Evidence map›Paper›PMID 31605963›Full record

ArticleRedox biology2020

Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling.

Wen Shen, Chao Gao, Ramon Cueto, Lu Liu, Hangfei Fu, Ying Shao, William Y Yang, Pu Fang, Eric T Choi, Qinghua Wu and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 6% of its field
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

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.

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  16. The Homocysteine S-Methyltransferase Family and Functional Analysis ofJournal of agricultural and food chemistry · 2025
    Article
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9 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 2 countries.

Wen ShenDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Chao GaoCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Ramon CuetoCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Lu LiuCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Hangfei FuCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Ying ShaoCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
William Y YangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Pu FangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Eric T ChoiCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; Division of Vascular & Endovascular Surgery, Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Qinghua WuDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Electronic address: ncwqh@163.com.
Xiaofeng YangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Hong WangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA. Electronic address: hongw@temple.edu.
Temple University · USNanchang University · CN

Funding

CD40 monocyte in chronic kidney diseaseR01DK113775 · NIDDK · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2017 to 2021
$3.3M
Hyperhomocysteinemia and HDL MetabolismR01HL117654 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2013 to 2017
$3.0M
Caspase-1 activation mediates chronic kidney disease-accelerated atherosclerosisR01HL131460 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI CHOI, ERIC T., WANG, HONG · 2016 to 2019
$2.8M
The roles of miR-155 in regulating atherosclerosis and metabolically healthy obesityR01HL138749 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2017 to 2020
$2.6M
IL-35 inhibits gut microbiota-produced uremic toxin-accelerated endothelial cell activationR01HL147565 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2019 to 2022
$2.6M
NADHP Oxidase-mediated MC differentiation & Endothelial Dysfunction in HHcyR01HL110764 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2011 to 2015
$2.5M
Atherogenic roles of complement systemR01HL130233 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI QIN, XUEBIN, WANG, HONG · 2016 to 2019
$2.5M
IL-35 suppression of endothelial cell activation and atherosclerosisR01HL132399 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2017 to 2020
$2.3M
HHcy-induced Inflammatory Monocyte and Macrophage Differentiation in DiabetesR01DK104116 · NIDDK · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2015 to 2019
$2.2M
Role of HHcy in diabetic vascular diseaseR01HL082774 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2006 to 2010
$1.8M
NHLBI NIH HHS R01 HL082774NHLBI NIH HHS R01 HL110764NHLBI NIH HHS R01 HL117654NHLBI NIH HHS R01 HL130233NHLBI NIH HHS R01 HL131460NHLBI NIH HHS R01 HL132399NHLBI NIH HHS R01 HL138749NHLBI NIH HHS R01 HL147565NIDDK NIH HHS R01 DK104116NIDDK NIH HHS R01 DK113775
6 · The paper itself

Abstract

Homocysteine-Methionine (HM) cycle produces universal methyl group donor S-adenosylmethione (SAM), methyltransferase inhibitor S-adenosylhomocysteine (SAH) and homocysteine (Hcy). Hyperhomocysteinemia (HHcy) is established as an independent risk factor for cardiovascular disease (CVD) and other degenerative disease. We selected 115 genes in the extended HM cycle (31 metabolic enzymes and 84 methyltransferases), examined their protein subcellular location/partner protein, investigated their mRNA levels and mapped their corresponding histone methylation status in 35 disease conditions via mining a set of public databases and intensive literature research. We have 6 major findings. 1) All HM metabolic enzymes are located only in the cytosol except for cystathionine-β-synthase (CBS), which was identified in both cytosol and nucleus. 2) Eight disease conditions encountered only histone hypomethylation on 8 histone residues (H3R2/K4/R8/K9/K27/K36/K79 and H4R3). Nine disease conditions had only histone hypermethylation on 8 histone residues (H3R2/K4/K9/K27/K36/K79 and H4R3/K20). 3) We classified 9 disease types with differential HM cycle expression pattern. Eleven disease conditions presented most 4 HM cycle pathway suppression. 4) Three disease conditions had all 4 HM cycle pathway suppression and only histone hypomethylation on H3R2/K4/R8/K9/K36 and H4R3. 5) Eleven HM cycle metabolic enzymes interact with 955 proteins. 6) Five paired HM cycle proteins interact with each other. We conclude that HM cycle is a key metabolic sensor system which mediates receptor-independent metabolism-associated danger signal recognition and modulates SAM/SAH-dependent methylation in disease conditions and that hypomethylation on frequently modified histone residues is a key mechanism for metabolic disorders, autoimmune disease and CVD. We propose that HM metabolism takes place in the cytosol, that nuclear methylation equilibration requires a nuclear-cytosol transfer of SAM/SAH/Hcy, and that Hcy clearance is essential for genetic protection.

Indexed as

Gene Regulatory NetworksCytosolHistonesHomocysteineHumansHyperhomocysteinemiaMethionineMethylationProtein Interaction MapsProtein TransportHistonesHomocysteineMethionineHomocysteine-methionine cycleMetabolic sensorSAM/SAH-dependent methylation

Identifiers

PMID31605963
PMCPMC6812029
OpenAlexW2972766840

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.