attacked by
the amino group of an aspartate
residue to form
argininosuccinate.
6. Step 4: This step is catalyzed
by argininosuccinate lyase
which cleaves
argininosuccinate into
fumarate and arginine.
Step 5: The last step is
catalyzed by arginase which
cleaves arginine to produce
urea and ornithine completing
the cycle.
8. The urea is transported to the kidney, where it is
filtered from the blood and finally sent to the
bladder for excretion in the urine.
Nitrogen is also lost through hair, skin, GI cells
mucus, nails, and body fluids like sweat
10. Urea cycle and the tricarboxylic acid cycle are coupled
together through fumarate and aspartate.
Thus unless the fumarate released when arginosuccinate
is cleaved can be cycled through the TCA cycle to
oxaloacetate, the urea cycle will be slowed or inhibited.
11. Fumarate is the precursor to oxaloacetate
Oxaloacetate can:
-- be transaminated to aspartate and feed back into urea
cycle
-- condense with AcCoA and feed into citric acid cycle
-- proceed into gluconeogenesis
-- be converted to pyruvate