UREA CYCLE

1. NETAJISUBHASCHANDRA BOSE INSTITUTE OF PHARMACY
Tatla, Roypara, Chakdaha, Dist. Nadia, PIN 741222, W.B.
Affiliated to
MAULANAABULKALAMAZAD UNIVERSITY OF TECHNOLOGY (MAKAUT)
BF 142, Sector 1, Salt Lake City, Kolkata 700064, West Bengal

2. INTRODUCTION:
Urea cycle is the first metabolic cycle to be elucidated.
The cycle is known as Krebs-HenseleitUrea cycle.
Ornithineis the first member of the reaction, it is also called as Ornithinecycle.
Urea is the major end product of protein metabolism (amino acid metabolism) in
humans and mammals.
Urea has two amino (-NH
2) groups, one derived from NH
3and the other from
aspartate.
Urea is synthesized in the liver.
Than secreted into blood stream.
And taken up by the kidneys for excretion in the urine.
Urea synthesis is a five step cyclic process, with five distinct enzymes.
The first two enzymes are present in mitochondria while the rest are localized in
cytosol.

3. CHARACTERISTICS:
Urea is the major disposal form of amino groups.
It accounts for 90% of the nitrogen containing components of urine.
The urea cycle is the sole source of endogenous production of arginine.
Urea formation takes place in liver.
Urea excretion occurs through kidney.

4. SYNTHESIS:
STEP I: -Formationof carbamoylphosphate
CO
2+ NH
4+ 2 ATP CarbamoylPhosphate + 2
ADP + 2Pi
CarbamoylPhosphate Synthase-I
N-Acetyl Glutamicacid
STEP II: -Formation of citrulline
Ornithine+ CarbamoylPhosphate Citrulline+ Pi
OrnithineTranscarbamoylase
STEP III: -Formation of Arginosuccinate
Citrulline+ Aspartate+ ATP
Arginosuccinatesynthase
Arginosuccinate+
AMP + PPi

5. STEP IV: -Formation of Arginine
STEP V: -Formation of Urea
Arginosuccinate Arginine+ Fumarate
Arginosuccinase
Arginine+ H
2O
Arginase
Urea + Ornithine
This Ornithineagain bind with CarbamoylPhosphate to form Citrulline. That’s why it is a cyclic
process.

6. Overall reaction and energetic:
The urea cycle is irreversible and consumes 4 ATP. Two ATP are utilized for the synthesis of
carbamoylphosphate. One ATP is converted to AMP and PPito produce arginosuccinatewhich
equals to 2 ATP. Hence 4 ATP are actually consumed.

7. Regulation of Urea Cycle: -
Carbamoylphosphate synthase(CPS-I) is rate limiting enzyme in Urea cycle.
CPS–I is allostericallyactivated by N–acetylglutamate(NAG).
It is synthesized from glutamate and acetyl CoAby synthaseand degraded by a hyrolase.
The rate of Urea synthesis in liver is correlated with the concentration of N–acetylglutamate.
Formation and degradation of N-acetylglutamate

8. Interrelation between Urea cycle and TCAcycle: -

9. Metabolic disorders of Urea cycle: -
Disorders Defective Enzymes Product accumulated
Hyperammonemia-I CarbamoylPhosphate
Synthase-I
Ammonia
Hyperammonemia-II OrnithineTranscarbamoylaseAmmonia
Citrullinemia ArginosuccinateSynthase Citrulline
Arginosuccinicaciduria Arginase Arginosuccinate
Argininemia Arginase Arginine

10. Blood Urea Significance: -
Normal blood Urea concentration is 10-40 mg/dl.
About 15-30 gm of Urea (7-15 gm nitrogen) is excreted in Urine per day.
Blood Urea estimation is a screening test for the evaluation of kidney(renal) function.
Elevation in blood Urea may be broadly classified into three categories.

11. Blood Urea Significance (continued): -
Renal:
In renal disorders like acute glomerulonephritis, chronic nephritis, nephrosclerosis, polycystic
kidey, blood Urea is increased.
Post-renal:
Due to obstruction in the Urinary tract (e.g. tumors, stones, enlargement of prostate gland
etc.) blood Urea is elevated.
This is due to increased reabsorptionof Urea from the tubules.
Pre-renal:
This is associated with increased protein breakdown, leading to a negative nitrogen balance.
Observed after major surgery, prolonged fever, diabetic coma, thyrotoxicosisetc.
In leukemia & bleeding disorders also, blood Urea is elevated.

12. REFERENCES
1.Book of Biochemistry, by U. Satyanarayana& U. Chakrapani, Third
Edition, Page no. 337-341.
2.www.slideshare.net
3.www.fppt.com