Carbamoyl phosphate explained

Carbamoyl phosphate is an anion of biochemical significance. In land-dwelling animals, it is an intermediary metabolite in nitrogen disposal through the urea cycle and the synthesis of pyrimidines. Its enzymatic counterpart, carbamoyl phosphate synthetase I (CPS I), interacts with a class of molecules called sirtuins, NAD dependent protein deacetylases, and ATP to form carbamoyl phosphate. CP then enters the urea cycle in which it reacts with ornithine (a process catalyzed by the enzyme ornithine transcarbamylase) to form citrulline.

Classification

Carbamoyl phosphate is a metabolic intermediate in a pathway that involves nitrogen disposal through the urea cycle and the biosynthesis of pyrimidines.^[1]

Production

It is produced from bicarbonate, ammonia (derived from amino acids), and phosphate (from ATP).^[2] The synthesis is catalyzed by the enzyme carbamoyl phosphate synthetase. This uses three reactions as follows:

• + ATP → ADP + (carboxyl phosphate)
• + NH₃ + OH⁻ → + ⁻O–C(O)NH₂ + H₂O
• ⁻O–C(O)NH₂ + ATP → ADP +

Clinical significance

A defect in the CPS I enzyme, and a subsequent deficiency in the production of carbamoyl phosphate has been linked to hyperammonemia in humans.^[3]

See also

• Ornithine transcarbamylase
• Citrulline
• Urea Cycle

References

Further reading

• Book: Nelson DL, Cox MM . Lehninger Principles of Biochemistry fourth edition . W. H. Freeman and company . New York . 978-0-7167-4339-2 . 2005 . registration .

Notes and References

1. Book: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A, Ah Mew N, Simpson KL, Gropman AL, Lanpher BC, Chapman KA, Summar ML . Urea Cycle Disorders Overview . Adam MP, Feldman J, Mirzaa GM, etal . Gene Reviews . University of Washington, Seattle . 1993 . 20301396.
2. Book: Bhagavan NV, Ha CE . Protein and Amino Acid Metabolism . 2015 . Essentials of Medical Biochemistry . Second . 227–268. Bhagavan NV, Ha CE. San Diego. Academic Press. en. 10.1016/b978-0-12-416687-5.00015-4. 978-0-12-416687-5 .
3. Nakagawa T, Lomb DJ, Haigis MC, Guarente L . SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle . Cell . 137 . 3 . 560–570 . May 2009 . 19410549 . 2698666 . 10.1016/j.cell.2009.02.026 . vanc .