| 2022 |
Human AGMAT (annotated as agmatinase) was shown biochemically to hydrolyze linear guanidino acids (taurocyamine, guanidinobutyrate, guanidinopropionate, guanidinoacetate) but was virtually inactive with agmatine as substrate. A negatively charged group at the end opposing the guanidine moiety was essential for catalysis. Two naturally occurring variants differ in substrate preferences. The authors propose renaming AGMAT as guanidino acid hydrolase (GDAH). Additionally, AGMAT substrates taurocyamine, guanidinobutyrate, and guanidinopropionate were shown to be produced by human glycine amidinotransferase (GATM), placing AGMAT downstream of GATM in guanidino acid metabolism. |
In vitro biochemical assays, structural modelling, direct substrate profiling, mutagenesis/variant analysis |
Scientific reports |
High |
36543883
|
| 2025 |
In torpid bats, AGMAT co-localizes with carbamoyl-phosphate synthase 1 (CPS1) in liver, as demonstrated by proteomic analysis, confocal microscopy, and fluorescence resonance energy transfer (FRET), indicating a physical association (indirect interaction) between AGMAT and CPS1. This interaction was conserved across two phylogenetically distant bat species (Myotis ricketti and Rhinolophus ferrumequinum), suggesting AGMAT participates in coordinated nitrogen metabolism with the urea cycle during torpor. |
Proteomics, confocal co-localization microscopy, FRET |
bioRxivpreprint |
Medium |
bio_10.1101_2025.09.26.678923
|
| 2014 |
In vivo morpholino antisense knockdown of AGMAT (combined with ODC1 knockdown) in ovine conceptuses demonstrated that the ADC/AGMAT pathway (arginine → agmatine → putrescine) functions as a rescue/alternative polyamine biosynthesis route when the classical ODC1 pathway is compromised, supporting conceptus survival and development. |
In vivo morpholino antisense oligonucleotide knockdown, polyamine quantification, mRNA/protein analysis in ovine conceptuses |
Biology of reproduction |
High |
24648395
|
| 2017 |
In vivo knockdown of AGMAT translation (combined with ODC1 knockdown) in ovine conceptuses resulted in 78% morphologically abnormal and non-elongated conceptuses and reduced pregnancy rate (22%), establishing that AGMAT is required for adequate polyamine synthesis and conceptus development during peri-implantation pregnancy. Compensation occurred through upregulation of ADC, SLC22A1, SLC22A2, and SLC22A3 mRNAs. |
In vivo morpholino antisense oligonucleotide knockdown, polyamine quantification, mRNA expression analysis, pregnancy outcome assessment |
Amino acids |
High |
29196820
|
| 2019 |
AGMAT overexpression in lung adenocarcinoma cells promotes tumorigenesis by upregulating iNOS expression, thereby increasing nitric oxide (NO) release. Elevated NO activates MAPK and PI3K/Akt-dependent c-Myc activity, upregulating cyclin D1 and driving cell proliferation. This pathway was validated in vitro and in xenograft models using NO scavenger (Carboxy-PTIO), iNOS inhibitor (SMT), and confirmed by functional assays. |
Gain/loss-of-function cell assays, NO detection (DAF-FMDA probe, nitrite assay), pharmacological inhibitors, xenograft tumor model, western blot |
Cell death & disease |
Medium |
31699997
|
| 2022 |
AGMAT overexpression in pancreatic adenocarcinoma cells activates the TGFβ/Smad signaling pathway and enhances epithelial-mesenchymal transition (EMT), promoting cell proliferation and metastasis, as shown by gain- and loss-of-function experiments with western blot pathway analysis. |
Gain/loss-of-function experiments, CCK-8 assay, colony formation, migration/invasion assays, western blot for TGFβ/Smad pathway components |
Experimental and therapeutic medicine |
Medium |
35837051
|
| 2023 |
The oncogenic transcription factor c-Myc binds to the AGMAT promoter and transcriptionally upregulates AGMAT expression in colorectal cancer cells, as demonstrated by promoter-binding assays. AGMAT knockdown via AAV9-shRNA in a colitis-associated CRC mouse model reduced tumor number and size, decreased PCNA expression, and inhibited AKT and ERK phosphorylation, placing AGMAT upstream of PI3K/AKT and ERK signaling in CRC progression. |
Promoter-binding assay (c-Myc binding to AGMAT promoter), AAV9-shRNA knockdown in AOM/DSS mouse model, western blot for AKT/ERK phosphorylation, in vitro proliferation/apoptosis assays |
Human gene therapy |
Medium |
36680755
|
| 2023 |
AGMAT was validated as a direct target of miR-151a-5p in colorectal carcinoma by dual luciferase reporter assay, establishing that miR-151a-5p suppresses AGMAT to promote CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition. |
Dual luciferase reporter assay, gain/loss-of-function cell assays for proliferation, migration, invasion |
Oncology reports |
Medium |
36704851
|
| 2023 |
AGMAT overexpression in the ventral hippocampus of rats elicited depressive- and anxiety-like behaviors, whereas AGMAT knockdown in the same region had antidepressant and anxiolytic effects in chronic restraint stress animals. Electrophysiological recordings revealed that AGMAT blockade increased Schaffer collateral-CA1 excitatory synaptic transmission both pre- and post-synaptically, likely through inhibition of AGMAT-expressing local interneurons. |
Stereotaxic viral vector overexpression/knockdown in rat ventral hippocampus, behavioral testing, field and whole-cell electrophysiological recordings |
Neuropharmacology |
Medium |
36849038
|
| 2016 |
Agmatinase (Agmat) is upregulated in the prefrontal cortex and hippocampus of CRTC1 knockout mice, and this upregulation is localized to parvalbumin- and somatostatin-positive interneurons, as confirmed by confocal immunofluorescence microscopy and qPCR/western blot. Acute agmatine treatment rescued the depressive-like behavior of Crtc1−/− mice, consistent with agmatine deficit due to elevated AGMAT-mediated degradation. Agmatine also decreased eEF2 phosphorylation in the PFC, suggesting NMDA receptor antagonist-like mechanism. |
Microarray gene expression profiling, qPCR, western blot, confocal immunofluorescence microscopy, behavioral testing (forced swim test), pharmacological agmatine/ketamine treatment |
Translational psychiatry |
Medium |
27404284
|
| 2025 |
Exosomal miR-33a secreted by cancer cells targets AGMAT in cancer-associated fibroblasts (CAFs), suppressing putrescine biosynthesis. Reduced putrescine in CAFs inhibits KDM5C demethylase expression, altering H3K4me3 levels at the TIA1 locus and reducing stress granule (SG) formation in stromal CAFs, thereby supporting cancer cell survival under glucose starvation. |
Extracellular vesicle isolation, miR-33a overexpression/targeting of AGMAT in CAFs, KDM5C and H3K4me3 chromatin analysis, stress granule formation assays, ACO1 RNA-binding protein interaction studies |
Journal of extracellular vesicles |
Medium |
40903826
|