3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

Microbe Notes
Online Microbiology and Biology Study Notes

Menu

Search … Search

Home » Biochemistry » Urea Cycle- Enzymes and Steps

Urea Cycle- Enzymes and Steps

August 11, 2018 by Sagar Aryal

Biology Educational Videos

Table of Contents [ hide ]

Location of Urea Cycle
Steps in the Urea Cycle
Important enzymes in Urea Cycle
Regulation of Urea Cycle
Purpose of the Urea Cycle
Related Diseases of Urea Cycle
References

Last Updated on February 4, 2021 by Sagar Aryal

The urea cycle is the metabolic pathway that transforms nitrogen to urea for
excretion from the body.
Nitrogenous excretory products are removed from the body mainly in the urine.
Ammonia, which is very toxic in humans, is converted to urea, which is
nontoxic, very soluble, and readily excreted by the kidneys.
The urea excreted each day by a healthy adult (about 30 g) accounts for about
90% of the nitrogenous excretory products.

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 1/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

Urea is formed in the urea cycle from NH4+, CO2, and the nitrogen of
aspartate.
The cycle occurs mainly in the liver.

Location of Urea Cycle

Cytosol and mitochondria of hepatocytes.

Substrates: NH3 (as derived from oxidative deamination of glutamate); CO2;

aspartate; three ATP.
Products: Urea; fumarate; H2O.

Steps in the Urea Cycle

1. Transport of nitrogen to the liver

Ammonia is very toxic, particularly to the central nervous system.

The concentration of ammonia and ammonium ions in the blood is normally
very low.

(NH3 + H+ ↔ NH4+)

Ammonia travels to the liver from other tissues, mainly in the form of alanine
and glutamine.

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 2/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

It is released from amino acids in the liver by a series of transamination and

deamination reactions.
Ammonia is also produced by bacteria in the gut and travels to the liver via the
hepatic portal vein.

2. Reactions of the urea cycle

NH4+ and aspartate provide the nitrogen that is used to produce urea, and CO2
provides the carbon. Ornithine serves as a carrier that is regenerated by the cycle.

Carbamoyl phosphate is synthesized in the first reaction from NH4+, CO2, and
two ATP. Inorganic phosphate and two ADP are also produced.
Enzyme: carbamoyl phosphate synthetase I, which is located in mitochondria
and is activated by N-acetylglutamate.
Ornithine reacts with carbamoyl phosphate to form citrulline. Inorganic
phosphate is released.
Enzyme: ornithine transcarbamoylase, which is found in mitochondria. The
product, citrulline, is transported to the cytosol in exchange for cytoplasmic
ornithine.
Citrulline combines with aspartate to form argininosuccinate in a reaction that
is driven by the hydrolysis of ATP to AMP and inorganic pyrophosphate.
Enzyme: Argininosuccinate synthetase
Argininosuccinate is cleaved to form arginine and fumarate.
Enzyme: argininosuccinate lyase. This reaction occurs in the cytosol.
The carbons of fumarate, which are derived from the aspartate added in
reaction 3, can be converted to malate.
In the fasting state in the liver, malate can be converted to glucose or to
oxaloacetate, which is transaminated to regenerate the aspartate required for
reaction 3.
Arginine is cleaved to form urea and regenerate ornithine.
Enzyme: arginase, which is located primarily in the liver and is inhibited by
ornithine.
Urea passes into the blood and is excreted by the kidneys.
Ornithine is transported back into the mitochondrion (in exchange for citrulline)
where it can be used for another round of the cycle.
When the cell requires additional ornithine, it is synthesized from glucose via
glutamate.

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 3/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

Arginine is a nonessential amino acid in adults. It is synthesized from glucose

via ornithine and the first four reactions of the urea cycle.

Important enzymes in Urea Cycle

Carbamoyl phosphate synthetase I: Converts ammonium and bicarbonate
into carbamoyl phosphate. This is the rate-limiting step in the urea cycle. This
reaction requires two ATP and occurs in the mitochondria.
Ornithine transcarbamoylase: Combines ornithine and carbamoyl phosphate
to form citrulline. Located in mitochondria.
Argininosuccinate synthetase: Condenses citrulline with aspartate to form
arginosuccinate. This reaction occurs in the cytosol and requires one ATP.
Argininosuccinate lyase: Splits argininosuccinate into arginine and fumarate.
Occurs in the cytosol.
Arginase: Cleaves arginine into one molecule of urea and ornithine in the
cytosol. The ornithine is then transported back into the mitochondria for entry
back into the cycle.

Regulation of Urea Cycle

Carbamoyl phosphate synthetase I catalyzes the rate-limiting step of the cycle
and is stimulated by N -acetylglutamate.
Although the liver normally has a great capacity for urea synthesis, the
enzymes of the urea cycle are induced if a high-protein diet is consumed for 4
days or more.

Purpose of the Urea Cycle

The urea cycle allows for the excretion of NH4+ by transforming ammonia into urea,
which is then excreted by the kidneys.

Related Diseases of Urea Cycle

Hyperammonemia occurs when there is a deficiency in one of more of the urea
cycle enzymes, causing insufficient removal of NH4+.
Ammonia intoxication leads to CNS deterioration in the form of mental
retardation, seizure, coma, and death.

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 4/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

References
1. Smith, C. M., Marks, A. D., Lieberman, M. A., Marks, D. B., & Marks, D. B.
(2005). Marks’ basic medical biochemistry: A clinical approach. Philadelphia:
Lippincott Williams & Wilkins.
2. Lehninger, A. L., Nelson, D. L., & Cox, M. M. (2000). Lehninger principles of
biochemistry. New York: Worth Publishers.
3. John W. Pelley, Edward F. Goljan (2011). Biochemistry. Third edition.
Philadelphia: USA.
4. Madigan, M. T., Martinko, J. M., Bender, K. S., Buckley, D. H., & Stahl, D. A.
(2015). Brock biology of microorganisms (Fourteenth edition.). Boston:
Pearson.
5. Rodwell, V. W., Botham, K. M., Kennelly, P. J., Weil, P. A., & Bender, D. A.
(2015). Harper’s illustrated biochemistry (30th ed.). New York, N.Y.: McGraw-
Hill Education LLC.

Read Also ...

Krebs cycle / Citric acid cycle / TCA Cycle with steps and diagram
TCA Cycle (Citric acid cycle or Krebs cycle)
33 Difference between enzymes and hormones (enzymes vs hormones)
Nitrogen Cycle- Steps and Significance
Translation (Protein Synthesis)- Definition, Enzymes and Steps
Prokaryotic DNA Replication- Enzymes, Steps and Significance
Carbon Cycle- Definition, Steps, Examples, Significance, Human Impacts
Phosphorus Cycle- Definition, Steps, Examples, Significance, Human Impacts
Sulfur Cycle- Definition, Steps, Examples, Significance, Human Impacts
Glycolysis- definition, equation, enzymes, 10 Steps with diagram

Biochemistry
Urea, Urea Cycle, Urea Cycle diseases, Urea Cycle enzymes, Urea Cycle location,
Urea Cycle purpose, Urea Cycle regulation, Urea Cycle Steps
Lipids- definition, properties, structure, types, examples, functions
Phenylalanine Deaminase Test

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 5/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

Leave a Comment

Name *

Email *

Save my name, email, and website in this browser for the next time I comment.

Post Comment

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Buy me a coffee :) 0

Notes Categories

Select Category

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 6/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

Subscribe for regular latest notes

Microbe Notes Android App

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 7/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

Read Also:

Krebs cycle / Citric acid cycle / TCA Cycle with steps and diagram

TCA Cycle (Citric acid cycle or Krebs cycle)

33 Difference between enzymes and hormones (enzymes vs hormones)
Nitrogen Cycle- Steps and Significance

Translation (Protein Synthesis)- Definition, Enzymes and Steps

Prokaryotic DNA Replication- Enzymes, Steps and Significance

Carbon Cycle- Definition, Steps, Examples, Significance, Human Impacts

Phosphorus Cycle- Definition, Steps, Examples, Significance, Human Impacts
Sulfur Cycle- Definition, Steps, Examples, Significance, Human Impacts

Glycolysis- definition, equation, enzymes, 10 Steps with diagram

DNA Replication- definition, enzymes, steps, mechanism, diagram

Microbial degradation of cellulose (Enzymes, Steps, Mechanisms)

Microbial degradation of hemicellulose (Enzymes, Steps, Mechanisms)
Microbial degradation of chitin (Enzymes, Steps, Mechanisms)

Microbial degradation of lignin (Enzymes, Steps, Mechanisms)

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 8/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

Microbial degradation of pectin (Enzymes, Steps, Mechanisms)

Prokaryotic Transcription- Enzymes, Steps, Significance

Cell Cycle- Definition, Phases, Regulation and Checkpoints

Enzymes- Properties, Classification and Significance

Menstrual Cycle- definition, hormones, phases, diagram

Oogenesis / Ovulation / Ovarian cycle- Definition, Phages, Process
Interphase- definition, stages, cell cycle, diagram, video

Hand washing steps and guidelines by WHO and CDC with video
Eukaryotic DNA Replication- Features, Enzymes, Process, Significance
Electron Transport Chain (ETC)- Components and Steps

Glycolysis- Steps, ATP generation and Significance

Recombinant DNA Technology- Steps, Applications and Limitations

Gluconeogenesis- Steps, Reactions and Significance

Homology Modeling- Working, Steps, and Uses
Southern Blot- Principle, Steps and Applications

All Notes (Categories wise)

Microbiology Dictionary

Short Answer Questions

Top 10 in Microbiology
Product Review

Advertise with us

Request Notes
About Us
Our Team

Contact Us

Disclaimer (Terms and Conditions)

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 9/10
3/9/2021 Urea Cycle- Enzymes and Steps | Biochemistry | Microbe Notes

Privacy Policy
Cookie Policy

© 2021 Microbe Notes. Made with ♡ by Sagar Aryal.

https://microbenotes.com/urea-cycle-enzymes-and-steps/ 10/10