Target intelligence / Profile preview

Cytidine triphosphate synthase (CTPS)

Target
CTPS
Molecular classification
Enzyme, Pyrimidine biosynthetic enzyme
01

Overview

Cytidine triphosphate synthase is a key enzyme (EC 6.3.4.2) in the de novo synthesis of pyrimidine nucleotides. It catalyzes the ATP- and glutamine-dependent amination of uridine triphosphate (UTP) to form cytidine triphosphate (CTP), which is essential for DNA, RNA, and phospholipid synthesis. CTPS is the rate-limiting step in cytosine nucleotide biosynthesis and is regulated by feedback from its product. The enzyme can polymerize into filaments ("cytoophidia") in cells, with regulatory implications. Increased CTPS activity has been observed in various cancers, and mutations confer drug resistance in some cell models. CTPS is a validated but challenging therapeutic target due to its central metabolic role and toxicity risks if inhibited in proliferating normal tissues.

Other names
CTP synthaseCTP synthetaseCTPSCTP enzymeEC 6.3.4.2
02

Mechanism of action

Competitive inhibition of CTP synthase activity; Depletion of cytidine triphosphate pool, inhibiting DNA/RNA synthesis; Disruption of nucleotide balance, blocking cell proliferation

03

Biological functions

Pyrimidine nucleotide biosynthesisCell proliferationRegulation of nucleotide poolsRegulation of cell growth and divisionPhospholipid biosynthesisHomeostasis of nucleic acid synthesis
04

Disease associations

Cancerelevated CTPS activity in tumorsresistance to cytotoxic drugs like cytosine arabinoside in cell models
05

Safety considerations

Potential cytotoxicity due to nucleotide depletion in normal cellsRisk of hematologic toxicity when used in cancer therapy (inferred from mechanism; not frequently used clinically)
06

Interacting drugs

Cytosine arabinoside (ara-C)

1 more in the full profile.

07

Biomarkers

CTPS expression/activity has been investigated as a biomarker for cell proliferation and tumorigenesis

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