A New View into the Regulation of Purine Metabolism: The Purinosome

Trends in Biochemical Sciences

Volumn 42, Issue 2, 2017, Pages 141-154

  Pedley, Anthony M ^a   Benkovic, Stephen J ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

metabolon; purine metabolism; purinosome

Indexed keywords

6 MERCAPTOPURINE DERIVATIVE; ANTINEOPLASTIC ANTIMETABOLITE; DEOXYPURINE DERIVATIVE; LOMETREXOL; MAMMALIAN TARGET OF RAPAMYCIN; MERCAPTOPURINE; METHOTREXATE; MULTIENZYME COMPLEX; PEMETREXED; PURINE; PURINOSOME; UNCLASSIFIED DRUG; PURINE DERIVATIVE;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; CANCER THERAPY; CELL METABOLISM; CELLULAR DISTRIBUTION; DRUG MECHANISM; DRUG TARGETING; ENZYME ACTIVITY; ENZYME LOCALIZATION; ENZYME METABOLISM; HUMAN; METABOLIC REGULATION; MITOCHONDRION; MOLECULARLY TARGETED THERAPY; NONHUMAN; PROTEIN ANALYSIS; PROTEIN ASSEMBLY; PROTEIN FUNCTION; PURINE METABOLISM; PURINE SYNTHESIS; REVIEW; METABOLISM; MICROTUBULE; NEOPLASM;

HUMANS; MICROTUBULES; MITOCHONDRIA; NEOPLASMS; PURINES;

EID: 85005975973     PISSN: 09680004     EISSN: 13624326     Source Type: Journal    
DOI: 10.1016/j.tibs.2016.09.009     Document Type: Review

References (88)

1. 1 Buchanan, J.M., Hartman, S.C., Enzymic reactions in the synthesis of the purines. Ford, F.F., (eds.) Advances in Enzymology and Related Areas of Molecular Biology, 1959, John Wiley & Sons, 199–261.
2. 2 Greenberg, G.R., Jaenicke, L., On the activation of the one-carbon unit for the biosynthesis of purine nucleotides. Wolstenholme, G.E.W., O'Connor, C.M., (eds.) Ciba Foundation Symposium - Chemistry and Biology of Purines, 1957, John Wiley & Sons, 204–232.
3. 3 Hartman, S.C., Buchanan, J.M., Nucleic acids, purines, pyrimidines (nucleotide synthesis). Annu. Rev. Biochem. 28 (1959), 365–410.
4. 4 Rudolph, J., Stubbe, J., Investigation of the mechanism of phosphoribosylamine transfer from glutamine phosphoribosylpyrophosphate amidotransferase to glycinamide ribonucleotide synthetase. Biochemistry 34 (1995), 2241–2250.
5. 5 Smith, G.K., et al. Characterization of the enzyme complex involving the folate-requiring enzymes of de novo purine biosynthesis. Biochemistry 19 (1980), 4313–4321.
6. 6 An, S., et al. Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science 320 (2008), 103–106.
7. 7 Henderson, J.F., Khoo, K.Y., On the mechanism of feedback inhibition of purine biosynthesis de novo in Ehrlich ascites tumor cells in vitro. J. Biol. Chem. 240 (1965), 3104–3109.
8. 8 Murray, A.W., The biological significance of purine salvage. Annu. Rev. Biochem. 40 (1971), 811–826.
9. 9 Yamaoka, T., et al. Amidophosphoribosyltransferase limits the rate of cell growth-linked de novo purine biosynthesis in the presence of constant capacity of salvage purine biosynthesis. J. Biol. Chem. 272 (1997), 17719–17725.
10. 10 Mayer, D., et al. Expression of key enzymes of purine and pyrimidine metabolism in a hepatocyte-derived cell line at different phases of the growth cycle. J. Cancer Res. Clin. Oncol. 116 (1990), 251–258.
11. 11 Natsumeda, Y., et al. Enzymic capacities of purine de novo and salvage pathways for nucleotide synthesis in normal and neoplastic tissues. Cancer Res. 44 (1984), 2475–2479.
12. 12 Fan, J., et al. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 510 (2014), 298–302.
13. 13 Ducker, G.S., et al. Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway. Cell Metab. 23 (2016), 1140–1153.
14. 14 Ahn, C.S., Metallo, C.M., Mitochondria as biosynthetic factories for cancer proliferation. Cancer Metab., 3, 2015, 1.
15. 15 Lewis, C.A., et al. Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol. Cell 55 (2014), 253–263.
16. 16 Greasley, S.E., et al. Crystal structure of a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis. Nat. Struct. Biol. 8 (2001), 402–406.
17. 17 Vergis, J.M., et al. Human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine 5’-monophosphate cyclohydrolase. A bifunctional protein requiring dimerization for transformylase activity but not for cyclohydrolase activity. J. Biol. Chem. 276 (2001), 7727–7733.
18. 18 Holmes, E.W., et al. Human glutamine phosphoribosylpyrophosphate amidotransferase. Kinetic and regulatory properties. J. Biol. Chem. 248 (1973), 144–150.
19. 19 Smith, J.L., Glutamine PRPP amidotransferase: snapshots of an enzyme in action. Curr. Opin. Struct. Biol. 8 (1998), 686–694.
20. 20 Yamaoka, T., et al. Feedback inhibition of amidophosphoribosyltransferase regulates the rate of cell growth via purine nucleotide, DNA, and protein syntheses. J. Biol. Chem. 276 (2001), 21285–21291.
21. 21 Zhou, G., et al. Binding of purine nucleotides to two regulatory sites results in synergistic feedback inhibition of glutamine 5-phosphoribosylpyrophosphate amidotransferase. J. Biol. Chem. 269 (1994), 6784–6789.
22. 22 Asby, D.J., et al. AMPK Activation via modulation of de novo purine biosynthesis with an inhibitor of ATIC homodimerization. Chem. Biol. 22 (2015), 838–848.
23. 23 Liu, X., et al. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proc. Natl. Acad. Sci. U.S.A. 111 (2014), E435–E444.
24. 24 Schmitt, D.L., et al. Sequestration-mediated downregulation of de novo purine biosynthesis by AMPK. ACS Chem. Biol. 11 (2016), 1917–1924.
25. 25 Keller, K.E., et al. SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells. Mol. Cell 53 (2014), 700–709.
26. 26 Keller, K.E., et al. SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions. Science 338 (2012), 1069–1072.
27. 27 Yan, M., et al. Succinyl-5-aminoimidazole-4-carboxamide-1-ribose 5’-phosphate (SAICAR) activates pyruvate kinase isoform M2 (PKM2) in its dimeric form. Biochemistry 55 (2016), 4731–4736.
28. 28 Barnes, S.J., Weitzman, P.D., Organization of citric acid cycle enzymes into a multienzyme cluster. FEBS Lett. 201 (1986), 267–270.
29. 29 Campanella, M.E., et al. Assembly and regulation of a glycolytic enzyme complex on the human erythrocyte membrane. Proc. Natl. Acad. Sci. U.S.A. 102 (2005), 2402–2407.
30. 30 Schendel, F.J., et al. Characterization and chemical properties of phosphoribosylamine, an unstable intermediate in the de novo purine biosynthetic pathway. Biochemistry 27 (1988), 2614–2623.
31. 31 Antle, V.D., et al. Substrate specificity of glycinamide ribonucleotide synthetase from chicken liver. J. Biol. Chem. 271 (1996), 8192–8195.
32. 32 Zhang, Q.C., et al. Structure-based prediction of protein-protein interactions on a genome-wide scale. Nature 490 (2012), 556–560.
33. 33 Baresova, V., et al. CRISPR–Cas9 induced mutations along de novo purine synthesis in HeLa cells result in accumulation of individual enzyme substrates and affect purinosome formation. Mol. Genet. Metab., 2016, 10.1016/j.ymgme.2016.08.004 Published online August 24, 2016.
34. 34 Baresova, V., et al. Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency. Hum. Mol. Genet. 21 (2012), 1534–1543.
35. 35 Zhao, H., et al. Quantitative analysis of purine nucleotides indicates that purinosomes increase de novo purine biosynthesis. J. Biol. Chem. 290 (2015), 6705–6713.
36. 36 Chan, C.Y., et al. Purinosome formation as a function of the cell cycle. Proc. Natl. Acad. Sci. U.S.A. 112 (2015), 1368–1373.
37. 37 French, J.B., et al. Hsp70/Hsp90 chaperone machinery is involved in the assembly of the purinosome. Proc. Natl. Acad. Sci. U.S.A. 110 (2013), 2528–2533.
38. 38 Deng, Y., et al. Mapping protein-protein proximity in the purinosome. J. Biol. Chem. 287 (2012), 36201–36207.
39. 39 Havugimana, P.C., et al. A census of human soluble protein complexes. Cell 150 (2012), 1068–1081.
40. 40 Kristensen, A.R., et al. A high-throughput approach for measuring temporal changes in the interactome. Nat. Methods 9 (2012), 907–909.
41. 41 Wan, C., et al. Panorama of ancient metazoan macromolecular complexes. Nature 525 (2015), 339–344.
42. 42 Kyoung, M., et al. Dynamic architecture of the purinosome involved in human de novo purine biosynthesis. Biochemistry 54 (2015), 870–880.
43. 43 Fridman, A., et al. Cell cycle regulation of purine synthesis by phosphoribosyl pyrophosphate and inorganic phosphate. Biochem. J. 454 (2013), 91–99.
44. 44 Allen, J.J., Development and Application of Technologies to Study Individual Kinase Substrate Relationships. In Chemistry and Chemical Biology. 2008, University of California, San Francisco.
45. 45 Salvi, M., et al. Extraordinary pleiotropy of protein kinase CK2 revealed by weblogo phosphoproteome analysis. Biochim. Biophys. Acta 1793 (2009), 847–859.
46. 46 Venerando, A., et al. Casein kinase: the triple meaning of a misnomer. Biochem. J. 460 (2014), 141–156.
47. 47 An, S., et al. Dynamic regulation of a metabolic multi-enzyme complex by protein kinase CK2. J. Biol. Chem. 285 (2010), 11093–11099.
48. 48 Duncan, J.S., et al. An unbiased evaluation of CK2 inhibitors by chemoproteomics: characterization of inhibitor effects on CK2 and identification of novel inhibitor targets. Mol. Cell. Proteomics 7 (2008), 1077–1088.
49. 49 Pagano, M.A., et al. The selectivity of inhibitors of protein kinase CK2: an update. Biochem. J. 415 (2008), 353–365.
50. 50 Verrier, F., et al. GPCRs regulate the assembly of a multienzyme complex for purine biosynthesis. Nat. Chem. Biol. 7 (2011), 909–915.
51. 51 Fang, Y., et al. G-protein-coupled receptor regulation of de novo purine biosynthesis: a novel druggable mechanism. Biotechnol. Genet. Eng. Rev. 29 (2013), 31–48.
52. 52 Fu, R., et al. Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways. Mol. Genet. Metab. 114 (2015), 55–61.
53. 53 Beeckmans, S., Kanarek, L., Demonstration of physical interactions between consecutive enzymes of the citric acid cycle and of the aspartate-malate shuttle. A study involving fumarase, malate dehydrogenase, citrate synthesis and aspartate aminotransferase. Eur. J. Biochem. 117 (1981), 527–535.
54. 54 Velot, C., et al. Model of a quinary structure between Krebs TCA cycle enzymes: a model for the metabolon. Biochemistry 36 (1997), 14271–14276.
55. 55 Wu, F., Minteer, S., Krebs cycle metabolon: structural evidence of substrate channeling revealed by cross-linking and mass spectrometry. Angew. Chem. 54 (2015), 1851–1854.
56. 56 Wu, F., et al. Krebs cycle metabolon formation: metabolite concentration gradient enhanced compartmentation of sequential enzymes. Chem. Commun. 51 (2015), 1244–1247.
57. 57 An, S., et al. Microtubule-assisted mechanism for functional metabolic macromolecular complex formation. Proc. Natl. Acad. Sci. U.S.A. 107 (2010), 12872–12876.
58. 58 French, J.B., et al. Spatial colocalization and functional link of purinosomes with mitochondria. Science 351 (2016), 733–737.
59. 59 Nikkanen, J., et al. Mitochondrial DNA replication defects disturb cellular dNTP pools and remodel one-carbon metabolism. Cell Metab. 23 (2016), 635–648.
60. 60 Bao, X.R., et al. Mitochondrial dysfunction remodels one-carbon metabolism in human cells. Elife, 5, 2016, e10575.
61. 61 Ben-Sahra, I., et al. mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle. Science 351 (2016), 728–733.
62. 62 Duvel, K., et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell 39 (2010), 171–183.
63. 63 Ward, P.S., Thompson, C.B., Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21 (2012), 297–308.
64. 64 Pavlova, N.N., Thompson, C.B., The emerging hallmarks of cancer metabolism. Cell Metab. 23 (2016), 27–47.
65. 65 Robak, P., Robak, T., Older and new purine nucleoside analogs for patients with acute leukemias. Cancer Treat. Rev. 39 (2013), 851–861.
66. 66 Yoshida, G.J., Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J. Exp. Clin. Cancer Res., 34, 2015, 111.
67. 67 Sahasranaman, S., et al. Clinical pharmacology and pharmacogenetics of thiopurines. Eur. J. Clin. Pharmacol. 64 (2008), 753–767.
68. 68 Parker, W.B., Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. Chem. Rev. 109 (2009), 2880–2893.
69. 69 Allegra, C.J., et al. Evidence for direct inhibition of de novo purine synthesis in human MCF-7 breast cells as a principal mode of metabolic inhibition by methotrexate. J. Biol. Chem. 262 (1987), 13520–13526.
70. 70 Christopherson, R.I., et al. Inhibitors of de novo nucleotide biosynthesis as drugs. Accounts Chem. Res. 35 (2002), 961–971.
71. 71 Nilsson, R., et al. Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer. Nat. Commun., 5, 2014, 3128.
72. 72 Spurr, I.B., et al. Targeting tumour proliferation with a small-molecule inhibitor of AICAR transformylase homodimerization. Chembiochem 13 (2012), 1628–1634.
73. 73 Caino, M.C., Altieri, D.C., Disabling mitochondrial reprogramming in cancer. Pharmacol. Res. 102 (2015), 42–45.
74. 74 Caino, M.C., Altieri, D.C., Molecular pathways: mitochondrial reprogramming in tumor progression and therapy. Clin. Cancer Res. 22 (2016), 540–545.
75. 75 Kohnhorst, C.L., et al. Subcellular functions of proteins under fluorescence single-cell microscopy. Biochim. Biophys. Acta 1864 (2016), 77–84.
76. 76 Srere, P.A., The metabolon. Trends Biochem. Sci. 10 (1985), 109–110.
77. 77 Batke, J., et al. Substrate-induced dissociation of glycerol-3-phosphate dehydrogenase and its complex formation with fructose-bisphosphate aldolase. Eur. J. Biochem. 107 (1980), 389–394.
78. 78 Ovadi, J., et al. Kinetic pathways of formation and dissociation of the glycerol-3-phosphate dehydrogenase-fructose-1,6-bisphosphate aldolase complex. Biochem. J. 229 (1985), 57–62.
79. 79 Ovadi, J., et al. Interaction of the dissociable glycerol-3-phosphate dehydrogenase and fructose-1,6-bisphosphate aldolase. Quantitative analysis by an extrinsic fluorescence probe. Eur. J. Biochem. 133 (1983), 433–437.
80. 80 Vertessy, B., Ovadi, J., A simple approach to detect active-site-directed enzyme-enzyme interactions. The aldolase/glycerol-phosphate-dehydrogenase enzyme system. Eur. J. Biochem. 164 (1987), 655–659.
81. 81 Vertessy, B.G., et al. Modulation of the interaction between aldolase and glycerol-phosphate dehydrogenase by fructose phosphates. Biochim. Biophys. Acta 1078 (1991), 236–242.
82. 82 Puchulu-Campanella, E., et al. Identification of the components of a glycolytic enzyme metabolon on the human red blood cell membrane. J. Biol. Chem. 288 (2013), 848–858.
83. 83 Evans, D.R., Guy, H.I., Mammalian pyrimidine biosynthesis: fresh insights into an ancient pathway. J. Biol. Chem. 279 (2004), 33035–33038.
84. 84 Robitaille, A.M., et al. Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis. Science 339 (2013), 1320–1323.
85. 85 Spector, D.L., SnapShot: cellular bodies. Cell, 127, 2006, 1071.
86. 86 Ma, E.H., Jones, R.G., Cell growth. (TORC)ing up purine biosynthesis. Science 351 (2016), 670–671.
87. 87 Fang, Y., Label-free drug discovery. Front. Pharmacol., 5, 2014, 52.
88. 88 Ferrie, A.M., et al. Label-free functional selectivity assays. Methods Mol. Biol. 1272 (2015), 227–246.