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rate-limiting unreviewed

Carbamoyl phosphate synthetase I (CPS I)

1 reactions · 1 pathways

Cofactors used

ATP Bicarbonate/CO2 Pi

Clinical / pharmacological. CPS I deficiency: hyperammonaemia, normal orotic acid

What it does, reaction by reaction

1 reactions

Urea Cycle Amino Acid & Nitrogen Metabolism · Mitochondrial matrix + cytosol

step 1 Irreversible rate-limiting

NH₄⁺ + HCO₃⁻ + 2 ATP → carbamoyl phosphate + 2 ADP + Pᵢ

Converts NH4+ HCO3- ATP into Carbamoyl phosphate ADP Pi

› Notes

In the mitochondrial matrix, carbamoyl phosphate synthetase I (CPS I) uses MgATP and requires N-acetylglutamate (NAG) as an obligatory allosteric activator. This is the rate-limiting, committed, and essentially irreversible step of the urea cycle; it consumes two high-energy phosphate bonds.

Showing all 1 reactions.

What accelerates and inhibits it

Regulation is pathway-specific, so each context is listed separately

1 entries

Urea Cycle

Accelerated by

N-acetylglutamate (obligatory); increased mitochondrial ammonia

Inhibited by

Absence of N-acetylglutamate; no principal direct physiologic inhibitor

Hormonal control

Glucagon and cortisol increase expression during fasting/high-protein catabolism; insulin lowers net ureagenic demand in the fed state

Recent literature

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Europe PMC · fetched just now · sorted by publication date

  1. 1
    Neurotransmitter receptor-associated gene signature: prognostic and immunosuppressive microenvironment in NSCLC.

    Yang Y, Ge A, Xu Y, Li J, Shi W, Wang J, Zhao Z. · 2026-01-06

    open access unreviewed
  2. 2
    Growth-mode-independent glutamine/glutamate/aspartate metabolic shift and urea cycle remodeling driven by FOXA1 in benzo[a]pyrene-transformed human bronchial epithelial cells.

    Fu Y, Qi Y, Xing Y, Lin Y, Liu Z, Fu J, Yao B, Zhao P. · 2026-06-16

    unreviewed
  3. 3
    Mechanism of Jianpi Qinghua granule in ameliorating metabolic dysfunction-associated fatty liver disease by targeting the DNMT-urea cycle axis.

    Xiao Y, Wu H, Ju W, Xu J, Chen C, Abuduhelili B, Cai M, Jin S, Yin Q, Tian J, Lu H, Han X. · 2026-05-08

    unreviewed
  4. 4
    In Vivo Base Editing for Neonatal Inborn Errors of Metabolism: Clinical Progress, N-of-1 Therapy, and the Ethics of Bespoke Genetic Medicine.

    Li OM, Li Y, Li SXT. · 2026-08-11

    unreviewed
  5. 5
    Integrated mesenchymal and extracellular cues drive bioengineered liver tissue formation and function.

    Ye S, Wang Z, Dirk Delemarre M, Liv N, van den Dikkenberg A, Vermonden T, van der Laan L, Malda J, Spee B, G … · 2026-06-09

    open access unreviewed
  6. 6
    Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).

    Zhu B, Wang C, Liu P, Qu Z, Qi R, Chen S, Niu H. · 2026-06-11

    open access unreviewed
  7. 7
    Metabolic checkpoint CPS1 sustains TCA anaplerosis via urea cycle in IDH-mutant gliomas.

    Xu H, Zhang L, Fu M, Yang H, Wu R, Ma J, You M, Zhang J, Lv K, Wu Y, Ye D, Hua W. · 2026-05-21

    unreviewed
  8. 8
    Three-dimensional organoid culture enhances functional maturation of human pluripotent stem cell-derived hepatocytes.

    Ghanem SS, Al-Barazenji T, Badi R, Abdelalim EM. · 2026-07-29

    unreviewed
  9. 9
    A deep intronic CPS1 variant causing pseudo-exon activation identified in an adult with molecularly unconfirmed urea cycle disorder.

    Honto M, Imagawa E, Mochizuki H, Sako S, Nishida H, Tsunogai T, Oishi K. · 2026-07-19

    unreviewed
  10. 10
    A phase-variable capsule facilitates <i>Akkermansia muciniphila</i> colonization of the intestinal mucus layer.

    Gracia L, Hughes ER, Middleton DR, Mueller KD, Portillo JA, Sharma A, Davey L, Panzetta ME, Chanin RB, Bhatt … · 2026-06-18

    unreviewed

External claims. These come from an index outside this database and are not checked against it. Treat them as leads.