Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2022 Volume 25 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2022 Volume 25 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review)

  • Authors:
    • Xingqi Meng
    • Huiqing Liu
    • Lixuan Peng
    • Weiguo He
    • Suyun Li
  • View Affiliations / Copyright

    Affiliations: Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, P.R. China
  • Article Number: 151
    |
    Published online on: March 2, 2022
       https://doi.org/10.3892/mmr.2022.12667
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

As an intermediate of the tricarboxylic acid cycle, also known as 2‑oxoglutarate, α‑ketoglutaric acid (AKG) plays an important role in maintaining physiological functions and cell metabolism. AKG is involved in both energy metabolism, and carbon and nitrogen metabolism; thus, exhibiting a variety of functions. Moreover, AKG plays an important role in various systems of the body. Results of previous research indicated that AKG may act as a regulator in the progression of a variety of diseases; thus, it exhibits potential as a novel drug for the clinical treatment of age‑related diseases. The present review aimed to summarize the latest research progress and potential clinical applications of AKG and provided novel directions and scope for future research.
View Figures

Figure 1

Figure 2

View References

1 

Xiao D, Zeng L, Yao K, Kong X, Wu G and Yin Y: The glutamine-alpha-ketoglutarate (AKG) metabolism and its nutritional implications. Amino Acids. 48:2067–2080. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Cunha RA: How does adenosine control neuronal dysfunction and neurodegeneration? J Neurochem. 139:1019–1055. 2016. View Article : Google Scholar : PubMed/NCBI

3 

de Medeiros HC, Constantin J, Ishii-Iwamoto EL and Mingatto FE: Effect of fipronil on energy metabolism in the perfused rat liver. Toxicol Lett. 236:34–42. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Jeevanandam M, Begay CK, Holaday NJ and Petersen SR: Nutritional and metabolic effects and significance of mild orotic aciduria during dietary supplementation with arginine or its organic salts after trauma injury in rats. Metabolism. 46:785–792. 1997. View Article : Google Scholar : PubMed/NCBI

5 

Legendre F, MacLean A, Appanna VP and Appanna VD: Biochemical pathways to alpha-ketoglutarate, a multi-faceted metabolite. World J Microbiol Biotechnol. 36:1232020. View Article : Google Scholar : PubMed/NCBI

6 

Valenzuela PL, Morales JS, Emanuele E, Pareja-Galeano H and Lucia A: Supplements with purported effects on muscle mass and strength. Eur J Nutr. 58:2983–3008. 2019. View Article : Google Scholar : PubMed/NCBI

7 

Niemiec T, Sikorska J, Harrison A, Szmidt M, Sawosz E, Wirth-Dzieciolowska E, Wilczak J and Pierzynowski S: Alpha-ketoglutarate stabilizes redox homeostasis and improves arterial elasticity in aged mice. J Physiol Pharmacol. 62:37–43. 2011.PubMed/NCBI

8 

Radzki RP, Bienko M, Filip R and Pierzynowski SG: The protective and therapeutic effect of exclusive and combined treatment with alpha-ketoglutarate sodium salt and ipriflavone on bone loss in orchidectomized rats. J Nutr Health Aging. 20:628–636. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Tomaszewska E, Swiatkiewicz S, Arczewska-Wlosek A, Wojtysiak D, Dobrowolski P, Domaradzki P, Świetlicka I, Donaldson J, Hułas-Stasiak M and Muszyński S: Alpha-Ketoglutarate: An effective feed supplement in improving bone metabolism and muscle quality of laying hens: A preliminary study. Animals (Basel). 10:24202020. View Article : Google Scholar : PubMed/NCBI

10 

Yang R, Wang X, Liu S, Zhang W, Wang P, Liu X, Ren Y, Tan X and Chi B: Bioinspired poly (ү-glutamic acid) hydrogels for enhanced chondrogenesis of bone marrow-derived mesenchymal stem cells. Int J Biol Macromol. 142:332–344. 2020. View Article : Google Scholar : PubMed/NCBI

11 

Tian Q, Bravo Iniguez A, Sun Q, Wang H, Du M and Zhu MJ: Dietary alpha-ketoglutarate promotes epithelial metabolic transition and protects against DSS-induced colitis. Mol Nutr Food Res. 65:e20009362021. View Article : Google Scholar : PubMed/NCBI

12 

Asadi Shahmirzadi A, Edgar D, Liao CY, Hsu YM, Lucanic M, Asadi Shahmirzadi A, Wiley CD, Gan G, Kim DE, Kasler HG, et al: Alpha-Ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metab. 32:447–456, e6. 2020. View Article : Google Scholar : PubMed/NCBI

13 

Wang Y, Deng P, Liu Y, Wu Y, Chen Y, Guo Y, Zhang S, Zheng X, Zhou L, Liu W, et al: Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nat Commun. 11:55962020. View Article : Google Scholar : PubMed/NCBI

14 

Gyanwali B, Lim ZX, Soh J, Lim C, Guan SP, Goh J, Maier AB and Kennedy BK: Alpha-Ketoglutarate dietary supplementation to improve health in humans. Trends Endocrinol Metab. 33:136–146. 2022. View Article : Google Scholar : PubMed/NCBI

15 

Yamamoto T, Sato K, Yamaguchi M, Mitamura K and Taga A: Development of simultaneous quantitative analysis of tricarboxylic acid cycle metabolites to identify specific metabolites in cancer cells by targeted metabolomic approach. Biochem Biophys Res Commun. 584:53–59. 2021. View Article : Google Scholar : PubMed/NCBI

16 

Woyke S, Mair N, Ortner A, Haller T, Ronzani M, Rugg C, Ströhle M, Wintersteiger R and Gatterer H: Dose- and sex-dependent changes in hemoglobin oxygen affinity by the micronutrient 5-hydroxymethylfurfural and α-ketoglutaric acid. Nutrients. 13:34482021. View Article : Google Scholar : PubMed/NCBI

17 

Niebisch A, Kabus A, Schultz C, Weil B and Bott M: Corynebacterial protein kinase G controls 2-oxoglutarate dehydrogenase activity via the phosphorylation status of the OdhI protein. J Biol Chem. 281:12300–12307. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Krawczyk S, Raasch K, Schultz C, Hoffelder M, Eggeling L and Bott M: The FHA domain of OdhI interacts with the carboxyterminal 2-oxoglutarate dehydrogenase domain of OdhA in Corynebacterium glutamicum. FEBS Lett. 584:1463–1468. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Lockwood LB and Stodola FH: Preliminary studies on the production of alpha-ketoglutaric acid by Pseudomonas fluorescens. J Biol Chem. 164:81–83. 1946. View Article : Google Scholar : PubMed/NCBI

20 

Otto C, Yovkova V and Barth G: Overproduction and secretion of alpha-ketoglutaric acid by microorganisms. Appl Microbiol Biotechnol. 92:689–695. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Guo H, Su S, Madzak C, Zhou J, Chen H and Chen G: Applying pathway engineering to enhance production of alpha-ketoglutarate in Yarrowia lipolytica. Appl Microbiol Biotechnol. 100:9875–9884. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Guo H, Du G, Zhou J and Chen J: Progress in microbial production of alpha-ketoglutarate. Sheng Wu Gong Cheng Xue Bao. 29:141–152. 2013.(In Chinese). PubMed/NCBI

23 

Bartlett DE, Miller RB, Thiesfeldt S, Lakhani HV, Shapiro JI and Sodhi K: The role of Na/K-ATPase signaling in oxidative stress related to aging: Implications in obesity and cardiovascular disease. Int J Mol Sci. 19:21392018. View Article : Google Scholar : PubMed/NCBI

24 

Liang WD, Huang PJ, Xiong LH, Zhou S, Ye RY, Liu JR, Wei H and Lai RY: Metabolomics and its application in the mechanism analysis on diabetic bone metabolic abnormality. Eur Rev Med Pharmacol Sci. 24:9591–9600. 2020.PubMed/NCBI

25 

Cheng MX, Cao D, Chen Y, Li JZ, Tu B and Gong JP: α-ketoglutarate attenuates ischemia-reperfusion injury of liver graft in rats. Biomed Pharmacother. 111:1141–1146. 2019. View Article : Google Scholar : PubMed/NCBI

26 

Olenchock BA, Moslehi J, Baik AH, Davidson SM, Williams J, Gibson WJ, Chakraborty AA, Pierce KA, Miller CM, Hanse EA, et al: EGLN1 inhibition and rerouting of alpha-ketoglutarate suffice for remote ischemic protection. Cell. 165:4972016. View Article : Google Scholar : PubMed/NCBI

27 

O'Rourke MF and Hashimoto J: Mechanical factors in arterial aging: A clinical perspective. J Am Coll Cardiol. 50:1–13. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Satpute RM, Hariharakrishnan J and Bhattacharya R: Effect of alpha-ketoglutarate and N-acetyl cysteine on cyanide-induced oxidative stress mediated cell death in PC12 cells. Toxicol Ind Health. 26:297–308. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Chen P, Hou L, Luo Y, Chen L, Li S, Lei X, Huang J and Wu D: Effect of diabetes on the assessment role of 2-oxoglutarate to the severity of chronic heart failure. Exp Clin Endocrinol Diabetes. 126:478–486. 2018. View Article : Google Scholar : PubMed/NCBI

30 

An D, Zeng Q, Zhang P, Ma Z, Zhang H, Liu Z, Li J, Ren H and Xu D: Alpha-ketoglutarate ameliorates pressure overload-induced chronic cardiac dysfunction in mice. Redox Biol. 46:1020882021. View Article : Google Scholar : PubMed/NCBI

31 

Greilberger J, Herwig R, Greilberger M, Stiegler P and Wintersteiger R: Alpha-Ketoglutarate and 5-HMF: A potential anti-tumoral combination against leukemia cells. Antioxidants (Basel). 10:18042021. View Article : Google Scholar : PubMed/NCBI

32 

Mendoza G and Merchant H: Motor system evolution and the emergence of high cognitive functions. Prog Neurobiol. 122:73–93. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Cai X, Yuan Y, Liao Z, Xing K, Zhu C, Xu Y, Yu L, Wang L, Wang S, Zhu X, et al: alpha-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway. FASEB J. 32:488–499. 2018. View Article : Google Scholar : PubMed/NCBI

34 

Ge J, Cui H, Xie N, Banerjee S, Guo S, Dubey S, Barnes S and Liu G: Glutaminolysis promotes collagen translation and stability via alpha-ketoglutarate-mediated mTOR activation and proline hydroxylation. Am J Respir Cell Mol Biol. 58:378–390. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Xiong G, Stewart RL, Chen J, Gao T, Scott TL, Samayoa LM, O'Connor K, Lane AN and Xu R: Collagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance. Nat Commun. 9:44562018. View Article : Google Scholar : PubMed/NCBI

36 

Zurek A, Mizerska-Kowalska M, Slawinska-Brych A, Kaławaj K, Bojarska-Junak A, Kandefer-Szerszeń M and Zdzisińska B: Alpha ketoglutarate exerts a pro-osteogenic effect in osteoblast cell lines through activation of JNK and mTOR/S6K1/S6 signaling pathways. Toxicol Appl Pharmacol. 374:53–64. 2019. View Article : Google Scholar : PubMed/NCBI

37 

Filip RS, Pierzynowski SG, Lindegard B, Wernerman J, Haratym-Maj A and Podgurniak M: Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: Six-month study. Int J Vitam Nutr Res. 77:89–97. 2007. View Article : Google Scholar : PubMed/NCBI

38 

Sliwa E, Tatara MR, Nowakowski H, Pierzynowski SG and Studzinski T: Effect of maternal dexamethasone and alpha-ketoglutarate administration on skeletal development during the last three weeks of prenatal life in pigs. J Matern Fetal Neonatal Med. 19:489–493. 2006. View Article : Google Scholar : PubMed/NCBI

39 

Hammarqvist F, Wernerman J, von der Decken A and Vinnars E: Alpha-ketoglutarate preserves protein synthesis and free glutamine in skeletal muscle after surgery. Surgery. 109:28–36. 1991.PubMed/NCBI

40 

Radzki RP, Bienko M and Pierzynowski SG: Anti-osteopenic effect of alpha-ketoglutarate sodium salt in ovariectomized rats. J Bone Miner Metab. 30:651–659. 2012. View Article : Google Scholar : PubMed/NCBI

41 

Godsora BKJ, Prakash P, Punekar NS and Bhaumik P: Molecular insights into the inhibition of glutamate dehydrogenase by the dicarboxylic acid metabolites. Proteins. 90:810–823. 2022. View Article : Google Scholar : PubMed/NCBI

42 

Alrefai H, Allababidi H, Levy S and Levy J: The endocrine system in diabetes mellitus. Endocrine. 18:105–119. 2002. View Article : Google Scholar : PubMed/NCBI

43 

Temneanu OR, Trandafir LM and Purcarea MR: Type 2 diabetes mellitus in children and adolescents: A relatively new clinical problem within pediatric practice. J Med Life. 9:235–239. 2016.PubMed/NCBI

44 

Rabaglia ME, Gray-Keller MP, Frey BL, Shortreed MR, Smith LM and Attie AD: Alpha-Ketoisocaproate-induced hypersecretion of insulin by islets from diabetes-susceptible mice. Am J Physiol Endocrinol Metab. 289:E218–E224. 2005. View Article : Google Scholar : PubMed/NCBI

45 

Macdonald MJ: Export of metabolites from pancreatic islet mitochondria as a means to study anaplerosis in insulin secretion. Metabolism. 52:993–998. 2003. View Article : Google Scholar : PubMed/NCBI

46 

Odegaard ML, Joseph JW, Jensen MV, Lu D, Ilkayeva O, Ronnebaum SM, Becker TC and Newgard CB: The mitochondrial 2-oxoglutarate carrier is part of a metabolic pathway that mediates glucose- and glutamine-stimulated insulin secretion. J Biol Chem. 285:16530–16537. 2010. View Article : Google Scholar : PubMed/NCBI

47 

Fahien LA, MacDonald MJ, Kmiotek EH, Mertz RJ and Fahien CM: Regulation of insulin release by factors that also modify glutamate dehydrogenase. J Biol Chem. 263:13610–13614. 1988. View Article : Google Scholar : PubMed/NCBI

48 

Tan Q, Wang W, Yang C, Zhang J, Sun K, Luo HC, Mai LF, Lao Y, Yan L and Ren M: α-ketoglutarate is associated with delayed wound healing in diabetes. Clin Endocrinol (Oxf). 85:54–61. 2016. View Article : Google Scholar : PubMed/NCBI

49 

Ren W, Xia Y, Chen S, Wu G, Bazer FW, Zhou B, Tan B, Zhu G, Deng J and Yin Y: Glutamine metabolism in macrophages: A novel target for obesity/type 2 diabetes. Adv Nutr. 10:321–330. 2019. View Article : Google Scholar : PubMed/NCBI

50 

Poddar M, Chetty Y and Chetty VT: How does obesity affect the endocrine system? A narrative review. Clin Obes. 7:136–144. 2017. View Article : Google Scholar : PubMed/NCBI

51 

Kang HS, Lee JH, Oh KJ, Lee EW, Han BS, Park KY, Suh JM, Min JK, Chi SW, Lee SC, et al: IDH1-dependent alpha-KG regulates brown fat differentiation and function by modulating histone methylation. Metabolism. 105:1541732020. View Article : Google Scholar : PubMed/NCBI

52 

Wu L, Xia M, Duan Y, Zhang L, Jiang H, Hu X, Yan H, Zhang Y, Gu Y, Shi H, et al: Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans. Cell Death Dis. 10:4682019. View Article : Google Scholar : PubMed/NCBI

53 

Yang Q, Liang X, Sun X, Zhang L, Fu X, Rogers CJ, Berim A, Zhang S, Wang S, Wang B, et al: AMPK/α-ketoglutarate axis dynamically mediates DNA demethylation in the Prdm16 promoter and brown adipogenesis. Cell Metab. 24:542–554. 2016. View Article : Google Scholar : PubMed/NCBI

54 

Liu Z, Gan L, Zhang T, Ren Q and Sun C: Melatonin alleviates adipose inflammation through elevating α-ketoglutarate and diverting adipose-derived exosomes to macrophages in mice. J Pineal Res. 64:2018. View Article : Google Scholar

55 

Shamburek RD and Farrar JT: Disorders of the digestive system in the elderly. N Engl J Med. 322:438–443. 1990. View Article : Google Scholar : PubMed/NCBI

56 

Geboes K, Geboes KP and Maleux G: Vascular anatomy of the gastrointestinal tract. Best Pract Res Clin Gastroenterol. 15:1–14. 2001. View Article : Google Scholar : PubMed/NCBI

57 

Hur H, Paik MJ, Xuan Y, Nguyen DT, Ham IH, Yun J, Cho YK, Lee G and Han SU: Quantitative measurement of organic acids in tissues from gastric cancer patients indicates increased glucose metabolism in gastric cancer. PLoS One. 9:e985812014. View Article : Google Scholar : PubMed/NCBI

58 

Kim KB, Yang JY, Kwack SJ, Park KL, Kim HS, Ryu DH, Kim YJ, Hwang GS and Lee BM: Toxicometabolomics of urinary biomarkers for human gastric cancer in a mouse model. J Toxicol Environ Health A. 73:1420–1430. 2010. View Article : Google Scholar : PubMed/NCBI

59 

Cui P, Huang C, Guo J, Wang Q, Liu Z, Zhuo H and Lin D: Metabolic profiling of tumors, sera, and skeletal muscles from an orthotopic murine model of gastric cancer associated-cachexia. J Proteome Res. 18:1880–1892. 2019. View Article : Google Scholar : PubMed/NCBI

60 

Tomaszewska E, Dobrowolski P and Puzio I: Postnatal administration of 2-oxoglutaric acid improves the intestinal barrier affected by the prenatal action of dexamethasone in pigs. Nutrition. 28:190–196. 2012. View Article : Google Scholar : PubMed/NCBI

61 

He L, Huang N, Li H, Tian J, Zhou X, Li T, Yao K, Wu G and Yin Y: AMPK/α-ketoglutarate axis regulates intestinal water and ion homeostasis in young pigs. J Agric Food Chem. 65:2287–2298. 2017. View Article : Google Scholar : PubMed/NCBI

62 

Junghans P, Derno M, Pierzynowski S, Hennig U, Eberhard Rudolph P and Souffrant WB: Intraduodenal infusion of alpha-ketoglutarate decreases whole body energy expenditure in growing pigs. Clin Nutr. 25:489–496. 2006. View Article : Google Scholar : PubMed/NCBI

63 

Hou Y, Yao K, Wang L, Ding B, Fu D, Liu Y, Zhu H, Liu J, Li Y, Kang P, et al: Effects of α-ketoglutarate on energy status in the intestinal mucosa of weaned piglets chronically challenged with lipopolysaccharide. Br J Nutr. 106:357–363. 2011. View Article : Google Scholar : PubMed/NCBI

64 

He L, Wu J, Tang W, Zhou X, Lin Q, Luo F, Yin Y and Li T: Prevention of oxidative stress by alpha-ketoglutarate via activation of CAR signaling and modulation of the expression of key antioxidant-associated targets in vivo and in vitro. J Agric Food Chem. 66:11273–11283. 2018. View Article : Google Scholar : PubMed/NCBI

65 

Zhang Z, He C, Zhang L, Zhu T, Lv D, Li G, Song Y, Wang J, Wu H, Ji P and Liu G: Alpha-ketoglutarate affects murine embryo development through metabolic and epigenetic modulations. Reproduction. 158:123–133. 2019. View Article : Google Scholar : PubMed/NCBI

66 

Zhang Z, He C, Gao Y, Zhang L, Song Y, Zhu T, Zhu K, Lv D, Wang J, Tian X, et al: α-ketoglutarate delays age-related fertility decline in mammals. Aging Cell. 20:e132912021. View Article : Google Scholar : PubMed/NCBI

67 

Tanaka K, Hayashi Y, Takehara A, Ito-Matsuoka Y, Tachibana M, Yaegashi N and Matsui Y: Abnormal early folliculogenesis due to impeded pyruvate metabolism in mouse oocytesdagger. Biol Reprod. 105:64–75. 2021. View Article : Google Scholar : PubMed/NCBI

68 

Teng X, Emmett MJ, Lazar MA, Goldberg E and Rabinowitz JD: Lactate dehydrogenase C produces S-2-hydroxyglutarate in mouse testis. ACS Chem Biol. 11:2420–2427. 2016. View Article : Google Scholar : PubMed/NCBI

69 

Plaitakis A, Kalef-Ezra E, Kotzamani D, Zaganas I and Spanaki C: The glutamate dehydrogenase pathway and its roles in cell and tissue biology in health and disease. Biology (Basel). 6:112017.PubMed/NCBI

70 

Li SF, Liu HX, Zhang YB, Yan YC and Li YP: The protective effects of alpha-ketoacids against oxidative stress on rat spermatozoa in vitro. Asian J Androl. 12:247–256. 2010. View Article : Google Scholar : PubMed/NCBI

71 

Kalawaj K, Slawinska-Brych A, Mizerska-Kowalska M, Żurek A, Bojarska-Junak A, Kandefer-Szerszeń M and Zdzisińska B: Alpha ketoglutarate exerts in vitro anti-osteosarcoma effects through inhibition of cell proliferation, induction of apoptosis via the JNK and caspase 9-dependent mechanism, and suppression of TGF-β and VEGF production and metastatic potential of cells. Int J Mol Sci. 21:94062020. View Article : Google Scholar : PubMed/NCBI

72 

Demidenko O, Barardo D, Budovskii V, Finnemore R, Palmer FR, Kennedy BK and Budovskaya YV: Rejuvant(R), a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging (Albany NY). 13:24485–24499. 2021. View Article : Google Scholar : PubMed/NCBI

73 

Gou L, Lee J, Yang JM, Park YD, Zhou HM, Zhan Y and Lü ZR: The effect of alpha-ketoglutaric acid on tyrosinase activity and conformation: Kinetics and molecular dynamics simulation study. Int J Biol Macromol. 105:1654–1662. 2017. View Article : Google Scholar : PubMed/NCBI

74 

Bayliak MM, Hrynkiv OV, Knyhynytska RV and Lushchak VI: Alpha-ketoglutarate enhances freeze-thaw tolerance and prevents carbohydrate-induced cell death of the yeast Saccharomyces cerevisiae. Arch Microbiol. 200:33–46. 2018. View Article : Google Scholar : PubMed/NCBI

75 

Chen J, Zhang H, Gao H, Kang B, Chen F, Li Y, Fu C and Yao K: Effects of dietary supplementation of alpha-ketoglutarate in a low-protein diet on fatty acid composition and lipid metabolism related gene expression in muscles of growing pigs. Animals (Basel). 9:8382019. View Article : Google Scholar : PubMed/NCBI

76 

Bayliak MM and Lushchak VI: Pleiotropic effects of alpha-ketoglutarate as a potential anti-ageing agent. Ageing Res Rev. 66:1012372021. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Meng X, Liu H, Peng L, He W and Li S: Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review). Mol Med Rep 25: 151, 2022.
APA
Meng, X., Liu, H., Peng, L., He, W., & Li, S. (2022). Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review). Molecular Medicine Reports, 25, 151. https://doi.org/10.3892/mmr.2022.12667
MLA
Meng, X., Liu, H., Peng, L., He, W., Li, S."Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review)". Molecular Medicine Reports 25.5 (2022): 151.
Chicago
Meng, X., Liu, H., Peng, L., He, W., Li, S."Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review)". Molecular Medicine Reports 25, no. 5 (2022): 151. https://doi.org/10.3892/mmr.2022.12667
Copy and paste a formatted citation
x
Spandidos Publications style
Meng X, Liu H, Peng L, He W and Li S: Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review). Mol Med Rep 25: 151, 2022.
APA
Meng, X., Liu, H., Peng, L., He, W., & Li, S. (2022). Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review). Molecular Medicine Reports, 25, 151. https://doi.org/10.3892/mmr.2022.12667
MLA
Meng, X., Liu, H., Peng, L., He, W., Li, S."Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review)". Molecular Medicine Reports 25.5 (2022): 151.
Chicago
Meng, X., Liu, H., Peng, L., He, W., Li, S."Potential clinical applications of alpha‑ketoglutaric acid in diseases (Review)". Molecular Medicine Reports 25, no. 5 (2022): 151. https://doi.org/10.3892/mmr.2022.12667
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team