1. UREA CYCLE

2. OUTLINE INTRODUCTION UREA CYCLE REACTION(I-V) SUMMARY REGULATION
LINK WITH TCA CYCLE
REFERENCES

3. Introduction:UREA CYCLE
Introduction:UREA CYCLE  2 NH3 + CO2 + 3 ATP + 3H2O→ urea + 2 ADP + 4 Pi + AMP
Overall equation:
First metabolic cycle elucidated.(1932).
Also known as (Krebs-Henseleit cycle)/( ornithine cycle).
It is a cycle of biochemical reactions that occurs in ureotelic organisms where the highly toxic ammonia NH3 to urea (NH2)2CO for excretion.
It’s a 5 step process each with it’s driving enzyme(bolded).
It occurs primarily in liver and in a small extent the kidneys.
It spans two liver cellular compartment the mitochondria & cytosol compartments.

4. I. Synthesis of Carbamoyl phosphate
Description
NH3(deamination)&CO2
(respiration) condense to
Carbamoyl phosphate under
Carbamoyl phosphate 1(CPS1)
in mitochondria with
NAG (N-acetylglutamate)activator.
It is the rate limiting step.
NB. NAG functions to increase the affinity that CPS1 has for ATP.
Reaction steps

5. II. Formation of Citrulline
Description
Condensation of
Carbamoyl phosphate
and Ornithine
to Citrulline by
Ornithine
transcarbamoylase.
Citrulline is then
taken to the cytosol
via a transport
system.
NB. Both ornithine and citrulline enter and exit the mitochondria respectively through their respective transporter systems on the mitochondrial membrane.

6. III. Synthesis of Arginosuccinate
Description
Condensation of Aspartate
and Citrulline by
Arginosuccinate synthase.
It utilizes one ATP which
hydrolyzes to AMP and Pyrophosphate(Ppi)
Reaction steps
NB. Reaction occurs between the amino group of the aspartate and the carbonyl group of the citrulline

7. IV. Cleavage of Arginosuccinate
Description.
Arginosuccinate is cleaved by Arginosuccinase to give Fumarate and Arginine.
The Fumarate then links with the TCA cycle while Arginine proceeds as the immediate precursor of urea.

8. V. Urea formation Description
Arginine is cleaved by Arginase to form Urea and Ornithine.
The later is taken up in the mitochondria to resume the cycle.
To mitochondrion

9. SUMMARY
NB. Zinc, Biotin and Manganese are all cofactors to their respective enzymes which they are associated with in the urea cycle.

10. Urea cycle regulation Urea cycle has a two level regulation
Level of enzyme synthesis.
Where substrate concentration determines the rate of enzyme synthesis.
Allosteric regulation
Which is determined by the rate of synthesis of
N-acetylglutamate an allosteric activator to Carbamoyl phosphate synthetase I,

11. Linking with the TCA cycle

12. REFERENCES
Principles of biochemistry --- Lehninger 6th edition (Pg ).pdf
Biochemistry ( PDFDrive ) 4thedition (Pg ).pdf
Harper’s Illustrated Biochemistry ( PDFDrive ) 31stedition (Pg 679).pdf