S-(2-Succinyl)cysteine: A novel chemical modification of tissue proteins by a Krebs cycle intermediate
Abstract
S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fumarate can be used to chemically modify cysteine residues of proteins, resulting in the formation of S-(2-succinyl)cysteine or succinylation of these residues.
“For example, fumarate can be used to chemically modify cysteine residues of proteins, resulting in the formation of S-(2-succinyl)cysteine or succinylation of these residues (93).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [93]
High levels of fumarate can modify cysteine residues through succination, converting sulfhydryl groups on cysteine to S-(2-succinyl)-cysteine (2SC), in some cases interfering with protein function.
“Interestingly, because of its electrophilic properties, high levels of fumarate can modify cysteine residues through a process termed succination. This process converts sulfhydryl groups on cysteine to S-(2-succinyl)-cysteine (2SC), in some cases interfering with protein function (Alderson et al., 2006).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Alderson et al., 2006
Cites
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S.-I., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H.-P., et al. (2000) · Nature · doi:10.1038/35008121 · Cited by 4,277 · see citing works
All About Albumin: Biochemistry, Genetics, and Medical Applications
Peters, T. (1995) · Thammasat University Digital Collections · Cited by 3,089 · see citing works
Determination of hydroxyproline
Stegemann, H., & Stalder, K. (1967) · Clinica Chimica Acta · doi:10.1016/0009-8981(67)90167-2 · Cited by 1,588 · see citing works
Advanced glycation endproducts—role in pathology of diabetic complications
Ahmed, N. (2004) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2004.09.004 · Cited by 1,457 · see citing works
Understanding RAGE, the receptor for advanced glycation end products
Bierhaus, A., Humpert, P. M., Morcos, M., Wendt, T., Chavakis, T., Arnold, B., Stern, D. M., & Nawroth, P. P. (2005) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0688-7 · Cited by 1,297 · see citing works
Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products
Verzijl, N., DeGroot, J., Thorpe, S. R., Bank, R. A., Shaw, J., Lyons, T. J., Bijlsma, J. W. J., Lafeber, F. P. J. G., Baynes, J., & TeKoppele, J. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006700200 · Cited by 964 · see citing works
Self-citationDu, X., Matsumura, T., Edelstein, D., Rossetti, L., Zsengellér, Z. K., Szabó, C., & Brownlee, M. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18127 · Cited by 832 · see citing works
Sirover, M. A. (1999) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(99)00119-3 · Cited by 808 · see citing works
Wells‐Knecht, K. J., Zyzak, D. V., Litchfield, J., Thorpe, S. R., & Baynes, J. (1995) · Biochemistry · doi:10.1021/bi00011a027 · Cited by 594 · see citing works
Self-citationDinkova‐Kostova, A. T., Massiah, M. A., Bozak, R. E., Hicks, R. J., & Talalay, P. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051632198 · Cited by 594 · see citing works
Glomb, M. A., & Monnier, V. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.17.10017 · Cited by 576 · see citing works
Maillard reaction products in tissue proteins: New products and new perspectives
Thorpe, S. R., & Baynes, J. (2003) · Amino Acids · doi:10.1007/s00726-003-0017-9 · Cited by 543 · see citing works
Self-citationGlycoxidation and lipoxidation in atherogenesis
Baynes, J., & Thorpe, S. R. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00228-8 · Cited by 515 · see citing works
Self-citationThe macrophage scavenger receptor CD163
Fabriek, B. O., Dijkstra, C. D., & van den Berg, T. K. (2005) · Immunobiology · doi:10.1016/j.imbio.2005.05.010 · Cited by 456 · see citing works
Oxidation of Methionine in Proteins: Roles in Antioxidant Defense and Cellular Regulation
Levine, R. L., Moskovitz, J., & Stadtman, E. R. (2000) · IUBMB Life · doi:10.1080/713803735 · Cited by 446 · see citing works
The AGE Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes
Stitt, A. W., Gardiner, T. A., Anderson, N. L., Canning, P., Frizzell, N., Duffy, N., Boyle, C., Januszewski, A. S., Chachich, M. E., Baynes, J., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.9.2826 · Cited by 355 · see citing works
Self-citationCellular thiols and redox-regulated signal transduction
Sen, C. K. (2001) · Current topics in cellular regulation · doi:10.1016/s0070-2137(01)80001-7 · Cited by 345 · see citing works
Ahmed, N., Dobler, D., Dean, M., & Thornalley, P. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410973200 · Cited by 314 · see citing works
Dunn, J. A., McCance, D. R., Thorpe, S. R., Lyons, T. J., & Baynes, J. (1991) · Biochemistry · doi:10.1021/bi00219a007 · Cited by 304 · see citing works
Self-citationThiols in Cellular Redox Signalling and Control
Moran, L. K., Gutteridge, J. M. C., & Quinlan, G. J. (2001) · Current Medicinal Chemistry · doi:10.2174/0929867013372904 · Cited by 256 · see citing works
The electrophile counterattack response: Protection against neoplasia and toxicity
Prestera, T., Zhang, Y., Spencer, S. R., Wilczak, C. A., & Talalay, P. (1993) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(93)90024-8 · Cited by 256 · see citing works
Intervention against the Maillard reaction in vivo
Monnier, V. M. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.08.014 · Cited by 196 · see citing works
Ahmed, N., & Thornalley, P. J. (2002) · Biochemical Journal · doi:10.1042/bj3640015 · Cited by 154 · see citing works
Oxidation of Zinc Finger Transcription Factors: Physiological Consequences
Webster, K. A., Prentice, H. M., & Bishopric, N. (2001) · Antioxidants and Redox Signaling · doi:10.1089/15230860152542916 · Cited by 145 · see citing works
The Maillard reaction in foods.
Kaanane, A., & Labuza, T. P. (1989) · PubMed · Cited by 131 · see citing works
Effect of Diabetes and Aging on Carboxymethyllysine Levels in Human Urine
Wells‐Knecht, K. J., Dunn, J. A., McFarland, K. F., McCance, D. R., Lyons, T. J., Thorpe, S. R., & Baynes, J. (1991) · Diabetes · doi:10.2337/diab.40.2.190 · Cited by 121 · see citing works
Self-citationGlycoxidation: the menace of diabetes and aging.
Vlassara, H., & Palace, M. R. (2003) · PubMed · Cited by 113 · see citing works
Involvement of maillard reactions in Alzheimer disease
Reddy, V. P., Obrenovich, M. E., Atwood, C., Perry, G. L., & Smith, M. A. (2002) · Neurotoxicity Research · doi:10.1080/1029840290007321 · Cited by 101 · see citing works
Resolution of human mercapt‐ and nonmercaptalbumin by high‐performance liquid chromatography
Sogami, M., NAGOKA, S., ERA, S., HONDA, M., & Noguchi, K. (1984) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1984.tb00933.x · Cited by 101 · see citing works
Proteomic Analysis of the Site Specificity of Glycation and Carboxymethylation of Ribonuclease
Brock, J. W. C., Hinton, D. J. S., Cotham, W. E., Metz, T., Thorpe, S. R., Baynes, J., & Ames, J. M. (2003) · Journal of Proteome Research · doi:10.1021/pr0340173 · Cited by 82 · see citing works
Self-citationChemical Modification of Proteins by Lipids in Diabetes
Baynes, J. (2003) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2003.179 · Cited by 77 · see citing works
Self-citationModulation of the Fumarases of Escherichia coli in Response to Oxidative Stress
Liochev, S. I., & Fridovich, I. (1993) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1993.1159 · Cited by 72 · see citing works
Chemical modification of muscle protein in diabetes
Alt, N., Carson, J. A., Alderson, N. L., Wang, Y., Nagai, R., Henle, T., Thorpe, S. R., & Baynes, J. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.03.012 · Cited by 62 · see citing works
Self-citationMercapturic acids in the biological monitoring of occupational exposure to chemicals
Perbellini, L., Veronese, N., & Princivalle, A. (2002) · Journal of Chromatography B · doi:10.1016/s1570-0232(02)00501-9 · Cited by 43 · see citing works
Nε-(carboxymethyl)lysine (CML) as a Biomarker of Oxidative Stress in Long-Lived Tissue Proteins
Shaw, J., Baynes, J., & Thorpe, S. R. (2003) · Humana Press eBooks · doi:10.1385/1-59259-173-6:129 · Cited by 34 · see citing works
Self-citationEffect of Glucose Concentration on Formation of AGEs in Erythrocytes in Vitro
Nagai, R., Deemer, E. K., Brock, J. W. C., Thorpe, S. R., & Baynes, J. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1333.018 · Cited by 21 · see citing works
Self-citationHypoxia: A succinate‐fumarate electron shuttle between peripheral cells and lung
Cascarano, J., Ades, I. Z., & O’Connor, J. D. (1976) · Journal of Experimental Zoology · doi:10.1002/jez.1401980204 · Cited by 19 · see citing works
LAI, R. K., & Goldman, P. (1992) · Metabolism · doi:10.1016/0026-0495(92)90216-w · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The role of antioxidants in the chemistry of oxidative stress: A review
Pisoschi, A. M., & Pop, A. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.04.040 · Cited by 2,844 · see citing works
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363 · see citing works
Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?
DeBerardinis, R. J., & Thompson, C. B. (2012) · Cell · doi:10.1016/j.cell.2012.02.032 · Cited by 858 · see citing works
Adam, J., Hatipoglu, E., O'Flaherty, L., Ternette, N., Sahgal, N., Lockstone, H., Baban, D., Nye, E., Stamp, G. W., Wolhuter, K., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.09.006 · Cited by 585 · see citing works
Self-citationMetabolic Responses to Reductive Stress
Xiao, W., & Loscalzo, J. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7803 · Cited by 467 · see citing works
Li, F., Long, H., Zhou, Z.-W., Luo, H., Xu, S., & Gao, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.910292 · Cited by 460 · see citing works
Oncometabolites: linking altered metabolism with cancer
Yang, M. H., Soga, T., & Pollard, P. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67228 · Cited by 424 · see citing works
Ooi, A., Wong, J.-C., Petillo, D., Roossien, D., Perrier-Trudova, V., Whitten, D., Min, B. W. H., Tan, M.-H., Zhang, Z., Yang, X. J., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.08.024 · Cited by 401 · see citing works
Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas
Castro‐Vega, L. J., Buffet, A., de Cubas, A. A., Cascón, A., Menara, M., Khalifa, E., Amar, L., Azriel, S., Bourdeau, I., Chabre, O., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt639 · Cited by 398 · see citing works
Fumarate induces vesicular release of mtDNA to drive innate immunity
Zecchini, V. R., Paupe, V., Herranz-Montoya, I., Janssen, J. J. E., Wortel, I. M. N., Morris, J. L., Ferguson, A., Chowdhury, S. R., Segarra‐Mondejar, M., Costa, A. S. H., et al. (2023) · Nature · doi:10.1038/s41586-023-05770-w · Cited by 336 · see citing works
The Metabolic Basis of Kidney Cancer
Linehan, W. M., Schmidt, L. S., Crooks, D. R., Wei, D., Srinivasan, R., Lang, M., & Ricketts, C. J. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1354 · Cited by 336 · see citing works
Oxidative Stress in Alzheimer’s Disease: Why Did Antioxidant Therapy Fail?
Persson, T., Popescu, B. O., & Cedazo-Mı́nguez, Á. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/427318 · Cited by 318 · see citing works
The Proto-oncometabolite Fumarate Binds Glutathione to Amplify ROS-Dependent Signaling
Sullivan, L. B., Martinez-Garcia, E., Nguyen, H., Mullen, A. R., Dufour, E., Sudarshan, S., Licht, J. D., Deberardinis, R. J., & Chandel, N. S. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.05.003 · Cited by 304 · see citing works
Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome–associated Renal Cancer
Chen, Y., Brannon, A. R., Toubaji, A., Dudas, M. E., Won, H. H., Al‐Ahmadie, H. A., Fine, S. W., Gopalan, A., Frizzell, N., Voss, M. H., et al. (2014) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000000163 · Cited by 277 · see citing works
Self-citationThe functional roles of TCA cycle metabolites in cancer
Eniafe, J., & Jiang, S. (2021) · Oncogene · doi:10.1038/s41388-020-01639-8 · Cited by 274 · see citing works
Mechanistic insights into the regulation of metabolic enzymes by acetylation
Xiong, Y., & Guan, K. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201202056 · Cited by 238 · see citing works
Protein Lysine Acylation and Cysteine Succination by Intermediates of Energy Metabolism
Lin, H., Su, X., & He, B. (2012) · ACS Chemical Biology · doi:10.1021/cb3001793 · Cited by 236 · see citing works
Linehan, W. M., & Rouault, T. A. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0304 · Cited by 223 · see citing works
Modification of Proteins by Metabolites in Immunity
Diskin, C., Ryan, T. A. J., & O'Neill, L. A. J. (2020) · Immunity · doi:10.1016/j.immuni.2020.09.014 · Cited by 214 · see citing works
Toxic Elements in Food: Occurrence, Binding, and Reduction Approaches
Hajeb, P., Sloth, J. J., Shakibazadeh, S., Mahyudin, N. A., & Afsah‐Hejri, L. (2014) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12068 · Cited by 204 · see citing works
Miller, V. J., Villamena, F. A., & Volek, J. S. (2018) · Journal of Nutrition and Metabolism · doi:10.1155/2018/5157645 · Cited by 200 · see citing works
The emerging role of fumarate as an oncometabolite
Yang, M., Soga, T., Pollard, P. J., & Adam, J. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00085 · Cited by 189 · see citing works
Redox proteomics: from protein modifications to cellular dysfunction and disease
Butterfield, D. A., & Dalle‐Donne, I. (2013) · Mass Spectrometry Reviews · doi:10.1002/mas.21404 · Cited by 180 · see citing works
Cheng, J., Yan, J., Liu, Y., Shi, J., Wang, H., Zhou, H., Zhou, Y., Zhang, T., Zhao, L., Meng, X., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.04.017 · Cited by 182 · see citing works
Oncometabolites: Unconventional triggers of oncogenic signalling cascades
Sciacovelli, M., & Frezza, C. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.025 · Cited by 177 · see citing works
Features and regulation of non-enzymatic post-translational modifications
Harmel, R. K., & Fiedler, D. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2575 · Cited by 163 · see citing works
Inhibition of Mitochondrial Aconitase by Succination in Fumarate Hydratase Deficiency
Ternette, N., Yang, M., Laroyia, M., Kitagawa, M., O’Flaherty, L., Wolhulter, K., Igarashi, K., Saito, K., Kato, K., Fischer, R., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.02.013 · Cited by 158 · see citing works
Self-citationTubulin Post-Translational Modifications and Microtubule Dynamics
Włoga, D., Joachimiak, E., & Fabczak, H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102207 · Cited by 163 · see citing works
Fumarate hydratase in cancer: A multifaceted tumour suppressor
Schmidt, C., Sciacovelli, M., & Frezza, C. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.002 · Cited by 163 · see citing works
Genetic predisposition to kidney cancer
Schmidt, L. S., & Linehan, W. M. (2016) · Seminars in Oncology · doi:10.1053/j.seminoncol.2016.09.001 · Cited by 160 · see citing works
Dimethyl fumarate, a two‐edged drug: Current status and future directions
Saidu, N. E. B., Kavian, N., Leroy, K., Jacob, C., Nicco, C., Batteux, F., & Alexandre, J. (2019) · Medicinal Research Reviews · doi:10.1002/med.21567 · Cited by 160 · see citing works
Hereditary leiomyomatosis and renal cell carcinoma
Schmidt, L. S., & Linehan, W. M. (2014) · International Journal of Nephrology and Renovascular Disease · doi:10.2147/ijnrd.s42097 · Cited by 155 · see citing works
Discovering the landscape of protein modifications
Keenan, E. K., Zachman, D. K., & Hirschey, M. D. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.015 · Cited by 154 · see citing works
Oncometabolites‐driven tumorigenesis: From genetics to targeted therapy
Morin, A., Letouzé, É., Gimenez‐Roqueplo, A., & Favier, J. (2014) · International Journal of Cancer · doi:10.1002/ijc.29080 · Cited by 150 · see citing works
Cui, C., Yang, F., & Li, Q. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.901565 · Cited by 143 · see citing works
Inactivation of Glyceraldehyde-3-Phosphate Dehydrogenase by Fumarate in Diabetes
Blatnik, M., Frizzell, N., Thorpe, S. R., & Baynes, J. (2007) · Diabetes · doi:10.2337/db07-0838 · Cited by 140 · see citing works
Self-citationChinopoulos, C., & Seyfried, T. N. (2018) · ASN NEURO · doi:10.1177/1759091418818261 · Cited by 128 · see citing works
A chemoproteomic portrait of the oncometabolite fumarate
Kulkarni, R. A., Bak, D. W., Wei, D., Bergholtz, S. E., Briney, C. A., Shrimp, J. H., Alpsoy, A., Thorpe, A. L., Bavari, A. E., Crooks, D. R., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-018-0217-y · Cited by 121 · see citing works
Self-citationSuccination of Protein Thiols during Adipocyte Maturation
Nagai, R., Brock, J. W. C., Blatnik, M., Baatz, J. E., Bethard, J. R., Walla, M. D., Thorpe, S. R., Baynes, J., & Frizzell, N. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703551200 · Cited by 122 · see citing works
Self-citationAlterations of metabolic genes and metabolites in cancer
Oermann, E. K., Wu, J., Guan, K., & Xiong, Y. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.01.013 · Cited by 122 · see citing works
Genetic alterations in Krebs cycle and its impact on cancer pathogenesis
Sajnani, K., Islam, F., Smith, R. A., Gopalan, V., & Lam, A. K.-Y. (2017) · Biochimie · doi:10.1016/j.biochi.2017.02.008 · Cited by 116 · see citing works
Fumarate hydratase (FH) and cancer: a paradigm of oncometabolism
Valcárcel-Jiménez, L., & Frezza, C. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02412-w · Cited by 115 · see citing works
Blatnik, M., Thorpe, S. R., & Baynes, J. W. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1433.047 · Cited by 109 · see citing works
Self-citationSuccination of Thiol Groups in Adipose Tissue Proteins in Diabetes
Frizzell, N., Rajesh, M. P., Jepson, M. J., Nagai, R., Carson, J. A., Thorpe, S. R., & Baynes, J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.019257 · Cited by 99 · see citing works
Self-citationReyes, C., Karamurzin, Y. S., Frizzell, N., Garg, K., Nonaka, D., Chen, Y., & Soslow, R. A. (2013) · Modern Pathology · doi:10.1038/modpathol.2013.215 · Cited by 98 · see citing works
Self-citationA role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia
Adam, J., Yang, M., Bauerschmidt, C., Kitagawa, M., O’Flaherty, L., Maheswaran, P., Özkan, G., Sahgal, N., Baban, D., Kato, K., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.04.006 · Cited by 97 · see citing works
Fumarate Hydratase Loss Causes Combined Respiratory Chain Defects
Tyrakis, P. A., Yurkovich, M. E., Sciacovelli, M., Papachristou, E. K., Bridges, H. R., Gaude, E., Schreiner, A., D’Santos, C. S., Hirst, J., Hernandez-Fernaud, J. R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.092 · Cited by 95 · see citing works
Post-translational modifications and their implications in cancer
Dutta, H., & Jain, N. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1240115 · Cited by 94 · see citing works
Rare insights into cancer biology
Adam, J., Yang, M., Soga, T., & Pollard, P. J. (2013) · Oncogene · doi:10.1038/onc.2013.222 · Cited by 88 · see citing works
Zhao, Q., Wang, Q., Yao, Q., Yang, Z., Li, W., Cheng, X., Wen, Y., Chen, R., Xu, J., Wang, X., et al. (2025) · Cell Research · doi:10.1038/s41422-024-01060-w · Cited by 88 · see citing works
‘Nothing of chemistry disappears in biology’: the Top 30 damage-prone endogenous metabolites
Lerma‐Ortiz, C., Jeffryes, J. G., Cooper, A. J. L., Niehaus, T. D., Thamm, A. M. K., Frelin, O., Aunins, T. R., Fiehn, O., de Crécy‐Lagard, V., Henry, C. S., et al. (2016) · Biochemical Society Transactions · doi:10.1042/bst20160073 · Cited by 87 · see citing works
Genetically-defined metabolic reprogramming in cancer
Mullen, A. R., & DeBerardinis, R. J. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.06.009 · Cited by 87 · see citing works
Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions
Guitart, A. V., Panagopoulou, T. I., Villacreces, A., Vukovic, M., Sepulveda, C., Allen, L., Carter, R. N., van de Lagemaat, L. N., Morgan, M., Giles, P., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20161087 · Cited by 86 · see citing works
Merkley, E. D., Metz, T., Smith, R. D., Baynes, J., & Frizzell, N. (2013) · Mass Spectrometry Reviews · doi:10.1002/mas.21382 · Cited by 84 · see citing works
Self-citationGe, X., Li, M.-D., Yin, J.-X., Shi, Z.-M., Fu, Y., Zhao, N.-W., Chen, H., Meng, L., Li, X., Hu, Z., et al. (2022) · Molecules and Cells · doi:10.1016/j.molcel.2022.01.029 · Cited by 67 · see citing works
Bennett, J. A., Weigelt, B., Chiang, S., Selenica, P., Chen, Y., Bialik, A., Bi, R., Schultheis, A. M., Lim, R. S., Ng, C. K. Y., et al. (2017) · Modern Pathology · doi:10.1038/modpathol.2017.56 · Cited by 77 · see citing works
Metabolic determinants of tumour initiation
Brunner, J. S., & Finley, L. W. S. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00773-5 · Cited by 76 · see citing works
GAPDH: Biological Properties and Diversity
Seidler, N. W. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-4716-6 · Cited by 71 · see citing works
Hypoxia-reprogrammed tricarboxylic acid cycle promotes the growth of human breast tumorigenic cells
Tang, K., Yu, Y., Zhu, L., Xu, P., Chen, J., Ma, J., Zhang, H., Fang, H., Sun, W., Zhou, L., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0932-1 · Cited by 66 · see citing works
Mito-Nuclear Communication by Mitochondrial Metabolites and Its Regulation by B-Vitamins
Janssen, J. J. E., Grefte, S., Keijer, J., & de Boer, V. C. J. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00078 · Cited by 68 · see citing works
Fumarate Hydratase Deletion in Pancreatic β Cells Leads to Progressive Diabetes
Adam, J., Ramracheya, R. D., Chibalina, M. V., Ternette, N., Hamilton, A., Tarasov, A. I., Zhang, Q., Rebelato, E., Rorsman, N. J. G., Martín-del-Río, R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.093 · Cited by 60 · see citing works
Self-citationMetabolic control of signalling pathways and metabolic auto‐regulation
Lorendeau, D., Christen, S., Rinaldi, G., & Fendt, S. (2015) · Biology of the Cell · doi:10.1111/boc.201500015 · Cited by 59 · see citing works
The Succinated Proteome of FH-Mutant Tumours
Yang, M. H., Ternette, N., Su, H., Dabiri, R., Kessler, B. M., Adam, J., Teh, B. T., & Pollard, P. J. (2014) · Metabolites · doi:10.3390/metabo4030640 · Cited by 60 · see citing works
Succination of proteins in diabetes
Frizzell, N., Lima, M., & Baynes, J. (2010) · Free Radical Research · doi:10.3109/10715762.2010.524643 · Cited by 59 · see citing works
Self-citationFrizzell, N., Thomas, S., Carson, J. A., & Baynes, J. (2012) · Biochemical Journal · doi:10.1042/bj20112142 · Cited by 58 · see citing works
Self-citationFH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer
Wilde, B. R., Chakraborty, N., Matulionis, N., Hernandez, S., Ueno, D., Gee, M. E., Esplin, E. D., Ouyang, K., Nykamp, K., Shuch, B. M., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0874 · Cited by 57 · see citing works
Skala, S. L., Dhanasekaran, S. M., & Mehra, R. (2018) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2018-0216-ra · Cited by 56 · see citing works
SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1–Nrf2
Burgener-Gasser, A.-V., Bantug, G. R., Meyer, B. J., Higgins, R., Ghosh, A., Bignucolo, O., Ma, E. H., Loeliger, J., Unterstab, G., Geigges, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0482-2 · Cited by 57 · see citing works
Smooth Muscle Tumors of the Female Genital Tract
Devereaux, K. A., & Schoolmeester, J. K. (2019) · Surgical pathology clinics · doi:10.1016/j.path.2019.02.004 · Cited by 54 · see citing works
Metabolic alterations in hereditary and sporadic renal cell carcinoma
Coffey, N. J., & Simon, M. C. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00800-2 · Cited by 54 · see citing works
Wei, C. (2024) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2024.111065 · Cited by 53 · see citing works
Ruecker, N., Jansen, R. S., Trujillo, C., Puckett, S. E., Jayachandran, P., Piroli, G. G., Frizzell, N., Molina, H., Rhee, K. Y., & Ehrt, S. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.01.005 · Cited by 53 · see citing works
Self-citationDetection of AGEs as markers for carbohydrate metabolism and protein denaturation
Nagai, R., Shirakawa, J., Fujiwara, Y., Ohno, R.-I., Moroishi, N., Sakata, N., & Nagai, M. (2014) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.13-112 · Cited by 50 · see citing works
Self-citationIdentification of protein succination as a novel modification of tubulin
Piroli, G. G., Manuel, A. M., Walla, M. D., Jepson, M. J., Brock, J. W. C., Rajesh, M. P., Tanis, R. M., Cotham, W. E., & Frizzell, N. (2014) · Biochemical Journal · doi:10.1042/bj20131581 · Cited by 48 · see citing works
Self-citationPiroli, G. G., Manuel, A. M., Patel, T., Walla, M. D., Shi, L., Lanci, S. A., Wang, J., Galloway, A. L., Ortinski, P. I., Smith, D. S., et al. (2018) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.000922 · Cited by 48 · see citing works
Self-citationFumarate suppresses B-cell activation and function through direct inactivation of LYN
Cheng, J., Liu, Y., Yan, J., Zhao, L., Zhou, Y., Shen, X.-Y., Chen, Y., Chen, Y., Meng, X., Zhang, X., et al. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01052-0 · Cited by 47 · see citing works
Functional implications of fumarate-induced cysteine succination
Guberović, I., & Frezza, C. (2024) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2024.05.003 · Cited by 48 · see citing works
Piroli, G. G., Manuel, A. M., Clapper, A. C., Walla, M. D., Baatz, J. E., Palmiter, R. D., Quintana, A., & Frizzell, N. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.051516 · Cited by 47 · see citing works
Self-citationSeo, A. N., Yoon, G., & Ro, J. Y. (2017) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000138 · Cited by 47 · see citing works
Fisch, F., Martinez-Fleites, C., Delenne, M., Baudendistel, N., Hauer, B., Turkenburg, J. P., Hart, S., Bruce, N. C., & Grogan, G. (2010) · Journal of the American Chemical Society · doi:10.1021/ja1053576 · Cited by 47 · see citing works
Thomas, S., Storey, K. B., Baynes, J., & Frizzell, N. (2011) · Obesity · doi:10.1038/oby.2011.340 · Cited by 46 · see citing works
Self-citationMedower, C., Wen, L., & Johnson, W. W. (2008) · Chemical Research in Toxicology · doi:10.1021/tx700430n · Cited by 39 · see citing works
Renal cell carcinoma: translational aspects of metabolism and therapeutic consequences
Yang, O. C. Y., Maxwell, P. H., & Pollard, P. J. (2013) · Kidney International · doi:10.1038/ki.2013.245 · Cited by 38 · see citing works
Thornalley, P. J., & Rabbani, N. (2010) · Free Radical Research · doi:10.3109/10715762.2010.534162 · Cited by 38 · see citing works
Metabolic Drivers in Hereditary Cancer Syndromes
Sciacovelli, M., Schmidt, C., Maher, E. R., & Frezza, C. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033612 · Cited by 37 · see citing works
Mera, K., Nagai, M., Brock, J. W. C., Fujiwara, Y., Murata, T., Maruyama, T., Baynes, J., Otagiri, M., & Nagai, R. (2008) · Journal of Immunological Methods · doi:10.1016/j.jim.2008.02.002 · Cited by 37 · see citing works
Self-citationOoi, A., & Furge, K. A. (2012) · 癌症：英文版 · doi:10.5732/cjc.012.10102 · Cited by 37 · see citing works
Ahvenainen, T., Tolvanen, J., Kämpjärvi, K., Uimari, O., Ahtikoski, A., Mäkinen, N., Heikinheimo, O., Aaltonen, L. A., Karhu, A., Bützow, R., et al. (2021) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001826 · Cited by 35 · see citing works
Loecken, E. M., & Guengerich, F. P. (2007) · Chemical Research in Toxicology · doi:10.1021/tx7003618 · Cited by 35 · see citing works
Macklin, P. S., Yamamoto, A., Browning, L., Hofer, M., Adam, J., & Pugh, C. W. (2020) · The Journal of Pathology · doi:10.1002/path.5402 · Cited by 33 · see citing works
Niehaus, T. D., & Hillmann, K. B. (2020) · FEBS Journal · doi:10.1111/febs.15284 · Cited by 33 · see citing works
Manuel, A. M., Walla, M. D., Faccenda, A., Martin, S. L., Tanis, R. M., Piroli, G. G., Adam, J., Kantor, B., Mutus, B., Townsend, D. M., et al. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6853 · Cited by 31 · see citing works
Self-citationWu, G., Fan, X., Cheng, L., Chen, Z., Yi, Y., Liang, J., Huang, X., Yang, N., Yin, J., Guo, W., et al. (2025) · Science Advances · doi:10.1126/sciadv.adx6489 · Cited by 32 · see citing works
Coping with inevitable accidents in metabolism
Danchin, A. (2016) · Microbial Biotechnology · doi:10.1111/1751-7915.12461 · Cited by 29 · see citing works
Testa, U., Pelosi, E., & Castelli, G. (2020) · Medicines · doi:10.3390/medicines7080044 · Cited by 28 · see citing works
Pheochromocytoma: Gasping for Air
Jochmanová, I., Zhuang, Z., & Pacák, K. (2015) · Hormones and Cancer · doi:10.1007/s12672-015-0231-4 · Cited by 29 · see citing works
Dimethyl fumarate: targeting glycolysis to treat MS
Angiari, S., & O’Neill, L. A. (2018) · Cell Research · doi:10.1038/s41422-018-0045-3 · Cited by 27 · see citing works
Xia, W., Mao, Y., Xia, Z., Cheng, J., & Jiang, P. (2025) · Nature Microbiology · doi:10.1038/s41564-025-01985-x · Cited by 27 · see citing works
RetractedSignals from the Circle: Tricarboxylic Acid Cycle Intermediates as Myometabokines
Maurer, J., Hoene, M., & Weigert, C. (2021) · Metabolites · doi:10.3390/metabo11080474 · Cited by 27 · see citing works
Tanis, R. M., Piroli, G. G., Day, S. D., & Frizzell, N. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.10.012 · Cited by 27 · see citing works
Self-citation
- Authors
- Alderson, N. L., Wang, Y., Blatnik, M., Frizzell, N., Walla, M. D., Lyons, T. J., Alt, N., Carson, J. A., Nagai, R., Thorpe, S. R., & Baynes, J. W.
- Affiliations
- University of South Carolina (US)
- Oklahoma City VA Medical Center (US)
- Technische Universität Dresden (DE)
- Corresponding author
- Baynes, John W.
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 450
- Issue
- 1
- Pages
- 1-8
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W1964116613
- Cited by
- 202
- References
- 38
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 8 · 2023: 18 · 2022: 13 · 2021: 12 · 2020: 14 · 2019: 15 · 2018: 12 · 2017: 12 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 14 · 2012: 10
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Scholar Commons (University of South Carolina) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-19971)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- fumarate, Krebs cycle intermediates, protein chemical modification, Michael addition, cysteine sulfhydryl groups, advanced glycation end products, carboxymethyllysine, serum albumin
- MeSH terms
- Serum Albumin, Human, Animals, Citric Acid Cycle, Collagen, Cysteine, Diabetes Mellitus, Experimental, Female, Fumarates, Glyceraldehyde-3-Phosphate Dehydrogenases, Humans, Insulin, Muscle Proteins, Protein Processing, Post-Translational, Radiation-Protective Agents, Serum Albumin, Skin, Anticarcinogenic Agents, Glycation End Products, Advanced, Rats, Sprague-Dawley, Succinic Acid, Insulin, Long-Acting, Rats, Insulin, Regular, Human
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
