Affinage

AHCY

Adenosylhomocysteinase · UniProt P23526

Length
432 aa
Mass
47.7 kDa
Annotated
2026-06-09
70 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AHCY (S-adenosylhomocysteine hydrolase/SAHH) is an essential metabolic enzyme that clears S-adenosylhomocysteine (SAH), thereby controlling cellular methylation potential, and its activity is genetically required for early embryonic development, with loss being phenocopied by pharmacological SAHH inhibition or experimental SAH elevation (PMID:8168479). As a tetramer, its catalytic competence depends on precise active-site architecture: disease-associated missense mutations (R49C, D86G, A89V) reduce activity through disulfide-linked aggregation, charge disruption, or steric incompatibility, in several cases without disrupting tetramer assembly (PMID:19177456, PMID:18211827). Because SAH is the product-inhibitor that constrains methyltransferase activity, modulation of AHCY activity propagates to genome-wide methylation programs: SAH accumulation downregulates DNMT1/DNMT3b and reduces EZH2-dependent H3K27me3, reprogramming methylation at specific loci to control inflammasome activation in diabetic nephropathy (PMID:34119876), vascular smooth muscle cell phenotype switching and atherosclerotic plaque stability via KLF4/OCT4 (PMID:42131918), adipocyte differentiation (PMID:38064408), and regulatory T cell differentiation through Foxp3 demethylation (PMID:41527294). AHCY activity also sustains adenosine pools required for proliferation, and its loss triggers a DNA damage response in hepatocellular carcinoma (PMID:30228286), while supporting antioxidant and mitochondrial metabolism (PMID:39605416). Beyond the cytoplasm, AHCY is recruited to chromatin at sites of active transcription and replication, matching methylation demand to cell division (PMID:30854431), and its nucleocytoplasmic distribution is governed by terminal localization signals and interaction with its paralog AHCYL1 (PMID:28647132). AHCY additionally performs catalysis-independent moonlighting functions: an adenosine-induced AHCY dimer physically occludes the m6A demethylase FTO at residue Q86 to selectively raise mRNA m6A on lipogenic transcripts and drive tumorigenesis without affecting methionine catabolism (PMID:41549122), and AHCY couples to glycolysis through STIP1 and LDHA, with PRMT3-mediated LDHA methylation stabilizing AHCY against degradation (PMID:41163796). AHCY activity is regulated post-translationally by inhibitory lysine β-hydroxybutyrylation (PMID:41527294) and is the direct molecular target of multiple drugs — doxorubicin, triptolide, and DZNep — that cause SAH accumulation with downstream epigenetic and metabolic toxicity (PMID:36445716, PMID:41391368, PMID:32408898, PMID:28533090).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 High

    Established that AHCY enzymatic activity is not merely housekeeping but is genetically essential for the earliest stages of mammalian development.

    Evidence Homozygous Ahcy deletion in mice plus embryo culture with SAHase inhibitor and SAH-elevating metabolites

    PMID:8168479

    Open questions at the time
    • Does not resolve which methylation substrate (DNA/RNA/histone/protein) is the critical downstream target
    • Does not address tissue-specific requirements beyond inner cell mass
  2. 2009 High

    Defined how specific clinical missense mutations cripple catalysis, mapping residues required for activity and tetramer integrity.

    Evidence Recombinant expression, enzymatic assays, site-directed mutagenesis, reducing-agent and native PAGE for R49C/D86G (and earlier A89V, polymorphic isoforms)

    PMID:17164794 PMID:18211827 PMID:19177456

    Open questions at the time
    • Mutant biochemistry assayed in isolation, not in patient tissue
    • Does not connect each mutation to a specific organismal phenotype
  3. 2017 Medium

    Showed AHCY is not strictly cytoplasmic but shuttles to the nucleus under control of terminal localization signals and its paralog AHCYL1.

    Evidence GFP imaging, deletion mapping, BiFC, leptomycin B treatment, and AHCYL1 siRNA

    PMID:28647132

    Open questions at the time
    • Nuclear export receptor identity unknown (CRM1-independent)
    • Functional consequence of nuclear pool not directly demonstrated here
  4. 2019 Medium

    Provided the spatial logic for AHCY's function by placing it on chromatin at active transcription and replication sites, coupling methylation supply to cell-division demand.

    Evidence DNA-mediated chromatin pull-down (Dm-ChP) with mass spectrometry and genomic integration in pluripotent cells

    PMID:30854431

    Open questions at the time
    • Mechanism of chromatin recruitment unknown
    • Does not establish whether recruitment requires catalytic activity
  5. 2018 Medium

    Demonstrated AHCY sustains adenosine pools whose depletion triggers the DNA damage response, linking the enzyme to proliferative capacity.

    Evidence siRNA knockdown with proteomics/metabolomics, DNA damage and cell-cycle assays in HCC cells

    PMID:30228286

    Open questions at the time
    • Single cell type
    • Relative contribution of adenosine depletion vs SAH accumulation not dissected
  6. 2021 High

    Resolved a complete SAH-to-disease axis, showing AHCY loss raises SAH, suppresses EZH2/H3K27me3, derepresses EGR1, and drives TXNIP/NLRP3-mediated injury.

    Evidence SAHH knockout and downstream KO mice, pharmacological inhibition, ChIP, in vivo diabetic nephropathy model

    PMID:34119876

    Open questions at the time
    • Specific to renal/diabetic context
    • Does not address whether other methyltransferases are co-affected
  7. 2026 High

    Extended the SAH-methylation paradigm to vascular disease, dissecting how SAHH loss reprograms DNMT3b/TET-dependent methylation of KLF4 and OCT4 to destabilize plaques.

    Evidence Cell-type-specific SAHH knockout mice, whole-genome bisulfite sequencing, RNA-seq, ChIP, AMPK pathway analysis

    PMID:42131918

    Open questions at the time
    • Cell-type specificity (VSMC vs macrophage) mechanism incompletely explained
    • Human relevance from mouse model not established
  8. 2025 Medium

    Uncovered a catalysis-independent moonlighting role in which AHCY couples to glycolysis via STIP1 and LDHA and is reciprocally stabilized by PRMT3-mediated LDHA methylation.

    Evidence Reciprocal Co-IP, conformational and in vitro binding assays, PRMT3 methylation and ubiquitination assays, in vivo tumorigenesis

    PMID:41163796

    Open questions at the time
    • Direct vs indirect nature of AHCY-LDHA binding not fully resolved
    • Generalizability beyond the tumor model tested unknown
  9. 2026 High

    Defined the most mechanistically complete moonlighting function: an adenosine-induced AHCY dimer occludes FTO to selectively raise lipogenic-mRNA m6A independent of SAM metabolism.

    Evidence Dimerization and FTO-binding mutants retaining hydrolase activity, m6A-seq, targeted metabolomics, xenograft/PDX and AHCY knockout mice

    PMID:41549122

    Open questions at the time
    • Structural basis of the dimer-FTO interface at Q86 not solved
    • Physiological signals controlling adenosine-driven dimerization unclear
  10. 2026 Medium

    Identified β-hydroxybutyrylation as a metabolite-driven post-translational switch that inhibits AHCY and reprograms immune-cell methylation.

    Evidence Kbhb modification analysis, AHCY activity assays, pyrosequencing of Foxp3-TSDR, flow cytometry, IL-10 KO colitis model

    PMID:41527294

    Open questions at the time
    • Specific modified lysine residues and stoichiometry not detailed
    • Whether Kbhb affects tetramer or chromatin recruitment unknown
  11. 2025 Medium

    Established AHCY as a direct, druggable molecular target whose chemical engagement (doxorubicin, triptolide, DZNep) causes SAH accumulation and downstream toxicity or therapeutic effect.

    Evidence Chemoproteomics, SPR/CETSA binding, co-crystal structures, enzymatic inhibition, CNV/resistance analysis, overexpression rescue

    PMID:28533090 PMID:32408898 PMID:36445716 PMID:41391368

    Open questions at the time
    • Off-target binding of these compounds not fully excluded
    • Therapeutic window between desired and toxic SAH accumulation unclear
  12. 2023 Medium

    Linked partial AHCY deficiency to longevity through an AMPK/DAF-16 axis, showing modest SAH elevation can be beneficial in a context-dependent manner.

    Evidence CRISPR knock-in of pathogenic-equivalent variant in C. elegans, lifespan and metabolite assays, epistasis with AMPK/VRK-1/DAF-16

    PMID:38052822

    Open questions at the time
    • Invertebrate model; mammalian relevance unproven
    • Mechanism linking SAH to AMPK activation not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how AHCY's localization signals, catalytic activity, and its catalysis-independent moonlighting interactions (FTO, LDHA, AHCYL1, HIV-1 integrase) are integrated and prioritized within a single cell.
  • No structural model unifying tetramer, adenosine-driven dimer, and partner-binding states
  • Recruitment signals coordinating chromatin vs cytoplasmic vs glycolytic pools undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140096 catalytic activity, acting on a protein 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-8953854 Metabolism of RNA 1
Partners
AHCYL1FTOLDHAPRMT3RACK1STIP1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 The Ahcy gene (encoding S-adenosylhomocysteine hydrolase/SAHase) is required for early embryonic development; homozygous deletion of Ahcy in mice leads to embryonic death between the late blastocyst and early implantation stages. Treatment of cultured embryos with the SAHase inhibitor 3-deazaaristeromycin or with metabolites that elevate cellular SAH inhibited inner cell mass development, indicating that loss of SAHase activity is sufficient to explain lethality. Genetic deletion mapping, SAHase RNA/protein detection in blastocysts and ES cells, embryo culture with pharmacological SAHase inhibitor The EMBO journal High 8168479
2008 AHCY-like proteins contain an IRBIT domain that serves as an anchor targeting them to cytoplasmic partners, enabling regulation of intracellular Ca2+ via the IP3 receptor and intracellular pH via Na+/HCO3- cotransporters; inactivation of the IRBIT domain induces nuclear translocation and modulation of AHCY activity. Review/synthesis of functional data including (de)phosphorylation, proteolysis, and protein–protein interaction studies reported in primary literature BioEssays Low 18536033
2009 Two novel missense mutations in AHCY (p.Arg49Cys and p.Asp86Gly) dramatically reduce enzymatic activity. p.Arg49Cys forms intermolecular disulfide bonds creating macromolecular structures preventable by DTT. p.Asp86Gly forms enzymatically inactive aggregates; restoring a negative charge at position 86 (Gly→Glu) recovers ~70% of wild-type activity, whereas introducing positively charged or uncharged residues does not, establishing that the negative charge at residue 86 is important for catalytic activity. Recombinant protein expression, enzymatic activity assay, site-directed mutagenesis, reducing agent treatment, native PAGE Human mutation High 19177456
2008 The A89V mutation in AHCY reduces enzymatic activity by ~70%, decreases thermal stability (unfolding temperature reduced by 5.5°C), and alters overall charge of the tetrameric complex without disrupting tetramer assembly. The mechanism involves steric incompatibility between Val89 and Thr84; substituting Thr84→Ser84 (smaller residue, similar chemistry) in the A89V background restores most catalytic activity, while introducing bulkier residues (Lys84, Gln84) inactivates wild-type protein. Recombinant protein expression, enzymatic activity assay, circular dichroism, gel filtration, native PAGE, site-directed mutagenesis Biochemical and biophysical research communications High 18211827
2006 Two polymorphic AHCY isoforms (SAHH-2, R38W; SAHH-3, G123R) have slightly reduced enzymatic activity (≤6% decrease) and reduced thermal stability compared to wild-type, but no major changes in catalytic rates, as determined by recombinant protein analysis. Recombinant wild-type and polymorphic protein expression, enzymatic activity assay, circular dichroism European journal of human genetics Medium 17164794
2017 Disease-causing AHCY mutations alter the nucleocytoplasmic distribution of AHCY protein compared to wild-type. Endogenous AHCY localizes to both cytoplasm and nucleus; nuclear export is not sensitive to leptomycin B. Systematic deletion mapping identified two regions (at both termini) contributing to nuclear localization, implying interactions with multiple proteins. AHCY interacts with its paralog AHCYL1 (SAHH-like-1) in vivo, and silencing AHCYL1 moderately inhibits nuclear export of endogenous AHCY. Fluorescence microscopy with GFP-tagged constructs, systematic deletion analysis, bimolecular fluorescence complementation (BiFC), leptomycin B treatment, siRNA knockdown European journal of cell biology Medium 28647132
2018 AHCY knockdown in hepatocellular carcinoma cells causes adenosine depletion, which activates the DNA damage response (DDR), leading to cell cycle arrest, decreased proliferation, and DNA damage, establishing a functional link between AHCY enzymatic activity and maintenance of adenosine pools required for cell proliferation. siRNA knockdown, multi-omics (proteomics + metabolomics), DNA damage assays, cell cycle analysis Scientific reports Medium 30228286
2019 AHCY is recruited to chromatin in proliferating embryonic stem cells and localizes to sites of active transcription and replication, correlating with demands for DNA, RNA, and histone methylation. Chromatin pull-down (Dm-ChP) identified AHCY as a chromatin-bound protein, and integration with genomic/functional data revealed a role for AHCY in gene activation and ribosomal protein production linked to cell division during early embryonic development. DNA-mediated chromatin pull-down (Dm-ChP), mass spectrometry, genomic integration, functional assays in pluripotent cells Science advances Medium 30854431
2011 The geminivirus betasatellite protein βC1 directly interacts with plant SAHH (S-adenosylhomocysteine hydrolase) and inhibits its enzymatic activity in vitro, thereby suppressing methylation-mediated transcriptional gene silencing (TGS). Interaction was established by yeast two-hybrid and bimolecular fluorescence complementation. Yeast two-hybrid, bimolecular fluorescence complementation, in vitro SAHH enzyme activity assay, plant transient expression PLoS pathogens Medium 22028660
2014 SAHH overexpression in esophageal squamous cell carcinoma (ESCC) cells promotes apoptosis, inhibits cell migration and adhesion (but does not affect proliferation or cell cycle). Co-immunoprecipitation demonstrated an interaction between SAHH and RACK1 (receptor for activated C kinase 1), and SAHH overexpression increased RACK1 protein levels. Overexpression in cell lines, apoptosis/migration/adhesion assays, co-immunoprecipitation, Western blotting Molecular biology reports Low 24430301
2017 The reversible SAHH inhibitor DZ2002 suppresses TLR-mediated APC responses in lupus-prone mice, decreasing pathogenic Th17 cell development and inhibiting STAT3 phosphorylation and JNK/NF-κB signaling in splenocytes, establishing that SAHH activity is required for TLR-driven inflammatory signaling. Pharmacological inhibition (DZ2002) in vivo and ex vivo, ELISA, Western blot for phosphorylation, flow cytometry, BMDC-T cell co-culture Acta pharmacologica Sinica Medium 24374810
2016 Metformin upregulates microRNA let-7 via AMPK activation, leading to degradation of the lncRNA H19, which normally binds to and inactivates SAHH. H19 knockdown activates SAHH, enabling DNMT3B-mediated methylation of a subset of genes, establishing H19 as a direct negative regulator of SAHH activity and linking SAHH to genome-wide DNA methylation changes. Cell line experiments, miRNA overexpression, lncRNA knockdown, DNMT activity assay, genome-wide methylation analysis, patient tissue validation Oncogene Medium 27775072
2021 SAHH inhibition (via ADA inhibitor or heterozygous knockout) causes SAH accumulation, which reduces EZH2 histone methyltransferase activity and decreases H3K27me3 enrichment at the EGR1 promoter. EGR1 is thereby activated and binds to the TXNIP promoter, inducing TXNIP-mediated oxidative stress and NLRP3 inflammasome activation, aggravating diabetic nephropathy. Pharmacological inhibition, SAHH knockout mice, NLRP3/TXNIP KO mice, ChIP, Western blot, gene expression analysis, in vivo diabetic nephropathy model Redox biology High 34119876
2020 AHCY copy number amplification (~30-fold) in a DZNep-resistant B-cell lymphoma clone results in strong overexpression of AHCY at both mRNA and protein levels, and persists in DZNep-free medium. This establishes AHCY as a direct target of DZNep (which blocks SAH hydrolysis), and its amplification as a resistance mechanism to the indirect EZH2 inhibitor. Copy number variation assay (OncoScan, TaqMan), FISH, Western blot, IHC, metabolomics in resistant vs. wild-type lymphoma cells BMC cancer Medium 32408898
2022 Doxorubicin (DOX) directly binds to AHCY in living cells, leading to accumulation of S-adenosylhomocysteine. This was established by photoaffinity labeling chemoproteomics followed by validation with cellular thermal shift assay, affinity competitive pull-down, biochemical enzyme inhibition assay, and siRNA knockdown. Photoaffinity labeling chemoproteomics, cellular thermal shift assay, affinity competitive pull-down, biochemical enzyme activity assay, siRNA knockdown, untargeted metabolomics Analytical chemistry Medium 36445716
2023 In C. elegans, introduction of the AHCY-1 Y145C variant (corresponding to human pathogenic Y143C mutation) impairs SAH hydrolysis, leading to moderately increased SAH and decreased SAM levels. This partial AHCY-1 deficiency extends lifespan in a manner dependent on AMPK, its activator VRK-1, and the transcription factor DAF-16, linking AHCY activity to aging via the AMPK/DAF-16 pathway. CRISPR knock-in of AHCY-1 Y145C in C. elegans, lifespan assay, SAM/SAH metabolite measurement, genetic epistasis with AMPK/VRK-1/DAF-16 mutants npj aging Medium 38052822
2025 STIP1 (stress-induced phosphoprotein 1) physically interacts with AHCY and changes its conformation upon binding. The STIP1-AHCY interaction facilitates AHCY binding to lactate dehydrogenase A (LDHA), stimulating glycolysis. Additionally, AHCY recruits PRMT3 to methylate LDHA at R106, which inhibits ubiquitination-mediated AHCY degradation, establishing a moonlighting function for AHCY in regulating glycolytic metabolism via protein–protein interactions independent of its canonical SAH hydrolase activity. Co-immunoprecipitation, conformational change analysis, in vitro binding assays, PRMT3 methylation assay, ubiquitination assay, in vivo mouse tumorigenesis model Exploration (Beijing, China) Medium 41163796
2025 Purified recombinant AHCY co-precipitates in vitro with HIV-1 integrase, indicating direct physical interaction. AHCY knockdown in human cells enhances HIV-1 reverse transcription efficiency (but not proviral transcription), establishing AHCY as a negative regulator of HIV-1 reverse transcription at early replication stages, a function in which integrase is also involved. In vitro co-precipitation of recombinant proteins, siRNA knockdown, HIV-1-based pseudovirus transduction assay, stage-specific replication assays Biochemistry. Biokhimiia Medium 41354074
2026 The AHCY-adenosine complex increases mRNA m6A levels in a non-global, sequence-specific manner (at VWDRACH motifs) to promote fatty acid biosynthesis genes (ACACA, SCD1) and tumorigenesis. Mechanistically, adenosine binds AHCY to promote its dimerization; AHCY dimers physically obstruct binding of the m6A demethylase FTO at Q86, preventing FTO from demethylating target mRNAs. AHCY mutants that cannot dimerize or bind FTO but retain hydrolase activity suppress lipogenesis and tumor growth without affecting methionine catabolism, demonstrating a SAM-independent epigenetic function. Co-IP/binding assays, AHCY dimerization mutants, FTO-binding mutants, m6A sequencing, targeted metabolomics, in vivo tumor xenograft and patient-derived xenograft models, AHCY knockout mice Cell research High 41549122
2024 MAT2A or AHCY knockdown/inhibition in glioblastoma cells induces oxidative stress, impairs mitochondrial respiration (specifically spare respiratory capacity), reduces cystathionine (a redox buffer), alters lipid and amino acid metabolism, prevents DNA damage protection, and reduces GBM cell survival, establishing AHCY as required for maintaining antioxidant metabolism and oxidative phosphorylation in GBM. Genetic knockdown (siRNA), pharmacological inhibition, mitochondrial respiration (Seahorse), targeted metabolomics, cell viability assay bioRxivpreprint Medium 39605416
2026 β-hydroxybutyrate (BHB) induces lysine β-hydroxybutyrylation (Kbhb) of AHCY, inhibiting its enzymatic activity and causing SAH accumulation. This SAH accumulation downregulates DNMT1 activity and promotes demethylation of the Foxp3-TSDR region, enhancing Foxp3 transcription and regulatory T cell (Treg) differentiation. This establishes Kbhb as a post-translational modification that regulates AHCY activity. Metabolomics, transcriptomics, pyrosequencing, Kbhb modification analysis, AHCY activity measurement, flow cytometry for Tregs, in vivo IL-10 KO colitis model Journal of Crohn's & colitis Medium 41527294
2025 Triptolide (TP) binds directly to AHCY with high affinity (KD = 3.179 × 10⁻¹¹ M), inhibiting its activity and causing SAH accumulation, DNA hypomethylation, metabolic dysfunction, and oxidative stress in liver cells. AHCY overexpression attenuates TP-induced hepatotoxicity, establishing AHCY as the direct molecular target mediating triptolide liver injury. Chemical proteomics, metabolomics, molecular dynamics simulation, surface plasmon resonance (SPR), AHCY overexpression rescue Phytomedicine Medium 41391368
2024 AHCY inhibition in mouse and human adipocyte progenitor cells reduces proliferation and impairs differentiation into mature adipocytes. Global DNA methylation profiling showed AHCY inhibition alters CpG methylation at genes involved in fat cell differentiation and cellular growth pathways, establishing AHCY activity as necessary for adipogenic proliferation and differentiation. Pharmacological inhibition (AdOx), siRNA knockdown, proliferation assays, differentiation assays (ALP, adipogenic markers), genome-wide DNA methylation profiling Adipocyte Medium 38064408
2026 VSMC-specific (but not macrophage-specific) knockout of SAHH in ApoE-deficient mice induces VSMC phenotype switching and decreases atherosclerotic plaque stability. Mechanistically, SAHH deficiency causes SAH accumulation, which inhibits DNMT3b, leading to hypomethylation of the KLF4 promoter and KLF4 upregulation. KLF4 then reactivates OCT4-mediated VSMC migration via TET1-mediated hydroxymethylation of the OCT4 promoter. AMPK inhibition by SAHH deletion also downregulates TET2-mediated KLF4 promoter hydroxymethylation. Cell-type-specific SAHH knockout mice, whole-genome bisulfite sequencing, RNA sequencing, ChIP, AMPK pathway analysis, plaque stability assessment, Western blot Arteriosclerosis, thrombosis, and vascular biology High 42131918
2017 High-throughput mass spectrometry screening identified small molecules that competitively inhibit AHCY at the SAH binding site. Co-crystal structures of hit compounds with AHCY confirmed binding in the SAH site, and hit compounds increased intracellular SAH levels and inhibited growth of HCT116 cells, functionally validating AHCY enzymatic activity as an anti-tumor target. High-throughput enzymatic assay (RapidFire MS), co-crystal structure determination, cellular SAH measurement, cell growth inhibition assay Biochemical and biophysical research communications High 28533090

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Suppression of methylation-mediated transcriptional gene silencing by βC1-SAHH protein interaction during geminivirus-betasatellite infection. PLoS pathogens 177 22028660
2016 Metformin alters DNA methylation genome-wide via the H19/SAHH axis. Oncogene 116 27775072
2021 Epigenetic regulation of TXNIP-mediated oxidative stress and NLRP3 inflammasome activation contributes to SAHH inhibition-aggravated diabetic nephropathy. Redox biology 115 34119876
1994 The mouse lethal nonagouti (a(x)) mutation deletes the S-adenosylhomocysteine hydrolase (Ahcy) gene. The EMBO journal 105 8168479
2007 Homocysteine-mediated expression of SAHH, DNMTs, MBD2, and DNA hypomethylation potential pathogenic mechanism in VSMCs. DNA and cell biology 74 17688412
2021 Functional and Pathological Roles of AHCY. Frontiers in cell and developmental biology 69 33869213
2017 Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-α/IFN-γ-induced inflammatory response in keratinocytes and T cell-derived IL-17. Pharmacological research 47 29155016
2019 Chromatin capture links the metabolic enzyme AHCY to stem cell proliferation. Science advances 44 30854431
2018 Knock-down of AHCY and depletion of adenosine induces DNA damage and cell cycle arrest. Scientific reports 41 30228286
2013 Effects of the crinivirus coat protein-interacting plant protein SAHH on post-transcriptional RNA silencing and its suppression. Molecular plant-microbe interactions : MPMI 41 23697374
2018 Long non-coding RNA H19/SAHH axis epigenetically regulates odontogenic differentiation of human dental pulp stem cells. Cellular signalling 39 30165103
2008 The IRBIT domain adds new functions to the AHCY family. BioEssays : news and reviews in molecular, cellular and developmental biology 36 18536033
2009 S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome. Human mutation 28 19177456
2022 Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice. Oxidative medicine and cellular longevity 26 35927991
2023 Exosomal circ-AHCY promotes glioblastoma cell growth via Wnt/β-catenin signaling pathway. Annals of clinical and translational neurology 24 37150844
2012 Heterologous expression of sahH reveals that biofilm formation is autoinducer-2-independent in Streptococcus sanguinis but is associated with an intact activated methionine cycle. The Journal of biological chemistry 22 22942290
2017 Mutations in S-adenosylhomocysteine hydrolase (AHCY) affect its nucleocytoplasmic distribution and capability to interact with S-adenosylhomocysteine hydrolase-like 1 protein. European journal of cell biology 20 28647132
2013 Therapeutic effects of DZ2002, a reversible SAHH inhibitor, on lupus-prone NZB×NZW F1 mice via interference with TLR-mediated APC response. Acta pharmacologica Sinica 20 24374810
2020 DNA methylation of AHCY may increase the risk of ischemic stroke. Bosnian journal of basic medical sciences 17 32020847
2012 Mice deficient in cystathionine beta synthase display increased Dyrk1A and SAHH activities in brain. Journal of molecular neuroscience : MN 15 22700376
2021 Proteomics study of colorectal cancer and adenomatous polyps identifies TFR1, SAHH, and HV307 as potential biomarkers for screening. Journal of proteomics 14 33915303
2017 Identification of AHCY inhibitors using novel high-throughput mass spectrometry. Biochemical and biophysical research communications 14 28533090
2019 SAHH and SAMS form a methyl donor complex with CCoAOMT7 for methylation of phenolic compounds. Biochemical and biophysical research communications 12 31582217
2014 Overexpression of S-adenosylhomocysteine hydrolase (SAHH) in esophageal squamous cell carcinoma (ESCC) cell lines: effects on apoptosis, migration and adhesion of cells. Molecular biology reports 12 24430301
1989 Isozyme and DNA analysis of human S-adenosyl-L-homocysteine hydrolase (AHCY). Annals of human genetics 12 2574561
2016 Abnormal Hypermethylation at Imprinting Control Regions in Patients with S-Adenosylhomocysteine Hydrolase (AHCY) Deficiency. PloS one 11 26974671
2009 The S-adenosyl-L-homocysteine hydrolase gene ahcY of Agrobacterium radiobacter K84 is required for optimal growth, antibiotic production, and biocontrol of crown gall disease. Molecular plant-microbe interactions : MPMI 10 19445596
2020 A Turkish patient with novel AHCY variants and presumed diagnosis of S-adenosylhomocysteine hydrolase deficiency. American journal of medical genetics. Part A 9 31957987
2008 S-Adenosylhomocysteine hydrolase (AdoHcyase) deficiency: enzymatic capabilities of human AdoHcyase are highly effected by changes to codon 89 and its surrounding residues. Biochemical and biophysical research communications 9 18211827
2019 Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone mice by downregulating renal α-actinin-4 expression and stabilizing integrin-cytoskeleton linkage. Arthritis research & therapy 8 30696480
2022 The long non-coding RNA lncMYOZ2 mediates an AHCY/MYOZ2 axis to promote adipogenic differentiation in porcine preadipocytes. BMC genomics 7 36221052
2022 Discovery of AHCY as an Off-Target of Doxorubicin by Integrative Analysis of Photoaffinity Labeling Chemoproteomics and Untargeted Metabolomics. Analytical chemistry 7 36445716
2018 Non-Immune Hydrops, Hypotonia, Encephalopathy, and Liver Failure with Novel Compound Heterozygous AHCY Mutations. Neonatology 7 30121674
2006 Functional analysis of human S-adenosylhomocysteine hydrolase isoforms SAHH-2 and SAHH-3. European journal of human genetics : EJHG 7 17164794
2021 Coordinated expression of Jumonji and AHCY under OCT transcription factor control to regulate gene methylation in wood frogs during anoxia. Gene 6 33887369
2016 Structural insight into binding mode of inhibitor with SAHH of Plasmodium and human: interaction of curcumin with anti-malarial drug targets. Journal of chemical biology 6 27698948
2024 Ultrasound-targeted microbubble technology facilitates SAHH gene delivery to treat diabetic cardiomyopathy by activating AMPK pathway. iScience 5 38303706
2024 Genome-wide DNA methylation regulated by AHCY through SAM / SAH axis promotes psoriasis pathogenesis. Journal of dermatological science 5 39521647
2023 SAM, SAH and C. elegans longevity: insights from a partial AHCY deficiency model. npj aging 5 38052822
2020 Acquired resistance to DZNep-mediated apoptosis is associated with copy number gains of AHCY in a B-cell lymphoma model. BMC cancer 5 32408898
2019 Molecular cloning, characterization and expression analysis of S- adenosyl- L-homocysteine hydrolase (SAHH) during the pathogenic infection of Litopenaeus vannamei by Vibrio alginolyticus. Fish & shellfish immunology 5 30849500
2013 S-adenosyl homocysteine hydrolase (SAHH) accelerates flagellar regeneration in Dunaliella salina. Current microbiology 5 23532254
1987 Family and population studies of SAHH and ADA polymorphisms. A possible pitfall in the ascertainment of SAHH electrophoretic phenotypes. Annals of human genetics 5 3447513
1984 Gene frequencies of S-adenosylhomocysteine hydrolase (SAHH) in a Japanese population. Human genetics 5 6500572
2025 In-silico Study of an Inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) of Naegleria fowleri using Molecular Docking, Density Functional Theory (DFT), and Molecular Dynamics (MD) Simulation. Molecular biotechnology 4 39948258
2023 Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells. Adipocyte 4 38064408
2023 Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 4 38070246
2002 Characterization and chromosome assignment of the porcine AHCY gene for S-adenosylhomocysteine hydrolase. Cytogenetic and genome research 4 12438749
2025 STIP1 drives Metabolic Reprogramming in Esophageal Squamous Cell Carcinoma via AHCY-LDHA Axis. Exploration (Beijing, China) 3 41163796
2024 MAT2a and AHCY inhibition disrupts antioxidant metabolism and reduces glioblastoma cell survival. bioRxiv : the preprint server for biology 3 39605416
2020 The values of AHCY and CBS promoter methylation on the diagnosis of cerebral infarction in Chinese Han population. BMC medical genomics 3 33138824
1987 [Gene frequencies of the enzymes ALADH, GOT2, GPT, PGM3, SAHH and UMPK in a Swiss population]. Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur 3 2821877
2026 The AHCY-adenosine complex rewires mRNA methylation to enhance fatty acid biosynthesis and tumorigenesis. Cell research 2 41549122
2022 Whole-genome analysis of CGS, SAHH, SAMS gene families in five Rosaceae species and their expression analysis in Pyrus bretschneideri. PeerJ 2 35313526
1992 Kinetic properties of the common electrophoretic variants of human S-adenosylhomocysteine hydrolase (AHCY): the effect of four nucleoside analogue inhibitors. Annals of human genetics 2 1586132
2026 AHCY: A metabolic gatekeeper at the interface of methylation, redox balance, and cellular stress response. The Journal of biological chemistry 1 41638428
2025 Impact of DLX3/SAHH axis on osteogenic differentiation of BMSCs in alveolar bone. Journal of oral biosciences 1 40180282
2022 Effects of H19/SAHH/DNMT1 on the oxidative DNA damage related to benzo[a]pyrene exposure. Environmental science and pollution research international 1 36098921
2020 Comparing recombinant MPB70/SahH and native 20-kDa protein for detecting bovine tuberculosis using ELISA. The Journal of veterinary medical science 1 33055466
2014 Crystallization and preliminary X-ray diffraction analysis of the S-adenosylhomocysteine hydrolase (SAHH) from Thermotoga maritima. Acta crystallographica. Section F, Structural biology communications 1 25372832
2026 Intermittent ketogenic diet promotes Treg differentiation and alleviates Crohn's disease via the β-hydroxybutyrate driven AHCY-DNMT1-Foxp3 axis. Journal of Crohn's & colitis 0 41527294
2026 Bioinformatics identification of adenosylhomocysteinase (AHCY) as a regulator of ferroptosis in nasopharyngeal carcinoma cells via the Hippo-Yes-associated protein (Hippo-YAP) pathway. Translational cancer research 0 41815160
2026 SAHH Deficiency Decreases Stability of Atherosclerotic Plaque and Induces VSMC Phenotype Switching via Epigenetic Upregulation of KLF4 and OCT4. Arteriosclerosis, thrombosis, and vascular biology 0 42131918
2025 The Role of AHCY Expression in Bladder Urothelial Carcinoma: A Bioinformatics and Experimental Analysis. Cancer management and research 0 40144861
2025 ASIP, AHCY and ITCH Genes Are Associated with the Coat Color of Local Goats (Capra hircus) of Southwestern China. Animals : an open access journal from MDPI 0 40646748
2025 Interaction between dietary nutrients related to one-carbon metabolism intakes and AHCY rs819173 polymorphism in the risk of gastric cancer: a case-control study in Korea. The British journal of nutrition 0 40859769
2025 Cellular Proteins Hsp60 and SAHH as Negative Regulators of the Early Stages of HIV-1 Replication. Biochemistry. Biokhimiia 0 41354074
2025 Integrative Chemical Proteomics and Metabolomics Identify AHCY as the Direct Target of Triptolide-induced Liver Injury. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41391368
2024 Dysmorphic Findings in SAHH Deficiency with a Novel Variant in the AHCY Gene. Molecular syndromology 0 39634240
2022 [Association among urinary polycyclic aromatic hydrocarbons metabolites, SAHH activity and H19 expression in coke oven workers]. Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 0 36510712

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