The data demonstrate that iPGAMs and glycolytic activity are critical for guard cell function and fertility in Arabidopsis. Comparative proteome analysis of human lung squamous cell carcinoma. eCollection 2020. However, the Warburg effect highlights that cancer cells mainly produce energy via glycolysis, even in an aerobic environment.38 Therefore, to provide sufficient ATP and carbon for the necessary building blocks of the cellular processes such as nucleotides, amino acids, lipids and NADPH, cancer cells require a higher glucose intake than normal cells to meet the energy requirements for rapid proliferation.38–40 Subsequently, this overactive glycolysis may play a role in promoting tumor cell proliferation.41. In this review, we summarized the current knowledge of the role of PGAM1 and its inhibitors in the regulation of tumor malignant behaviors, as well as current developments on target drugs for PGAM1. Huang K, Jiang L, Li H, Ye D, Zhou L. Development of anthraquinone analogues as phosphoglycerate mutase 1 inhibitors. 1956;124(3215):270–272. Finally, the correlation between PGAM1 and cancer prognosis has been gaining attention and further research will identify whether PGAM1 can be used as a biomarker for early cancer detection. 2011;43(9):869–874. Cancer Cell. It is a tetronic acid derivative and a monophosphoglyceric acid. Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Plant Cell Physiol. 2011 Aug;156(4):1740-53. doi: 10.1104/pp.111.174466. Li C, Shu F, Lei B, Lv D, Zhang S, Mao X. Dev Biol. Phosphoglycerate Mutase and Bisphosphoglycerate Synthase” ... phoryl enzyme functions in the direct path of catalysis. 2,3-biphosphoglycerate-independent phosphoglycerate mutase (iPGAM) is a key enzymatic activity in glycolysis and catalyses the reversible interconversion of 3-phosphoglycerate to 2-phosphoglycerate. It is an intermediate in metabolic pathways like glycolysis and calvin cycle. doi:10.1038/nrc2676, 48. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. The pharmacological inhibitors are small molecular compounds, with six types of small molecules reported to inhibit PGAM1, and which are mainly associated with metabolism and cancer cell proliferation. In addition to the proliferation of tumor cells, tumor metastasis is also an important factor affecting the prognosis of cancer patients. However, most of the PGAM1 inhibitors were glycolysis-targeted with minimal to no effect on the invasion and metastasis of cancer cells (Table 1). Epub 2013 Oct 7. doi:10.1039/b705113a, 22. Increasing evidence has indicated the vital biological roles of PGAM1 in tumor progression. Vander Heiden MG, Cantley LC, Thompson CB. •  Testimonials   doi:10.1073/pnas.94.13.6658, 5. 2,3-biphosphoglycerate-independent phosphoglycerate mutase (iPGAM) is a key enzymatic activity in glycolysis and catalyses the reversible interconversion of 3-phosphoglycerate to 2-phosphoglycerate. 229, 383-7, (1988). DM et al.46 reported PGAM1 was overexpressed in the cytoplasm of capillary/artery endothelial cells, suggesting a potential correlation between PGAM1 and tumor invasion and metastasis. 35. By accessing the work you hereby accept the Terms. This site needs JavaScript to work properly. •  software development by maffey.com USA.gov. doi:10.1016/j.cell.2008.11.044. Phosphoglycerate mutase is involved in a critical energy-producing process known as glycolysis. Phosphoglycerate kinase is a crucial enzyme in the glycolysis cycle. Huang et al.51 revealed that F22, K100, and R116 of PGAM1 residues were critical for the binding of inhibitors and that compound 9i, an anthraquinone inhibitor, significantly decreased lung cancer cell proliferation in different cell lines, which is a promising inhibitor for PGAM1. Phosphoglycerate mutase 2 , Phosphoglycerate mutase 1 , Phosphoglycerate mutase 3 (GPM3) Enolase 2 ( ENO2 ) , Enolase-related protein 2 ( ERR2 ) , Enolase-related protein 1 ( ERR1 ) , Enolase-related protein 3 ( ERR3 ) , Enolase 1 ( ENO1 ) Every step is catalyzed by one or more enzymes that enhance the rate of the given reaction. Science. 57. 2000;82(1):20–27. 2016;132:85–92. Extracellular nucleotides and apyrases regulate stomatal aperture in Arabidopsis. Recently, Zhang et al.23 confirmed that PGAM1 can promote tumor metastasis through a non-metabolic function. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Inhibition of lactate dehydrogenase a induces oxidative stress and inhibits tumor progression. Oncogene. This site is owned and operated by Informa PLC ( “Informa”) whose registered office is 5 Howick Place, London SW1P 1WG. • Web Design by Adhesion. Nucleic Acids Res. A possible role for glycolysis in contributing to the energetic, reducing requirements, or signalling processes regulating stomatal movements has not been investigated previously. Here we report the interaction of Pak with phosphoglycerate mutase (PGAM)-B, an enzyme of the glycolytic pathway. Glycolysis, oxidization of glucose to pyruvate, is a central metabolic pathway and yields a net gain of 2 ATP and 2 NADH. doi:10.1016/j.cmet.2019.09.014. 2008;32(10):1215–1222. Dove Medical Press is a member of the OAI. Mutase Structure The secondary structure of PGM is categorised as an alpha/beta protein, which has three alpha, beta, alpha layers. Copyright 2017 Informa PLC. To investigate functions of iPGAMs and glycolysis in stomatal function and plant growth, Arabidopsis insertional mutants in At1g09780 and At3g08590, both of which have been annotated as iPGAMs on the basis of sequence homology, were identified and characterized. However, it remains unclear whether PGAM1 can promote cancer malignant behaviors through a non-metabolic pathway. The alternative recombinant metabolic pattern of cancer cells was considered to provide new opportunities for cancer treatment, which lead researchers to investigate the roles of metabolic enzymes during the development of cancer.42,43 Therefore, the relationship between the metabolic changes brought by PGAM1 and cancer are gradually being explored. 2000;28: 235-242.59, The primary role of PGAM1 is to catalyze the reversible conversion of 3-PG to 2-PG,11 a critical step in glycolysis (Figure 2). 1997;94(13):6658–6663. Bisphosphoglycerate mutase (BPGM) is an enzyme unique to erythrocytes and placental cells. Nucleic Acids Res. New Phytologist. According to a study by Liu et al,36 PGAM1 is a downstream target of the PI3K/Akt/mTOR/HIF-1α pathway, which regulates cellular metabolism (Figure 2). -, Andriotis VM, Kruger NJ, Pike MJ, Smith AM. Immunohistochemical localization of Phosphoglycerate mutase in capillary endothelium of the brain and periphery. Bulk reprints for the pharmaceutical industry. 2020 Jun 29;8:e9107. Many studies have highlighted the metabolic role of PGAM1 in promoting cancer cell proliferation. 1956;123(3191):309–314. J Exp Med. doi:10.1084/jem.20120162, 43. This work is published and licensed by Dove Medical Press Limited. open access to scientific and medical research. Ren F, Wu H, Lei Y, et al. doi:10.1054/bjoc.1999.0871, 26. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes in breast carcinoma. Subsequently, a significant decrease in the pentose phosphate pathway (PPP) flux and biosynthesis as well as an attenuated cell proliferation and tumor growth were observed in the breast cancer cell line MDA-MB-231, the lung cancer cell line H1299, the acute myeloid leukemia cell line Molm14, and in the head and neck cancer cell line 212LN. Mol Cancer. Alexa A, Rahnenfuhrer J, Lengauer T. Improved scoring of functional groups from gene expression data by decorrelating GO graph structure. Warburg O. Phosphoglycerate kinase is the seventh enzyme in the cycle which catalyzes the reaction of 1,3-Biphosphoglycerate and ADP to produce 3-Phosphoglycerate and ATP. doi:10.1159/000245893. However, the relationship between the metabolic role of PGAM1 and tumor metastasis has been infrequently reported. Epub 2013 Aug 30. 2000;28:235–242. Cofactor-dependent phosphoglycerate mutase exists as a homodimer composed of alpha/beta subunits with a t wo-fold symmetry about the central core. PGAM1 was also suggested to be an independent risk factor for OS and DFS. Nat Commun. Open access peer-reviewed scientific and medical journals. The diagnostic value and functional roles of phosphoglycerate mutase 1 in glioma. 2010;329(5998):1492–1499. Activated Pak1 inhibits glycolysis by association of its catalytic domain with PGAM-B and subsequent phosphorylation of the enzyme on serine … Influence of salt, substrate, and cofactor concentrations on the kinetic and mechanistic behavior of phosphoglycerate mutase. doi:10.1038/s41418-017-0034-y, 16. 2015 Jun;56(6):1239-48. doi: 10.1093/pcp/pcv051. UK VAT Group: GB 365 4626 36. Oncol Rep. 2016;36(4):2236–2244. Hitosugi T, Zhou L, Elf S, et al. 2007;3(7):495–506. Fothergill-Gilmore LA, Watson HC. Durany N, Joseph J, Jimenez OM, et al. Similarly, in the yeast Candida albicans , phosphoglycerate mutase (Gpmlp) can localize to the cell wall, where it can facilitate binding to host proteins, possibly as a mechanism of immune evasion during infection [ 28 ]. Phosphoglycerate mutase produces reversible reactions. Phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by critically catalyzing the conversion of 3-phosphoglycerate (3-PG) to 2- phosphoglycerate (2-PG) during aerobic glycolysis, which regu- latesintermediatesusedasprecursorsforanabolicbiosynthesis Context and Significance Phosphoglycerate mutase 1 (PGAM1) is involved in promoting tumor progression in several cancers … 1999;289(4):691–699. 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