Gamma glutamyl transpeptidase (GGT)
Gamma glutamyl transpeptidase is an enzyme that is primarily found in the liver and is a marker of liver function. Elevated levels may indicate liver damage or disease, especially alcohol-related liver disease.
iollo markers that associate with Gamma glutamyl transpeptidase (GGT)
Alanine
Alanine is an amino acid that can feed into the glutamic acid pool. Elevated alanine and GGT may reflect increased amino acid catabolism and liver dysfunction.
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J. H. Jeong, S. Jung, K. N. Kim. Alanine aminotransferase, γ-glutamyltransferase (GGT) and all-cause mortality: population-based study. Scientific Reports (2021). https://www.nature.com/articles/s41598-021-82981-z
J. H. Jeong, S. Jung, K. N. Kim. Considering serum alanine aminotransferase and gamma-glutamyltransferase levels together strengthen the prediction of impaired fasting glucose risk: a cross-sectional and longitudinal study. Scientific Reports (2021). https://www.nature.com/articles/s41598-021-82981-z
Aspartic Acid
Aspartic acid is a precursor for glutamine and glutamic acid synthesis. Increased demand for these amino acids for glutathione production may lower aspartic acid when GGT is high.
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M.B. West, S. Wickham, L.M. Quinalty et al.. Gamma-glutamyl transpeptidase: redox regulation and drug metabolism. Free Radical Biology and Medicine (2011). https://doi.org/10.1016/j.freeradbiomed.2011.03.021
Hsu, B.Y.L., Foreman, J.W., Corcoran, S.M. et al.. Absence of a role of gamma-glutamyl transpeptidase in the transport of amino acids by rat renal brushborder membrane vesicles. Journal of Membrane Biology (1984). https://doi.org/10.1007/BF01868772
Cysteine
Cysteine is a rate-limiting precursor for glutathione synthesis. GGT-mediated glutathione breakdown increases the demand for cysteine to replenish glutathione levels. Cysteine depletion can increase GGT.
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Whitfield JB. Gamma-Glutamyl Transpeptidase. Critical Reviews in Clinical Laboratory Sciences (2001). https://www.ncbi.nlm.nih.gov/pubmed/11720861
Tateishi N, Nishino H. The Role of Gamma-Glutamyl Transpeptidase in the Regulation of Cellular Redox Status. Journal of Biochemistry (2007). https://www.ncbi.nlm.nih.gov/pubmed/17222151
West MB, Wickham S, Quinalty LM, Pavlovicz RE, Li C, Hanigan MH. Gamma-Glutamyl Transpeptidase: Redox Regulation and Drug Metabolism. Journal of Biological Chemistry (2011). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388159/
Griffith OW, Meister A. Gamma-Glutamyl Transpeptidase Is a Glutathionase That Enables Cells to Use Extracellular Glutathione as a Source of Cysteine. Proceedings of the National Academy of Sciences (1985). https://www.ncbi.nlm.nih.gov/pubmed/3839049
Cystine
Cystine is the disulfide form of cysteine and influences glutathione status. Increased glutathione demand and breakdown by GGT may shift the balance from cysteine to cystine.
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References
M.B. West, S. Wickham, L.M. Quinalty, et al.. Gamma-Glutamyl Transpeptidase: Redox Regulation and Drug Disposition. Journal of Biological Chemistry (2011). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388159/
J.E.A. Wolff, G. Münstermann, K. Grebenkämper, et al.. Gamma-Glutamyl Transpeptidase Does Not Act As a Cystine Transporter in Brain Microvessels. Neurochemical Research (1998). https://doi.org/10.1023/A:1020726001310
Glutamic Acid
Glutamic acid is a substrate of GGT. Elevated GGT levels can indicate increased glutamic acid catabolism and are a marker of liver disease, alcohol abuse, and oxidative stress.
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J. T. Seibel, M. A. Brown. Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Homeostasis and Oxidative Stress. Antioxidants & Redox Signaling (2015). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620378/
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J. E. Everhart, E. C. Wright. Association of γ-glutamyl transferase (GGT) activity with treatment and clinical outcomes in chronic hepatitis C (HCV). PLOS ONE (2013). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624035/
ScienceDirect Topics. Gamma-Glutamyl Transpeptidase - an overview. ScienceDirect (nan). https://www.sciencedirect.com/topics/medicine-and-dentistry/gamma-glutamyl-transpeptidase
ScienceDirect Topics. Gamma-Glutamyltransferase - an overview. ScienceDirect (nan). https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/gamma-glutamyltransferase
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Y. Chang, H. Lee, T. J. Song. Association of gamma-glutamyl transferase variability with risk of venous thrombosis. Scientific Reports (2023). https://www.nature.com/articles/s41598-023-34368-5
Glutamine
Glutamine is a precursor for glutathione synthesis. Increased demand for glutathione due to oxidative stress or detoxification can deplete glutamine and increase GGT levels as glutathione is broken down.
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“Orlowski, M.”. “Glutamine as a gamma-glutamyl donor for gamma-glutamyl transpeptidase”. “Life Sciences” (1983). https://www.sciencedirect.com/science/article/abs/pii/0024320583906823
[Dalton, RN], [Clark, JM], [Meakin, SO]. Gamma-Glutamyl Transferase: The Silent Partner?. Alcohol and Alcoholism (2010). https://www.tandfonline.com/doi/full/10.3109/15412555.2010.496819
[Wang, Y], [Xie, X], [Zhang, H], [Zhang, Y], [Li, M], [Zhang, Z]. Gamma-Glutamyltransferase Levels Are Associated With the Occurrence of Poststroke Cognitive Impairment. BMC Neurology (2022). https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02587-4
[Bujanda, LM], [González-Sánchez, R], [Gómez-Marcos, MA], [González-Périz, A]. Gamma-Glutamyl Transferase: A Novel Cardiovascular Risk Biomarker. Clinical Chemistry and Laboratory Medicine (2009). https://onlinelibrary.wiley.com/doi/10.1111/j.1751-7141.2009.00054.x
[Meakin, SO], [Clark, JM], [Dalton, RN]. Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Stress and Disease. Clinical Chemistry and Laboratory Medicine (2015). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620378/
[Wang, Y], [Xie, X], [Zhang, H], [Zhang, Y], [Li, M], [Zhang, Z]. A Systematic Review of Serum γ-Glutamyltransferase as a Biomarker of Oxidative Stress and Liver Disease. NCBI (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066142/
Glycine
Glycine is involved in glutathione synthesis. Altered glycine levels along with high GGT may indicate disrupted glutathione metabolism and oxidative stress, common in liver disease.
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M. Takeda, T. Kawamura, T. Sugimoto, Y. Kawabe, H. Saito, T. Kawamori, S. Kobayashi. “Frequently abnormal serum gamma-glutamyl transferase activity in some individuals without fatty liver ultrasound images”. BMC Gastroenterology (2020). https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-020-01369-x
Gao, H., et al.. Glycine-based treatment ameliorates NAFLD by modulating fatty acid metabolism. Journal of Hepatology (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982985/
Y. Kawabata, Y. Ogawa, T. Shimizu, T. Ishimura, Y. Tanaka. “Therapeutic Effects of Amino Acids in Liver Diseases”. Nutrients (2019). https://www.mdpi.com/2072-6643/11/5/1189
Zhong, Z., & Zhou, J.. Beneficial Effects of the Amino Acid Glycine. Nutrients (2016). https://www.researchgate.net/publication/303951608_Beneficial_Effects_of_the_Amino_Acid_Glycine
Lactic acid
Lactic acid buildup can occur during oxidative stress and hepatic dysfunction, conditions that also increase GGT levels. Lactic acid may be a marker of the underlying oxidative or hepatic pathology.
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Douglas S. Lee et al.. Gamma Glutamyl Transferase and Metabolic Syndrome, Cardiovascular Disease, and Mortality Risk: The Framingham Heart Study. Arteriosclerosis, Thrombosis, and Vascular Biology (2006). https://doi.org/10.1161/01.ATV.0000251993.20372.40
A. Patil, S. Kulkarni, S. Patil et al.. Is gamma-glutamyl transpeptidase a biomarker for oxidative stress in periodontitis?. Journal of Clinical and Diagnostic Research (2015). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439622/
Hernández-Rubio, A., Sanvisens, A., Bolao, F. et al.. Association of hyperuricemia and gamma glutamyl transferase as a marker of metabolic risk in alcohol use disorder. Sci Rep (2020). https://doi.org/10.1038/s41598-020-77013-1
Taurine
Taurine has antioxidant and hepatoprotective effects. Depletion of taurine may occur in conditions that increase oxidative stress and GGT levels, such as liver disease and alcoholism.
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Dawson, R. L., Harris, R. C., & Carpenter, D. O.. Taurine as a Natural Antioxidant: From Direct Antioxidant Effects to Oxidative Stress Modulation. Antioxidants (2019). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698923/
Al-Olayan, A. A., Al-Daihan, Y. A., Al-Othman, A. A., Al-Resayes, S. A., Al-Malki, M. A., & Al-Sultanb, A. A.. Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage. BioMed Research International (2015). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676695/
Al-Olayan, A. A., Al-Daihan, Y. A., Al-Othman, A. A., Al-Resayes, S. A., Al-Malki, M. A., & Al-Sultanb, A. A.. Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage. BioMed Research International (2015). https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0144509
Xiaojun Wu, Jing Zhou, Xinyue Zhang, Xiaoyun Zhang, Ying Zhang, Qingqing Zhang, Li Wang, Xin Zhang, Yue Zhang, Xiaoyan Li, Xiaohong Wang, Ying Zhang, Xueqing Yu. Taurine Ameliorates Tunicamycin-Induced Liver Injury by Regulating ER Stress and Lipid Metabolism. Frontiers in Pharmacology (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951380/
Sreeja, P. R., & Sreeja, V. P.. Hepatoprotective and antioxidant activities of fruit pulp of Limonia acidissima Linn. Journal of Chemical and Pharmaceutical Research (2016). https://www.researchgate.net/publication/285908767_Hepatoprotective_and_antioxidant_activities_of_fruit_pulp_of_Limonia_acidissima_linn
Yuka Sugimoto, Hiroshi Kawamura, Masato Yamazaki, Shinobu Suzuki, Toshihisa Ito. Taurine treatment prevents derangement of the hepatic γ-glutamyl cycle and oxidative stress in aged mice. The FASEB Journal (2018). https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201700586R
Kohei Kawaguchi, Takashi Ito, Masahiko Kawai, Hiroshi Kawamura, Masato Yamazaki, Toshikazu Yoshikawa, Shinobu Suzuki, Toshihisa Ito. Phase IV Prospective Clinical Study to Evaluate the Effect of Taurine on γ-Glutamyl transpeptidase (GGT) and other indicators of liver function, glucose metabolism, lipid profile, inflammation markers, and treatment. The Journal of Clinical Biochemistry and Nutrition (2014). https://aspenjournals.onlinelibrary.wiley.com/doi/abs/10.1177/0884533614533610