Acetate as a Metabolic and Epigenetic Modifier of Cancer Therapy

Journal of Cellular Biochemistry

Volumn 117, Issue 3, 2016, Pages 574-588

  Jaworski, Diane M ^a   Namboodiri, Aryan M A ^b   Moffett, John R ^b  

^a UNIVERSITY OF VERMONT COLLEGE OF MEDICINE   (United States)

^b UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES   (United States)

Author keywords

ACETYL COENZYME A; ACETYL CoA; ACETYL CoA SYNTHETASE; ACETYLATION; DEACETYLATION; FATTY ACID; GLYCERYL TRIACETATE; KETOGENIC DIET; KETONE BODY; METABOLISM; REVIEW

Indexed keywords

ACETIC ACID; ACETYL COENZYME A; ANTINEOPLASTIC AGENT; CALCIUM ACETATE; CHOLESTEROL; FATTY ACID; ISOENZYME; KETONE BODY; LONG CHAIN FATTY ACID COENZYME A LIGASE; TRIACETIN; ACETATE COENZYME A LIGASE; ACETIC ACID DERIVATIVE;

ANTIINFLAMMATORY ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CALORIC RESTRICTION; CANCER CELL; CANCER GROWTH; CANCER THERAPY; CARBON SOURCE; CARCINOGENESIS; CATABOLISM; DEACETYLATION; ENERGY METABOLISM; ENZYME ANALYSIS; ENZYME METABOLISM; EPIGENETICS; FATTY ACID SYNTHESIS; HISTONE ACETYLATION; HUMAN; KETOGENIC DIET; LIPOGENESIS; NEUROPROTECTION; OXIDATION KINETICS; PRIORITY JOURNAL; PROTEIN ACETYLATION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; ACETYLATION; ANIMAL; DIET THERAPY; DRUG EFFECTS; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; METABOLISM; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PHYSIOLOGY; PROTEIN PROCESSING;

ACETATE-COA LIGASE; ACETATES; ACETYL COENZYME A; ACETYLATION; ANIMALS; CARCINOGENESIS; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION;

EID: 84955321102     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.25305     Document Type: Article

References (86)

1. Allen BG, Bhatia SK, Anderson CM, Eichenberger-Gilmore JM, Sibenaller ZA, Mapuskar KA, Schoenfeld JD, Buatti JM, Spitz DR, Fath MA,. 2014. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism. Redox Biol 2C: 963-970.
2. Ariyannur PS, Moffett JR, Madhavarao CN, Arun P, Vishnu N, Jacobowitz DM, Hallows WC, Denu JM, Namboodiri AM,. 2010. Nuclear-cytoplasmic localization of acetyl coenzyme a synthetase-1 in the rat brain. J Comp Neurol 518: 2952-2977.
3. Arun P, Ariyannur PS, Moffett JR, Xing G, Hamilton K, Grunberg NE, Ives JA, Namboodiri AM,. 2010a. Metabolic acetate therapy for the treatment of traumatic brain injury. J Neurotrauma 27: 293-298.
4. Arun P, Madhavarao CN, Moffett JR, Hamilton K, Grunberg NE, Ariyannur P, Gahl WA, Anikster Y, Mog S, Hallows WC, Denu JM, Namboodiri AM,. 2010b. Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease. J Inherit Metab Dis 33: 195-210.
5. Baenke F, Peck B, Miess H, Schulze A,. 2013. Hooked on fat: The role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech 6: 1353-1363.
6. Bailey JW, Haymond MW, Miles JM,. 1991. Triacetin: A potential parenteral nutrient. J Parenter Enteral Nutr 15: 32-36.
7. Bhatt DP, Houdek HM, Watt JA, Rosenberger TA,. 2013. Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis. Neurochem Int 62: 296-305.
8. Brissette CA, Houdek HM, Floden AM, Rosenberger TA,. 2012. Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis. J Neuroinflammation 9: 249.
9. Cai L, Sutter BM, Li B, Tu BP,. 2011. Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol Cell 42: 426-437.
10. Chen R, Xu M, Nagati JS, Hogg RT, Das A, Gerard RD, Garcia JA,. 2015. The acetate/ACSS2 switch regulates HIF-2 stress signaling in the tumor cell microenvironment. PLoS ONE 10: e0116515.
11. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M,. 2009. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325: 834-840.
12. Comerford SA, Huang Z, Du X, Wang Y, Cai L, Witkiewicz AK, Walters H, Tantawy MN, Fu A, Manning HC, Horton JD, Hammer RE, McKnight SL, Tu BP,. 2014. Acetate dependence of tumors. Cell 159: 1591-1602.
13. Davie JR,. 2003. Inhibition of histone deacetylase activity by butyrate. J Nutr 133: 2485S-2493S.
14. Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ,. 2012. The warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell 48: 612-626.
15. Eisenberg T, Schroeder S, Andryushkova A, Pendl T, Küttner V, Bhuke lA, Mariño G, Pietrocola F, Harger A, Zimmermann A, Moustafa T, Sprenger A, Jany E, Büttner S, Carmona-Gutierrez D, Ruckenstuhl C, Ring J, Reichelt W, Schimmel K, Leeb T, Moser C, Schatz S, Kamolz LP, Magnes C, Sinner F, Sedej S, Fröhlich KU, Juhasz G, Pieber TR, Dengjel J, Sigrist SJ, Kroemer G, Madeo F,. 2014. Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme A stimulates autophagy and prolongs lifespan. Cell Metab 19: 431-444.
16. Fan J, Kamphorst JJ, Rabinowitz JD, Shlomi T,. 2013. Fatty acid labeling from glutamine in hypoxia can be explained by isotope exchange without net reductive isocitrate dehydrogenase (IDH) flux. J Biol Chem 288: 31363-31369.
17. Feldman JL, Dittenhafer-Reed KE, Denu JM,. 2012. Sirtuin catalysis and regulation. J Biol Chem 287: 42419-42427.
18. Fiume MZ, CIRE Panel. 2003. Final report on the safety assessment of triacetin. Int J Toxicol 22 (Suppl 2): 1-10.
19. Flavin R, Peluso S, Nguyen PL, Loda M,. 2010. Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol 6: 551-562.
20. Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer N, Pérez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Imhof A, Caldas C, Jenuwein T, Esteller M,. 2005. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37: 391-400.
21. Fujino T, Kondo J, Ishikawa M, Morikawa K, Yamamoto TT,. 2001. Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate. J Biol Chem 276: 11420-11426.
22. Galluzzi L, Kepp O, Vander Heiden MG, Kroemer, G,. 2013. Metabolic targets for cancer therapy. Nat Rev Drug Discov 12: 829-846.
23. He H, Ke R, Lin H, Ying Y, Liu D, Luo Z,. 2015. Metformin, an old drug, brings a new era to cancer therapy. Cancer J 21: 70-74.
24. Hirschey MD, Shimazu T, Huang JY, Schwer B, Verdin E,. 2011. SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism. Cold Spring Harb Symp Quant Biol 76: 267-277.
25. Hopperton KE, Duncan RE, Bazinet RP, Archer MC,. 2014. Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity. Exp Cell Res 320: 302-310.
26. Hunt MC, Yamada J, Maltais LJ, Wright MW, Podesta EJ, Alexson SE,. 2005. A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases. J Lipid Res 46: 2029-2032.
27. Kamphorst JJ, Chung MK, Fan J, Rabinowitz JD,. 2014. Quantitative analysis of acetyl-CoA production in hypoxic cancer cells reveals substantial contribution from acetate. Cancer Metab 2: 23.
28. Kaul R, Casanova J, Johnson AB, Tang P, Matalon R,. 1991. Purification, characterization, and localization of aspartoacylase from bovine brain. J Neurochem 56: 129-135.
29. Kitange GJ, Mladek AC, Carlson BL, Schroeder MA, Pokorny JL, Cen L, Decker PA, Wu W, Lomberk GA, Gupta SK, Urrutia RA, Sarkaria JN,. 2012. Inhibition of histone deacetylation potentiates the evolution of acquired temozolomide resistance linked to MGMT upregulation in glioblastoma xenografts. Clin Cancer Res 18: 4070-4079.
30. Koppenol WH, Bounds PL, Dang CV,. 2011. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 11: 325-337.
31. Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, Xiong Y, Lei QY,. 2013. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell 51: 506-518.
32. Long PM, Moffett JR, Namboodiri AMA, Viapiano MS, Lawler SE, Jaworski DM,. 2013a. N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) promote growth and inhibit differentiation of glioma stem-like cells. J Biol Chem 288: 26188-26200.
33. Long PM, Tighe SW, Driscoll HE, Fortner KA, Viapiano MS, Jaworski DM,. 2015. Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest. J Cell Physiol 230: 1929-1943.
34. Long PM, Tighe SW, Driscoll HE, Moffett JR, Namboodiri AMA, Viapiano MS, Lawler SE, Jaworski DM,. 2013b. Acetate supplementation induces growth arrest of NG2/PDGFRα-positive oligodendroglioma-derived tumor-initiating cells. PLoS ONE 8: e80714.
35. Luong A, Hannah VC, Brown MS, Goldstein JL,. 2000. Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins. J Biol Chem 275: 26458-26466.
36. Maalouf M, Rho JM, Mattson MP,. 2009. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev 59: 293-315.
37. Madhavarao CN, Arun P, Anikster Y, Mog SR, Staretz-Chacham O, Moffett JR, Grunberg NE, Gahl WA, Namboodiri AM,. 2009. Glyceryl triacetate for Canavan disease: A low-dose trial in infants and evaluation of a higher dose for toxicity in the tremor rat model. J Inherit Metab Dis 32: 640-650.
38. Madhavarao CN, Arun P, Moffett JR, Szucs S, Surendran S, Matalon R, Garbern J, Hristova D, Johnson A, Jiang W, Namboodiri MA,. 2005. Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease. Proc Natl Acad Sci USA 102: 5221-5226.
39. Mariño G, Pietrocola F, Eisenberg T, Kong Y, Malik SA, Andryushkova A, Schroeder S, Pendl T, Harger A, Niso-Santano M, Zamzami N, Scoazec M, Durand S, Enot DP, Fernández ÁF, Martins I, Kepp O, Senovilla L, Bauvy C, Morselli E, Vacchelli E, Bennetzen M, Magnes C, Sinner F, Pieber T, López-Otín C, Maiuri M, Codogno P, Andersen JS, Hill J, Madeo F, Kroemer G,. 2014. Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol Cell 53: 710-725.
40. Marouco D, Garabadgiu AV, Melino G, Barlev NA,. 2013. Lysine-specific modifications of p53: A matter of life and death? Oncotarget 4: 1556-1571.
41. Marques C, Oliveira CS, Alves S, Chaves SR, Coutinho OP, Côrte-Real M, Preto A,. 2013. Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release. Cell Death Dis 4: e507.
42. Martinez-Pastor B, Mostoslavsky R,. 2012. Sirtuins, metabolism, and cancer. Front Pharmacol 3: 22.
43. Mashimo T, Pichumani K, Vemireddy V, Hatanpaa KJ, Singh DK, Sirasanagandla S, Nannepaga S, Piccirillo SG, Kovacs Z, Foong C, Huang Z, Barnett S, Mickey BE, DeBerardinis RJ, Tu BP, Maher EA, Bachoo RM,. 2014. Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell 159: 1603-1614.
44. Mathew R, Arun P, Madhavarao CN, Moffett JR, Namboodiri MA,. 2005. Progress toward acetate supplementation therapy for Canavan disease: Glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain. J Pharmacol Exp Ther 315: 297-303.
45. Matusewicz L, Meissner J, Toporkiewicz M, Sikorski A,. 2015. The effect of statins on cancer cells-review. Tumour Biol 36: 4889-4904.
46. Maurer GD, Brucker DP, Bähr O, Harter PN, Hattingen E, Walenta S, Mueller-Klieser W, Steinbach JP, Rieger J,. 2011. Differential utilization of ketone bodies by neurons and glioma cell lines: A rationale for ketogenic diet as experimental glioma therapy. BMC Cancer 11: 315.
47. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, Kelleher JK, Vander Heiden MG, Iliopoulos O, Stenpanopoulos G,. 2011. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481: 380-384.
48. Moffett JR, Ariyannur P, Arun P, Namboodiri AMA,. 2014. N-acetylaspartate and N-acetylaspartylglutamate in central nervous system health and disease. In:, Stagg C, Rothman D, editors. Magnetic resonance spectroscopy. Amsterdam, Netherlands: Elsevier, Inc. pp 71-90.
49. Moffett JR, Arun P, Ariyannur PS, Namboodiri AM,. 2013. N-Acetylaspartate reductions in brain injury: Impact on post-injury neuroenergetics, lipid synthesis, and protein acetylation. Front Neuroenergetics 5: 11.
50. Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM,. 2007. N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology. Prog Neurobiol 81: 89-131.
51. Nebeling LC, Miraldi F, Shurin SB, Lerner E,. 1995. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 14: 202-208.
52. Persson B, Flinta C, von Heijne G, Jörnvall H,. 1985. Structures of N-terminally acetylated proteins. Eur J Biochem 152: 523-527.
53. Pietrocola F, Galluzzi L, Bravo-San Pedro JM, Madeo F, Kroemer G,. 2015. Acetyl Coenzyme A: A Central Metabolite and Second Messenger. Cell Metab 21: 805-821.
54. Poff AM, Ari C, Arnold P, Seyfried TN, D'Agostino DP,. 2014. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int J Cancer 135: 1711-1720.
55. Rae C, Fekete AD, Kashem MA, Nasrallah FA, Bröer S,. 2012. Metabolism, compartmentation, transport and production of acetate in the cortical brain tissue slice. Neurochem Res 37: 2541-2553.
56. Reisenauer CJ, Bhatt DP, Mitteness DJ, Slanczka ER, Gienger HM, Watt JA, Rosenberger TA,. 2011. Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation. J Neurochem 117: 264-274.
57. Robertson C, Goodman JC, Grossman RG, Claypool M, White A,. 1992. Dietary nonprotein calories and cerebral infarction size in rats. Stroke 23: 564-568.
58. Sakakibara I, Fujino T, Ishii M, Tanaka T, Shimosawa T, Miura S, Zhang W, Tokutake Y, Yamamoto J, Awano M, Iwasaki S, Motoike T, Okamura M, Inagaki T, Kita K, Ezaki O, Naito M, Kuwaki T, Chohnan S, Yamamoto TT, Hammer RE, Kodama T, Yanagisawa M, Sakai J,. 2009. Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2. Cell Metab 9: 191-202.
59. Schmidt M, Pfetzer N, Schwab M, Strauss I, Kämmerer U,. 2011. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial. Nutr Metab (Lond) 8: 54.
60. Schug ZT, Peck B, Jones DT, Zhang Q, Grosskurth S, Alam IS, Goodwin LM, Smethurst E, Mason S, Blyth K, McGarry L, James D, Shanks E, Kalna G, Saunders RE, Jiang M, Howell M, Lassailly F, Thin MZ, Spencer-Dene B, Stamp G, van den Broek NJ, Mackay G, Bulusu V, Kamphorst JJ, Tardito S, Strachan D, Harris AL, Aboagye EO, Critchlow SE, Wakelam MJ, Schulze A, Gottlieb E,. 2015. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 27: 57-71.
61. Segel R, Anikster Y, Zevin S, Steinberg A, Gahl WA, Fisher D, Staretz-Chacham O, Zimran A, Altarescu G,. 2011. A safety trial of high dose glyceryl triacetate for Canavan disease. Mol Genet Metab 103: 203-206.
62. Seyfried TN, Flores R, Poff AM, D'Agostino DP, Mukherjee P,. 2015. Metabolic therapy: A new paradigm for managing malignant brain cancer. Cancer Lett 356: 289-300.
63. Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P,. 2011. Metabolic management of brain cancer. Biochim Biophys Acta 1807: 577-594.
64. Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P,. 2003. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer 89: 1375-1382.
65. Seyfried TN, Shelton LM,. 2010. Cancer as a metabolic disease. Nutr Metab (Lond) 7: 7.
66. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RVJ, de Cabo R, Ulrich S, Akassoglou K, Verdin E,. 2013. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339: 211-214.
67. Singh BN, Zhang G, Hwa YL, Li J, Dowdy SC, Jiang SW,. 2010. Nonhistone protein acetylation as cancer therapy targets. Expert Rev Anticancer Ther 10: 935-954.
68. 2A receptor levels in rats subjected to neuroinflammation. J Neuroinflammation 11: 99.
69. Soliman ML, Rosenberger TA,. 2011. Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. Mol Cell Biochem 352: 173-180.
70. Soliman ML, Smith MD, Houdek HM, Rosenberger TA,. 2012. Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation. J Neuroinflammation 9: 51.
71. Stafford P, Abdelwahab MG, Kim DY, Preul MC, Rho JM, Scheck AC,. 2010. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab (Lond) 7: 74.
72. Tsen AR, Long PM, Driscoll HE, Davies MT, Teasdale BA, Penar PL, Pendlebury WW, Spees JL, Lawler SE, Viapiano MS, Jaworski DM,. 2014. Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma. Int J Cancer 134: 1300-1310.
73. Watkins PA, Maiguel D, Jia Z, Pevsner J,. 2007. Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J Lipid Res 48: 2736-2750.
74. Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB,. 2009. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324: 1076-1080.
75. West AC, Johnstone RW,. 2014. New and emerging HDAC inhibitors for cancer treatment. J Clin Invest 124: 30-39.
76. Woolf EC, Curley KL, Liu Q, Turner GH, Charlton JA, Preul MC, Scheck AC,. 2015. The ketogenic diet alters the hypoxic response and affects expression of proteins associated with angiogenesis, invasive potential and vascular permeability in a mouse glioma model. PLoS ONE 10: e0130357.
77. Woolf EC, Scheck AC,. 2015. The ketogenic diet for the treatment of malignant glioma. J Lipid Res 56: 5-10.
78. Xu M, Nagati JS, Xie J, Li J, Walters H, Moon YA, Gerard RD, Huang C, Comerford SA, Hammer RE, Horton JD, Chen R, Garcia JA,. 2014. An acetate switch regulates stress erythropoiesis. Nat Med 20: 1018-1026.
79. Yamashita H, Kaneyuki T, Tagawa K,. 2001. Production of acetate in the liver and its utilization in peripheral tissues. Biochim Biophys Acta 1532: 79-87.
80. Yoshii Y, Furukawa T, Yoshii H, Mori T, Kiyono Y, Waki A, Kobayashi M, Tsujikawa T, Kudo T, Okazawa H, Yonekura Y, Fujibayashi Y,. 2009a. Cytosolic acetyl-CoA synthetase affected tumor cell survival under hypoxia: The possible function in tumor acetyl-CoA/acetate metabolism. Cancer Sci 100: 821-827.
81. Yoshii Y, Waki A, Furukawa T, Kiyono Y, Mori T, Yoshii H, Kudo T, Okazawa H, Welch MJ, Fujibayashi Y,. 2009b. Tumor uptake of radiolabeled acetate reflects the expression of cytosolic acetyl-CoA synthetase: implications for the mechanism of acetate PET. Nucl Med Biol 36: 771-777.
82. Yun M, Bang SH, Kim JW, Park JY, Kim KS, Lee JD,. 2009. The importance of acetyl coenzyme A synthetase for 11C-acetate uptake and cell survival in hepatocellular carcinoma. J Nucl Med 50: 1222-1228.
83. Zhao D, Zou SW, Liu Y, Zhou X, Mo Y, Wang P, Xu YH, Dong B, Xiong Y, Lei QY, Guan KL,. 2013. Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell 23: 464-476.
84. Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL,. 2010. Regulation of cellular metabolism by protein lysine acetylation. Science 327: 1000-1004.
85. Zu XY, Zhang QH, Liu JH, Cao RX, Zhong J, Yi GH, Quan ZH, Pizzorno G,. 2012. ATP citrate lyase inhibitors as novel cancer therapeutic agents. Recent Pat Anticancer Drug Discov 7: 154-167.
86. Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, Seyfried TN,. 2010. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report. Nutr Metab (Lond) 7: 33.