Evidence map›Paper›PMID 39952693›Full record

ReviewPharmacological reviews2025

Biochemistry, pharmacology, and in vivo function of arginases.

Sophia K Heuser, Junjie Li, Silke Pudewell, Anthea LoBue, Zhixin Li, Miriam M Cortese-Krott

Abstract readReview
In one paragraph

Review in Pharmacological reviews, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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  5. Article
  6. Leveraging Macrophage Metabolic Reprogramming for Enhanced Anti-Tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Frontiers in cellular and infection microbiology · 2026
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Sophia K HeuserMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Junjie LiMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Silke PudewellDepartment of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Anthea LoBueMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Zhixin LiMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Miriam M Cortese-KrottMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Cardiovascular Research Institute Düsseldorf, Düsseldorf, Germany; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Electronic address: miriam.cortese@hhu.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The enzyme arginase catalyzes the hydrolysis of l-arginine into l-ornithine and urea. The 2 existing isoforms Arg1 and Arg2 exhibit different cellular localizations and metabolic functions. Arginase activity is crucial for nitrogen detoxification in the urea cycle, synthesis of polyamines, and control of l-arginine bioavailability and nitric oxide (NO) production. Despite significant progress in the understanding of the biochemistry and function of arginases, several open questions remain. Recent studies have revealed that the regulation and function of Arg1 and Arg2 are cell type-specific, species-specific, and profoundly different in mice and humans. The main differences are in the distribution and function of Arg1 and Arg2 in immune and erythroid cells. Contrary to what was previously thought, Arg1 activity appears to be only partially related to vascular NO signaling under homeostatic conditions in the vascular wall, but its expression is increased under disease conditions and may be targeted by treatment with arginase inhibitors. Arg2 appears to be mainly a catabolic enzyme involved in the synthesis of l-ornithine, polyamine, and l-proline but may play a putative role in blood pressure control, at least in mice. The immunosuppressive role of arginase-mediated arginine depletion is a promising target for cancer treatment. This review critically revises and discusses the biochemistry, pharmacology, and in vivo function of arginases, focusing on the insights gained from the analysis of cell-specific Arg1 and Arg2 knockout mice and human studies using arginase inhibitors or pegylated recombinant arginase. SIGNIFICANCE STATEMENT: Further basic and translational research is needed to deepen our understanding of the regulation of Arg1 and Arg2 in different cell types in consideration of their localization, species-specificity, and multiple biochemical and physiological roles. This will lead to better pharmacological strategies to target arginase activity in liver, cardiovascular, hematological, immune/infectious diseases, and cancer.

Indexed as

ArginaseAnimalsArginineHumansNeoplasmsNitric OxideArginaseArginineNitric Oxideanimal modelscancercardiovascular diseaseimmunopharmacologyL-arginineliver diseasenitric oxide synthase

Identifiers

PMID39952693
PMCPMC12105760

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.