Carbamoyl phosphate synthase II

{{Short description|Enzyme}}

{{Infobox enzyme

| Name = Carbamoyl-phosphate synthetase (glutamine-hydrolysing)

| EC_number = 6.3.5.5

| CAS_number = 37233-48-0

| GO_code =

| image =

| width =

| caption =

}}

{{protein

|Name=carbamoyl-phosphate synthetase 1, aspartate transcarbamylase, and dihydroorotase

|caption=

|image=

|width=

|HGNCid=1424

|Symbol=CAD

|AltSymbols=

|EntrezGene=790

|OMIM=114010

|RefSeq=NM_004341

|UniProt=P27708

|PDB=

|ECnumber=

|Chromosome=2

|Arm=p

|Band=21

|LocusSupplementaryData=

}}

Carbamoyl phosphate synthetase (glutamine-hydrolysing) ({{EnzExplorer|6.3.5.5}}) is an enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol (as opposed to type I, which functions in the mitochondria). Its systemic name is hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating).{{cite journal | vauthors = Anderson PM, Meister A | title = Evidence for an activated form of carbon dioxide in the reaction catalyzed by Escherichia coli carbamyl phosphate synthetase | journal = Biochemistry | volume = 4 | issue = 12 | pages = 2803–9 | date = December 1965 | pmid = 5326356 | doi = 10.1021/bi00888a034 }}{{cite journal | vauthors = Kalman SM, Duffield PH, Brzozowski T | title = Purification and properties of a bacterial carbamyl phosphate synthetase | journal = The Journal of Biological Chemistry | volume = 241 | issue = 8 | pages = 1871–7 | date = April 1966 | doi = 10.1016/S0021-9258(18)96716-5 | pmid = 5329589 | doi-access = free }}{{cite journal | vauthors = Yip MC, Knox WE | title = Glutamine-dependent carbamyl phosphate synthetase. Properties and distribution in normal and neoplastic rat tissues | journal = The Journal of Biological Chemistry | volume = 245 | issue = 9 | pages = 2199–204 | date = May 1970 | doi = 10.1016/S0021-9258(18)63139-4 | pmid = 5442268 | doi-access = free }}{{cite journal | vauthors = Stapleton MA, Javid-Majd F, Harmon MF, Hanks BA, Grahmann JL, Mullins LS, Raushel FM | title = Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase | journal = Biochemistry | volume = 35 | issue = 45 | pages = 14352–61 | date = November 1996 | pmid = 8916922 | doi = 10.1021/bi961183y }}{{cite journal | vauthors = Holden HM, Thoden JB, Raushel FM | title = Carbamoyl phosphate synthetase: a tunnel runs through it | journal = Current Opinion in Structural Biology | volume = 8 | issue = 6 | pages = 679–85 | date = December 1998 | pmid = 9914247 | doi = 10.1016/s0959-440x(98)80086-9 }}{{cite journal | vauthors = Raushel FM, Thoden JB, Reinhart GD, Holden HM | title = Carbamoyl phosphate synthetase: a crooked path from substrates to products | journal = Current Opinion in Chemical Biology | volume = 2 | issue = 5 | pages = 624–32 | date = October 1998 | pmid = 9818189 | doi = 10.1016/s1367-5931(98)80094-x }}{{cite journal | vauthors = Raushel FM, Thoden JB, Holden HM | title = The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia | journal = Biochemistry | volume = 38 | issue = 25 | pages = 7891–9 | date = June 1999 | pmid = 10387030 | doi = 10.1021/bi990871p }}{{cite journal | vauthors = Thoden JB, Huang X, Raushel FM, Holden HM | title = Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia | journal = The Journal of Biological Chemistry | volume = 277 | issue = 42 | pages = 39722–7 | date = October 2002 | pmid = 12130656 | doi = 10.1074/jbc.M206915200 | doi-access = free }}

In pyrimidine biosynthesis, it serves as the rate-limiting enzyme and catalyzes the following reaction:

: 2 ATP + L-glutamine + HCO₃⁻ + H₂O $\backslash rightleftharpoons$ 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction)

: (1a) L-glutamine + H₂O $\backslash rightleftharpoons$ L-glutamate + NH₃

: (1b) 2 ATP + HCO₃⁻ + NH₃ $\backslash rightleftharpoons$ 2 ADP + phosphate + carbamoyl phosphate

It is activated by ATP and PRPP{{cite web|url=https://www.inkling.com/read/illustrated-reviews-biochemistry-harvey-5th/chapter-22/pyrimidine-synthesis-and|title=Unsupported Browser|last=Inkling|website=Inkling|access-date=25 April 2018}} and it is inhibited by UTP (Uridine triphosphate)Engelking LR. Pyrimidine biosynthesis. Textbook of Veterinary Physiological Chemistry. 2015;:83–7.

https://doi.org/10.1016/B978-0-12-391909-0.50014-1 Retrieved 1 April 2023

Neither CPSI nor CPSII require biotin as a coenzyme, as seen with most carboxylation reactions.

It is one of the four functional enzymatic domains coded by the CAD gene.{{cite journal|vauthors=Moreno-Morcillo M, Grande-García A, Ruiz-Ramos A, del Caño-Ochoa F, Boskovic J, Ramón-Maiques S|title=Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis|journal=Structure|volume=25|issue=6|pages=912-923|year=2017|doi=10.1016/j.str.2017.04.012|pmid=28591622|doi-access=free|hdl=10261/166586|hdl-access=free}} The CAD gene is a large gene. It uses a single strand to code for these enzyme jobs. It is classified under {{EC number|6.3.5.5}}.