SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion

Cell Metabolism

Volumn 25, Issue 4, 2017, Pages 838-855.e15

  Anderson, Kristin A ^a   Huynh, Frank K ^a   Fisher Wellman, Kelsey ^a   Stuart, J Darren ^a   Peterson, Brett S ^a   Douros, Jonathan D ^a   Wagner, Gregory R ^a   Thompson, J Will ^a   Madsen, Andreas S ^b   Green, Michelle F ^a   Sivley, R Michael ^c   Ilkayeva, Olga R ^a   Stevens, Robert D ^a   Backos, Donald S ^d   Capra, John A ^c   Olsen, Christian A ^b   Campbell, Jonathan E ^a   Muoio, Deborah M ^a   Grimsrud, Paul A ^a   Hirschey, Matthew D ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^d UNIVERSITY OF COLORADO   (United States)

Author keywords

branched chain amino acids; deacylase; insulin secretion; leucine; mitochondria; sirtuin 4

Indexed keywords

BIOLOGICAL MARKER; BOVINE SERUM ALBUMIN; BRANCHED CHAIN AMINO ACID; CITRATE SYNTHASE; COMPLEX III SUBUNIT 2; COMPLEX III SUBUNIT 5; COMPLEX V; CYTOCHROME C OXIDASE; GLUCOSE; INSULIN; IRON SULFUR PROTEIN; LEUCINE; LYSINE; METHYLCROTONOYL COENZYME A CARBOXYLASE; METHYLCROTONOYL COENZYME A CARBOXYLASE A; METHYLCROTONOYL COENZYME A CARBOXYLASE B; MITOCHONDRIAL PROTEIN; OXIDOREDUCTASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SIRTUIN 1; SIRTUIN 2; SIRTUIN 3; SIRTUIN 4; SIRTUIN 5; SIRTUIN 6; SIRTUIN 7; SUCCINATE DEHYDROGENASE (UBIQUINONE); UBIQUINOL CYTOCHROME C REDUCTASE; UNCLASSIFIED DRUG; AMIDASE; LIGASE; METHYLCROTONOYL-COA CARBOXYLASE; SIRT4 PROTEIN, MOUSE; SIRTUIN;

ACYLATION; AGING; ALPHA HELIX; AMINO ACID BLOOD LEVEL; AMINO ACID METABOLISM; AMINO ACID TRANSPORT; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BETA SHEET; CATABOLISM; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME SPECIFICITY; FEMALE; GLUCOSE HOMEOSTASIS; GLUCOSE INTOLERANCE; HUMAN; HUMAN CELL; INSULIN BLOOD LEVEL; INSULIN RELEASE; INSULIN RESISTANCE; LEUCINE METABOLISM; LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY; MALE; METABOLIC REGULATION; METABOLITE; MOLECULAR MODEL; MOUSE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PHYLOGENY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; PROTEOMICS; SIGNAL TRANSDUCTION; STRUCTURAL HOMOLOGY; STRUCTURE ANALYSIS; AMINO ACID SEQUENCE; ANIMAL; C57BL MOUSE; CHEMISTRY; HEK293 CELL LINE; HOMEOSTASIS; KNOCKOUT MOUSE; METABOLIC FLUX ANALYSIS; METABOLISM; SECRETION (PROCESS);

AMIDOHYDROLASES; AMINO ACID SEQUENCE; ANIMALS; CARBON-CARBON LIGASES; GLUCOSE; HEK293 CELLS; HOMEOSTASIS; HUMANS; INSULIN; INSULIN RESISTANCE; LEUCINE; LYSINE; METABOLIC FLUX ANALYSIS; MICE, INBRED C57BL; MICE, KNOCKOUT; MITOCHONDRIAL PROTEINS; MODELS, MOLECULAR; PHYLOGENY; SIRTUINS;

EID: 85016936100     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2017.03.003     Document Type: Article

References (83)

1. Ahuja, N., Schwer, B., Carobbio, S., Waltregny, D., North, B.J., Castronovo, V., Maechler, P., Verdin, E., Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J. Biol. Chem. 282 (2007), 33583–33592.
2. Allen, A., Kwagh, J., Fang, J., Stanley, C.A., Smith, T.J., Evolution of glutamate dehydrogenase regulation of insulin homeostasis is an example of molecular exaptation. Biochemistry 43 (2004), 14431–14443.
3. Anderson, K.A., Green, M.F., Huynh, F.K., Wagner, G.R., Hirschey, M.D., SnapShot: mammalian sirtuins. Cell 159 (2014), 956–956.e1.
4. Brooks, B.R., Brooks, C.L. 3rd, Mackerell, A.D. Jr., Nilsson, L., Petrella, R.J., Roux, B., Won, Y., Archontis, G., Bartels, C., Boresch, S., et al. CHARMM: the biomolecular simulation program. J. Comput. Chem. 30 (2009), 1545–1614.
5. Campbell, J.E., Ussher, J.R., Mulvihill, E.E., Kolic, J., Baggio, L.L., Cao, X., Liu, Y., Lamont, B.J., Morii, T., Streutker, C.J., et al. TCF1 links GIPR signaling to the control of beta cell function and survival. Nat. Med. 22 (2016), 84–90.
6. Capra, J.A., Singh, M., Characterization and prediction of residues determining protein functional specificity. Bioinformatics 24 (2008), 1473–1480.
7. Chen, C., Natale, D.A., Finn, R.D., Huang, H., Zhang, J., Wu, C.H., Mazumder, R., Representative proteomes: a stable, scalable and unbiased proteome set for sequence analysis and functional annotation. PLoS ONE, 6, 2011, e18910.
8. Clark, J.F., Kuznetsov, A.V., Radda, G.K., ADP-regenerating enzyme systems in mitochondria of guinea pig myometrium and heart. Am. J. Physiol. 272 (1997), C399–C404.
9. Coleman, D.L., Hummel, K.P., Hyperinsulinemia in pre-weaning diabetes (db) mice. Diabetologia 10:Suppl (1974), 607–610.
10. Csibi, A., Fendt, S.M., Li, C., Poulogiannis, G., Choo, A.Y., Chapski, D.J., Jeong, S.M., Dempsey, J.M., Parkhitko, A., Morrison, T., et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell 153 (2013), 840–854.
11. D'Antona, G., Ragni, M., Cardile, A., Tedesco, L., Dossena, M., Bruttini, F., Caliaro, F., Corsetti, G., Bottinelli, R., Carruba, M.O., et al. Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab. 12 (2010), 362–372.
12. Du, J., Jiang, H., Lin, H., Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogues and 32P-NAD. Biochemistry 48 (2009), 2878–2890.
13. Du, J., Zhou, Y., Su, X., Yu, J.J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J.H., Choi, B.H., et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334 (2011), 806–809.
14. Eswar, N., Eramian, D., Webb, B., Shen, M.Y., Sali, A., Protein structure modeling with MODELLER. Methods Mol. Biol. 426 (2008), 145–159.
15. Fahien, L.A., Macdonald, M.J., The complex mechanism of glutamate dehydrogenase in insulin secretion. Diabetes 60 (2011), 2450–2454.
16. Feig, M., Onufriev, A., Lee, M.S., Im, W., Case, D.A., Brooks, C.L. 3rd, Performance comparison of generalized born and Poisson methods in the calculation of electrostatic solvation energies for protein structures. J. Comput. Chem. 25 (2004), 265–284.
17. Feldman, J.L., Baeza, J., Denu, J.M., Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J. Biol. Chem. 288 (2013), 31350–31356.
18. Felig, P., Amino acid metabolism in man. Annu. Rev. Biochem. 44 (1975), 933–955.
19. Finn, R.D., Bateman, A., Clements, J., Coggill, P., Eberhardt, R.Y., Eddy, S.R., Heger, A., Hetherington, K., Holm, L., Mistry, J., et al. Pfam: the protein families database. Nucleic Acids Res. 42 (2014), D222–D230.
20. Frezza, C., Cipolat, S., Scorrano, L., Organelle isolation: functional mitochondria from mouse liver, muscle and cultured fibroblasts. Nat. Protoc. 2 (2007), 287–295.
21. Frye, R.A., Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem. Biophys. Res. Commun. 273 (2000), 793–798.
22. Gostimskaya, I.S., Grivennikova, V.G., Zharova, T.V., Bakeeva, L.E., Vinogradov, A.D., In situ assay of the intramitochondrial enzymes: use of alamethicin for permeabilization of mitochondria. Anal. Biochem. 313 (2003), 46–52.
23. Gray, S.L., Donald, C., Jetha, A., Covey, S.D., Kieffer, T.J., Hyperinsulinemia precedes insulin resistance in mice lacking pancreatic beta-cell leptin signaling. Endocrinology 151 (2010), 4178–4186.
24. Greiss, S., Gartner, A., Sirtuin/Sir2 phylogeny, evolutionary considerations and structural conservation. Mol. Cells 28 (2009), 407–415.
25. Haigis, M.C., Mostoslavsky, R., Haigis, K.M., Fahie, K., Christodoulou, D.C., Murphy, A.J., Valenzuela, D.M., Yancopoulos, G.D., Karow, M., Blander, G., et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126 (2006), 941–954.
26. Hall, J.A., Dominy, J.E., Lee, Y., Puigserver, P., The sirtuin family's role in aging and age-associated pathologies. J. Clin. Invest. 123 (2013), 973–979.
27. Hirschey, M.D., Old enzymes, new tricks: sirtuins are NAD(+)-dependent de-acylases. Cell Metab. 14 (2011), 718–719.
28. Ho, L., Titus, A.S., Banerjee, K.K., George, S., Lin, W., Deota, S., Saha, A.K., Nakamura, K., Gut, P., Verdin, E., Kolthur-Seetharam, U., SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK. Aging (Albany, N.Y.) 5 (2013), 835–849.
29. Hornbeck, P.V., Kornhauser, J.M., Tkachev, S., Zhang, B., Skrzypek, E., Murray, B., Latham, V., Sullivan, M., PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res. 40 (2012), D261–D270.
30. Houtkooper, R.H., Pirinen, E., Auwerx, J., Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol. 13 (2012), 225–238.
31. Huang, C.S., Ge, P., Zhou, Z.H., Tong, L., An unanticipated architecture of the 750-kDa α6β6 holoenzyme of 3-methylcrotonyl-CoA carboxylase. Nature 481 (2011), 219–223.
32. Hutson, S.M., Wallin, R., Hall, T.R., Identification of mitochondrial branched chain aminotransferase and its isoforms in rat tissues. J. Biol. Chem. 267 (1992), 15681–15686.
33. Imai, S., Armstrong, C.M., Kaeberlein, M., Guarente, L., Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403 (2000), 795–800.
34. Jeong, S.M., Xiao, C., Finley, L.W., Lahusen, T., Souza, A.L., Pierce, K., Li, Y.H., Wang, X., Laurent, G., German, N.J., et al. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 23 (2013), 450–463.
35. Jeong, S.M., Lee, A., Lee, J., Haigis, M.C., SIRT4 protein suppresses tumor formation in genetic models of Myc-induced B cell lymphoma. J. Biol. Chem. 289 (2014), 4135–4144.
36. Jiang, H., Khan, S., Wang, Y., Charron, G., He, B., Sebastian, C., Du, J., Kim, R., Ge, E., Mostoslavsky, R., et al. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496 (2013), 110–113.
37. Jin, L., Wei, W., Jiang, Y., Peng, H., Cai, J., Mao, C., Dai, H., Choy, W., Bemis, J.E., Jirousek, M.R., et al. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J. Biol. Chem. 284 (2009), 24394–24405.
38. Koscielny, G., Yaikhom, G., Iyer, V., Meehan, T.F., Morgan, H., Atienza-Herrero, J., Blake, A., Chen, C.K., Easty, R., Di Fenza, A., et al. The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data. Nucleic Acids Res. 42 (2014), D802–D809.
39. Laurent, G., de Boer, V.C., Finley, L.W., Sweeney, M., Lu, H., Schug, T.T., Cen, Y., Jeong, S.M., Li, X., Sauve, A.A., Haigis, M.C., SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation. Mol. Cell. Biol. 33 (2013), 4552–4561.
40. Laurent, G., German, N.J., Saha, A.K., de Boer, V.C.J., Davies, M., Koves, T.R., Dephoure, N., Fischer, F., Boanca, G., Vaitheesvaran, B., et al. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol. Cell 50 (2013), 686–698.
41. Lee, S., Effects of diazoxide on insulin secretion and metabolic efficiency in the db/db mouse. Life Sci. 28 (1981), 1829–1840.
42. Li, C., Najafi, H., Daikhin, Y., Nissim, I.B., Collins, H.W., Yudkoff, M., Matschinsky, F.M., Stanley, C.A., Regulation of leucine-stimulated insulin secretion and glutamine metabolism in isolated rat islets. J. Biol. Chem. 278 (2003), 2853–2858.
43. Lian, K., Du, C., Liu, Y., Zhu, D., Yan, W., Zhang, H., Hong, Z., Liu, P., Zhang, L., Pei, H., et al. Impaired adiponectin signaling contributes to disturbed catabolism of branched-chain amino acids in diabetic mice. Diabetes 64 (2015), 49–59.
44. Madsen, A.S., Olsen, C.A., Substrates for efficient fluorometric screening employing the NAD-dependent sirtuin 5 lysine deacylase (KDAC) enzyme. J. Med. Chem. 55 (2012), 5582–5590.
45. Madsen, A.S., Andersen, C., Daoud, M., Anderson, K.A., Laursen, J.S., Chakladar, S., Huynh, F.K., Colaço, A.R., Backos, D.S., Fristrup, P., et al. Investigating the sensitivity of NAD+-dependent sirtuin deacylation activities to NADH. J. Biol. Chem. 291 (2016), 7128–7141.
46. Mansfeld, J., Urban, N., Priebe, S., Groth, M., Frahm, C., Hartmann, N., Gebauer, J., Ravichandran, M., Dommaschk, A., Schmeisser, S., et al. Branched-chain amino acid catabolism is a conserved regulator of physiological ageing. Nat. Commun., 6, 2015, 10043.
47. Marcotte, P.A., Richardson, P.L., Guo, J., Barrett, L.W., Xu, N., Gunasekera, A., Glaser, K.B., Fluorescence assay of SIRT protein deacetylases using an acetylated peptide substrate and a secondary trypsin reaction. Anal. Biochem. 332 (2004), 90–99.
48. Martin, F.P., Spanier, B., Collino, S., Montoliu, I., Kolmeder, C., Giesbertz, P., Affolter, M., Kussmann, M., Daniel, H., Kochhar, S., Rezzi, S., Metabotyping of Caenorhabditis elegans and their culture media revealed unique metabolic phenotypes associated to amino acid deficiency and insulin-like signaling. J. Proteome Res. 10 (2011), 990–1003.
49. Mathias, R.A., Greco, T.M., Oberstein, A., Budayeva, H.G., Chakrabarti, R., Rowland, E.A., Kang, Y., Shenk, T., Cristea, I.M., Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell 159 (2014), 1615–1625.
50. Michishita, E., McCord, R.A., Berber, E., Kioi, M., Padilla-Nash, H., Damian, M., Cheung, P., Kusumoto, R., Kawahara, T.L., Barrett, J.C., et al. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452 (2008), 492–496.
51. Min, J., Landry, J., Sternglanz, R., Xu, R.M., Crystal structure of a SIR2 homolog-NAD complex. Cell 105 (2001), 269–279.
52. Miyo, M., Yamamoto, H., Konno, M., Colvin, H., Nishida, N., Koseki, J., Kawamoto, K., Ogawa, H., Hamabe, A., Uemura, M., et al. Tumour-suppressive function of SIRT4 in human colorectal cancer. Br. J. Cancer 113 (2015), 492–499.
53. Mostoslavsky, R., Chua, K.F., Lombard, D.B., Pang, W.W., Fischer, M.R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M.M., et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124 (2006), 315–329.
54. Nakagawa, T., Lomb, D.J., Haigis, M.C., Guarente, L., SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137 (2009), 560–570.
55. Nasrin, N., Wu, X., Fortier, E., Feng, Y., Bare’, O.C., Chen, S., Ren, X., Wu, Z., Streeper, R.S., Bordone, L., SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells. J. Biol. Chem. 285 (2010), 31995–32002.
56. Newgard, C.B., Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab. 15 (2012), 606–614.
57. Newgard, C.B., An, J., Bain, J.R., Muehlbauer, M.J., Stevens, R.D., Lien, L.F., Haqq, A.M., Shah, S.H., Arlotto, M., Slentz, C.A., et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 9 (2009), 311–326.
58. Papadopoulos, J.S., Agarwala, R., COBALT: constraint-based alignment tool for multiple protein sequences. Bioinformatics 23 (2007), 1073–1079.
59. Pei, J., Kim, B.H., Grishin, N.V., PROMALS3D: a tool for multiple protein sequence and structure alignments. Nucleic Acids Res. 36 (2008), 2295–2300.
60. Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., et al. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics 10 (2011), 1–10.
61. Price, M.N., Dehal, P.S., Arkin, A.P., FastTree 2—approximately maximum-likelihood trees for large alignments. PLoS ONE, 5, 2010, e9490.
62. Rajan, S., Shankar, K., Beg, M., Varshney, S., Gupta, A., Srivastava, A., Kumar, D., Mishra, R.K., Hussain, Z., Gayen, J.R., Gaikwad, A.N., Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte. J. Endocrinol. 230 (2016), 275–290.
63. Roe, C.R., Millington, D.S., Maltby, D.A., Identification of 3-methylglutarylcarnitine. A new diagnostic metabolite of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. J. Clin. Invest. 77 (1986), 1391–1394.
64. Rost, B., Liu, J., The PredictProtein server. Nucleic Acids Res. 31 (2003), 3300–3304.
65. Schuetz, A., Min, J., Antoshenko, T., Wang, C.L., Allali-Hassani, A., Dong, A., Loppnau, P., Vedadi, M., Bochkarev, A., Sternglanz, R., Plotnikov, A.N., Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin. Structure 15 (2007), 377–389.
66. Schwer, B., Bunkenborg, J., Verdin, R.O., Andersen, J.S., Verdin, E., Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc. Natl. Acad. Sci. USA 103 (2006), 10224–10229.
67. Sener, A., Malaisse, W.J., L-leucine and a nonmetabolized analogue activate pancreatic islet glutamate dehydrogenase. Nature 288 (1980), 187–189.
68. Shah, S.H., Bain, J.R., Muehlbauer, M.J., Stevens, R.D., Crosslin, D.R., Haynes, C., Dungan, J., Newby, L.K., Hauser, E.R., Ginsburg, G.S., et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet 3 (2010), 207–214.
69. Shimomura, Y., Honda, T., Shiraki, M., Murakami, T., Sato, J., Kobayashi, H., Mawatari, K., Obayashi, M., Harris, R.A., Branched-chain amino acid catabolism in exercise and liver disease. J. Nutr. 136:1, Suppl (2006), 250S–253S.
70. Sievers, F., Wilm, A., Dineen, D., Gibson, T.J., Karplus, K., Li, W., Lopez, R., McWilliam, H., Remmert, M., Söding, J., et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol., 7, 2011, 539.
71. Tan, M., Peng, C., Anderson, K.A., Chhoy, P., Xie, Z., Dai, L., Park, J., Chen, Y., Huang, H., Zhang, Y., et al. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 19 (2014), 605–617.
72. Tanny, J.C., Dowd, G.J., Huang, J., Hilz, H., Moazed, D., An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell 99 (1999), 735–745.
73. Verdin, E., Dequiedt, F., Fischle, W., Frye, R., Marshall, B., North, B., Measurement of mammalian histone deacetylase activity. Methods Enzymol. 377 (2004), 180–196.
74. Vizcaíno, J.A., Csordas, A., Del-Toro, N., Dianes, J.A., Griss, J., Lavidas, I., Mayer, G., Perez-Riverol, Y., Reisinger, F., Ternent, T., et al. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res., 44, 2016, 11033.
75. Wagner, G.R., Hirschey, M.D., Nonenzymatic protein acylation as a carbon stress regulated by sirtuin deacylases. Mol. Cell 54 (2014), 5–16.
76. Wagner, G.R., Payne, R.M., Widespread and enzyme-independent Nε-acetylation and Nε-succinylation of proteins in the chemical conditions of the mitochondrial matrix. J. Biol. Chem. 288 (2013), 29036–29045.
77. Wagner, G.R., Bhatt, D.P., O'Connell, T.M., Thompson, J.W., Dubois, L.G., Backos, D.S., Yang, H., Mitchell, G.A., Ilkayeva, O.R., Stevens, R.D., et al. A class of reactive acyl-CoA species reveals the nonenzymatic origins of protein acylation. Cell Metab. 25 (2017), 823–837 this issue.
78. Wegener, D., Wirsching, F., Riester, D., Schwienhorst, A., A fluorogenic histone deacetylase assay well suited for high-throughput activity screening. Chem. Biol. 10 (2003), 61–68.
79. White, J.D., Carter, J.P., Kezar, H.S., Stereoselective synthesis of the macrocycle segment of verrucarin. J. Org. Chem. 47 (1982), 929–932.
80. Wirth, M., Karaca, S., Wenzel, D., Ho, L., Tishkoff, D., Lombard, D.B., Verdin, E., Urlaub, H., Jedrusik-Bode, M., Fischle, W., Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases. Mitochondrion 13 (2013), 705–720.
81. Wishart, D.S., Jewison, T., Guo, A.C., Wilson, M., Knox, C., Liu, Y., Djoumbou, Y., Mandal, R., Aziat, F., Dong, E., et al. HMDB 3.0—The Human Metabolome Database in 2013. Nucleic Acids Res. 41 (2013), D801–D807.
82. Zhou, Y., Jetton, T.L., Goshorn, S., Lynch, C.J., She, P., Transamination is required for alpha-ketoisocaproate but not leucine to stimulate insulin secretion. J. Biol. Chem. 285 (2010), 33718–33726.
83. 32P-labeled NAD and thin-layer chromatography. Methods Mol. Biol. 1077 (2013), 179–189.