GGH

Last update 08 May 2025

Basic Info

Synonyms

Conjugase, folylpolygammaglutamyl hydrolase, Gamma-Glu-X carboxypeptidase

+ [4]

Introduction

Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free glutamate (PubMed:11005824, PubMed:8816764). May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.

100 Clinical Results associated with GGH

100 Translational Medicine associated with GGH

0 Patents (Medical) associated with GGH

363

Literatures (Medical) associated with GGH

06 Mar 2025·Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]

[Tissue and plasma proteomic signatures associated with the risk of gastric cancer].

Article

Author: Pan, K F ; Zhang, Y ; Li, X ; Yang, L X ; You, W C ; Xu, H M ; Ainiwaer, Kaosaier ; Li, W Q ; Zhang, J Y ; Zhou, T

Objective: To identify proteins associated with the risk of gastric cancer (GC) and build a protein risk score for risk prediction of GC based on proteomic analysis. Methods: Gastric mucosal proteomics data were used to construct Dataset One, comprising 94 GC cases and 230 individuals with different stages of gastric mucosal lesions. The GC cases were recruited from the National Upper Gastrointestinal Cancer Early Detection (UGCED) Program in Linqu, Shandong Province, as well as clinical patients from the Fifth Medical Center, General Hospital of PLA, and Peking University Cancer Hospital. Non-cancer individuals were enrolled from the National UGCED Program in Linqu and community screening programs at the Dongfang Hospital. All participants were pathologically confirmed. Multivariate logistic regression analysis was employed to identify gastric mucosal proteins significantly associated with GC risk. Subsequently, plasma proteomics data from the UK Biobank Pharma Proteomics Project (UKB-PPP) were used to construct Dataset Two, including 40 baseline GC cases and 47 933 non-cancer individuals, and Dataset Three, comprising 138 incident GC cases and 47 933 non-cancer individuals during a prospective follow-up period. In Dataset Two, multivariate logistic regression analysis was conducted to assess associations between plasma protein levels and baseline GC risk. In Dataset Three, multivariate Cox regression analysis was used to examine associations with the risk of incident GC. A poly-protein risk score (PRS) was developed using a weighted summation method based on protein effect sizes from Dataset Two. Its associations with GC risk and the progression of gastric mucosal lesions were evaluated using linear regression trend tests. Results: A total of 324, 47 973 and 48 071 participants were included in Datasets One, Two, and Three, respectively. Across the three datasets, the proportions of males and individuals aged>60 years were higher in the GC group than in the non-GC group (all P values<0.05). The follow-up period in Dataset Three had a M (P₂₅, P₇₅) of 14.47 (13.7, 15.2) years, with a median of 7.4 (4.6, 11.3) years for those who progressed to GC. Based on Dataset One, 2 524 tissue-differential proteins associated with GC risk were identified through multivariate logistic regression analysis adjusted for age and sex. Among these, seven proteins were consistently associated with GC risk across tissue and plasma levels in Datasets Two and Three, with consistent directions of association. Five proteins (MRC1, APOL1, BST2, PON2, and GGH) were positively associated with GC risk, while two (GSN and CLEC3B) were negatively associated. Analysis of the PRS based on these seven proteins showed that for each standard deviation increase in the tissue-derived PRS, the risk of GC increased by 6.26 times (95%CI: 4.02-9.75). In Dataset Two, each standard deviation increase in the plasma-derived PRS was associated with a 2.13-fold increase in GC risk (95%CI: 1.68-2.69). In the prospective cohort of Dataset Three, individuals in the high PRS group had a 2.27-fold higher risk of GC compared to the low PRS group (95%CI: 1.50-3.45). Moreover, each standard deviation increase in the plasma PRS was associated with a 57% higher risk of GC (HR=1.57, 95%CI: 1.34-1.84). Additionally, the tissue-derived PRS showed an increasing trend with the progression of gastric mucosal lesions. Conclusion: The tissue and plasma proteomics identified seven individual proteins that may indicate the risk of developing gastric cancer, showing the potential as biomarkers for aiding in the screening of gastric cancer.

01 Mar 2025·Gene

The regulation of the cell cycle and epithelial-mesenchymal transition through FUCA2/GGH signaling promotes the progression of lung adenocarcinoma

Article

Author: Guo, Jianqiang ; Liu, Yafeng ; Hu, Dong ; Wu, Jing ; Ma, Bingfeng ; Bai, Ying ; Yang, Xingyu ; Zhou, Jiawei ; Peng, Yuanyuan

The development of lung adenocarcinoma (LUAD) is intricately linked with cell cycle regulation and epithelial-mesenchymal transition (EMT). Our study, leveraging bioinformatics and database analysis, identified FUCA2 as a key gene influencing the prognosis and progression of LUAD. We observed that FUCA2 is highly expressed in LUAD and correlates with poor outcomes. Functionally, we assessed the role of this gene through cell cloning, scratch assays, transwell migration, and western blotting, revealing that FUCA2 knockdown significantly inhibits tumor cell proliferation and migration, downregulates the expression of cell cycle and EMT-related proteins, and markedly reduces tumor burden. Mechanistically, pathway enrichment analysis identified GGH as a downstream target of FUCA2. Knockdown of GGH similarly inhibits the proliferation, migration, and cell cycle progression of LUAD cells. FUCA2 upregulates GGH to modulate cell cycle and EMT in LUAD. Collectively, our findings indicate that the FUCA2/GGH axis promotes LUAD progression by regulating cell cycle and EMT.

14 Feb 2025·British Journal of Nutrition

Associations between skeletal muscle mass and elevated blood pressure are independent of body fat: a cross-sectional study in young adult women of African ancestry

Article

Author: Micklesfield, Lisa K ; Dlamini, Siphiwe N ; Norris, Shane A

AbstractAlthough research on the relationship between lean body mass and blood pressure (BP) has been inconsistent, most studies reported that measures of lean body mass are associated with a higher risk of hypertension. We explored relationships between body composition (fat and skeletal muscle mass) and BP in 1162 young adult African women. Dual-energy X-ray absorptiometry-derived measures of whole-body, central and arm fat mass were associated with higher systolic and diastolic BP, while leg fat percentage was associated with lower systolic and diastolic BP. However, only the associations with diastolic BP remained after adjusting for appendicular skeletal muscle mass (ASM). ASM was associated with higher systolic and diastolic BP, before and after adjusting for whole-body fat percentage and visceral adipose tissue. While there was no overlap in targeted proteomics of BP and body composition, REN was lower in the elevated BP than the normal BP group and was inversely associated with diastolic BP (false rate discovery adjusted P< 0·050). Several proteins were positively associated with both visceral adipose tissue and ASM (LEP, FABP4, IL6 and GGH) and negatively associated with both visceral adipose tissue and ASM (ACAN, CELA3A, PLA2G1B and NCAM1). NOTCH3, ART3, COL1A1, DKK3, ENG, NPTXR, AMY2B and CNTN1 were associated with lower visceral adipose tissue only, and IGFBP1 was associated with lower ASM only. While the associations between body fat and BP were not independent of skeletal muscle mass, the associations between muscle mass and BP were independent of overall and central adiposity in young adult African women. Future interventions targeting muscle mass should also monitor BP in this population.

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