N-lactoyl-amino acids are ubiquitous metabolites that originate from CNDP2-mediated reverse proteolysis of lactate and amino acids

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 21, 2015, Pages 6601-6606

  Jansen, Robert S ^a   Addie, Ruben ^a   Merkx, Remco ^a   Fish, Alexander ^a   Mahakena, Sunny ^a   Bleijerveld, Onno B ^a   Altelaar, Maarten ^a   IJlst, Lodewijk ^b   Wanders, Ronald J ^b   Borst, P ^a   Van De Wetering, Koen ^a  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

ABCC5; MRP5; Physical exercise; Unknown metabolites; Untargeted metabolomics

Indexed keywords

AMINO ACID; CYTOSOLIC NONSPECIFIC DIPEPTIDASE 2; DIPEPTIDASE; LACTIC ACID; N LACTOYL AMINO ACID; UNCLASSIFIED DRUG; ABCC5 PROTEIN, HUMAN; CNDP2 PROTEIN, HUMAN; LACTIC ACID DERIVATIVE; MULTIDRUG RESISTANCE PROTEIN;

ARTICLE; BIOSYNTHESIS; CATALYSIS; CONTROLLED STUDY; EMBRYO; HUMAN; HUMAN CELL; IN VITRO STUDY; METABOLITE; METABOLOMICS; PHENYLKETONURIA; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEOMICS; BLOOD; CYTOSOL; EXERCISE; HEK293 CELL LINE; METABOLISM; METABOLOME; PHYSIOLOGY;

MAMMALIA;

AMINO ACIDS; CYTOSOL; DIPEPTIDASES; EXERCISE; HEK293 CELLS; HUMANS; LACTATES; METABOLOME; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; PROTEOLYSIS;

EID: 84930221642     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1424638112     Document Type: Article

References (55)

1. Patti GJ, Yanes O, Siuzdak G (2012) Innovation: Metabolomics: The apogee of the omics trilogy. Nat Rev Mol Cell Biol 13(4):263-269.
2. Tautenhahn R, et al. (2012) An accelerated workflow for untargeted metabolomics using the METLIN database. Nat Biotechnol 30(9):826-828.
3. Wishart DS, et al. (2013) HMDB 3.0 - The Human Metabolome Database in 2013. Nucleic Acids Res 41(Database issue):D801-D807.
4. Fiehn O, Barupal DK, Kind T (2011) Extending biochemical databases by metabolomic surveys. J Biol Chem 286(27):23637-23643.
5. Shin S-Y, et al.; Multiple Tissue Human Expression Resource (MuTHER) Consortium (2014) An atlas of genetic influences on human blood metabolites. Nat Genet 46(6):543-550.
6. Langley RJ, et al. (2013) An integrated clinico-metabolomic model improves prediction of death in sepsis. Sci Transl Med 5(195):195ra95.
7. Psychogios N, et al. (2011) The human serum metabolome. PLoS ONE 6(2):e16957.
8. Bouatra S, et al. (2013) The human urine metabolome. PLoS ONE 8(9):e73076.
9. Kalisiak J, et al. (2009) Identification of a new endogenous metabolite and the characterization of its protein interactions through an immobilization approach. JAm Chem Soc 131(1):378-386.
10. Chen J, et al. (2008) Practical approach for the identification and isomer elucidation of biomarkers detected in a metabonomic study for the discovery of individuals at risk for diabetes by integrating the chromatographic and mass spectrometric information. Anal Chem 80(4):1280-1289.
11. Dunn WB, et al. (2013) Mass appeal: Metabolite identification in mass spectrometry-focused untargeted. Metabolomics 9(Suppl 1):S44-S66.
12. Borst P, Evers R, Kool M, Wijnholds J (2000) A family of drug transporters: The multidrug resistance-associated proteins. J Natl Cancer Inst 92(16):1295-1302.
13. Kool M, et al. (1997) Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res 57(16):3537-3547.
14. Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD (1998) Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J Natl Cancer Inst 90(22):1735-1741.
15. McAleer MA, Breen MA, White NL, Matthews N (1999) pABC11 (also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confer multidrug resistance when overexpressed in human embryonic kidney 293 cells. J Biol Chem 274(33):23541-23548.
16. Borst P, de Wolf C, van de Wetering K (2007) Multidrug resistance-associated proteins 3, 4, and 5. Pflugers Arch 453(5):661-673.
17. Reid G, et al. (2003) Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol 63(5):1094-1103.
18. Wielinga P, et al. (2005) The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res 65(10):4425-4430.
19. Jedlitschky G, Burchell B, Keppler D (2000) The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J Biol Chem 275(39):30069-30074.
20. Wielinga PR, et al. (2003) Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells. J Biol Chem 278(20):17664-17671.
21. Laue S, et al. (2014) cCMP is a substrate for MRP5. Naunyn Schmiedebergs Arch Pharmacol 387(9):893-895.
22. Mourskaia AA, et al. (2012) ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone. Breast Cancer Res 14(6):R149.
23. Nongpiur ME, et al. (2014) ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma. PLoS Genet 10(3):e1004089, and correction (2014) 10(4):e1004352.
24. Korolnek T, Zhang J, Beardsley S, Scheffer GL, Hamza I (2014) Control of metazoan heme homeostasis by a conserved multidrug resistance protein. Cell Metab 19(6): 1008-1019.
25. de Wolf CJF, et al. (2007) cGMP transport by vesicles from human and mouse erythrocytes. FEBS J 274(2):439-450.
26. van de Wetering K, Feddema W, Helms JB, Brouwers JF, Borst P (2009) Targeted metabolomics identifies glucuronides of dietary phytoestrogens as a major class of MRP3 substrates in vivo. Gastroenterology 137(5):1725-1735.
27. Krumpochova P, et al. (2012) Transportomics: Screening for substrates of ABC transporters in body fluids using vesicular transport assays. FASEB J 26(2):738-747.
28. Blau N, van Spronsen FJ, Levy HL (2010) Phenylketonuria. Lancet 376(9750):1417-1427.
29. Teufel M, et al. (2003) Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J Biol Chem 278(8):6521-6531.
30. Kaur H, Kumar C, Junot C, Toledano MB, Bachhawat AK (2009) Dug1p Is a Cys-Gly peptidase of the gamma-glutamyl cycle of Saccharomyces cerevisiae and represents a novel family of Cys-Gly peptidases. J Biol Chem 284(21):14493-14502.
31. Zhang Z, et al. (2014) Underexpressed CNDP2 participates in gastric cancer growth inhibition through activating the MAPK signaling pathway. Mol Med 20:17-28.
32. Lee J-H, et al. (2012) Loss of 18q22.3 involving the carboxypeptidase of glutamate-like gene is associated with poor prognosis in resected pancreatic cancer. Clin Cancer Res 18(2):524-533.
33. Zhang P, et al. (2006) Identification of carboxypeptidase of glutamate like-B as a candidate suppressor in cell growth and metastasis in human hepatocellular carcinoma. Clin Cancer Res 12(22):6617-6625.
34. Bordusa F (2002) Proteases in organic synthesis. Chem Rev 102(12):4817-4868.
35. Liebscher S, et al. (2014) N-terminal protein modification by substrate-activated reverse proteolysis. Angew Chem Int Ed Engl 53(11):3024-3028.
36. Berkers CR, de Jong A, Ovaa H, Rodenko B (2009) Transpeptidation and reverse proteolysis and their consequences for immunity. Int J Biochem Cell Biol 41(1):66-71.
37. Hagenfeldt L, Naglo AS (1987) New conjugated urinary metabolites in intermediate type maple syrup urine disease. Clin Chim Acta 169(1):77-83.
38. Henning C, Smuda M, Girndt M, Ulrich C, Glomb MA (2011) Molecular basis of maillard amide-advanced glycation end product (AGE) formation in vivo. J Biol Chem 286(52):44350-44356.
39. Smuda M, Glomb MA (2013) Fragmentation pathways during Maillard-induced carbohydrate degradation. J Agric Food Chem 61(43):10198-10208.
40. Frerot E, Chen T (2013) Identification and quantitation of new glutamic acid derivatives in soy sauce by UPLC/MS/MS. Chem Biodivers 10(10):1842-1850.
41. Sforza S, Cavatorta V, Galaverna G, Dossena A, Marchelli R (2009) Accumulation of non-proteolytic aminoacyl derivatives in Parmigiano-Reggiano cheese during ripening. Int Dairy J 19(10):582-587.
42. Sgarbi E, et al. (2013) Microbial origin of non proteolytic aminoacyl derivatives in long ripened cheeses. Food Microbiol 35(2):116-120.
43. Bottesini C, Tedeschi T, Dossena A, Sforza S (2014) Enzymatic production and degradation of cheese-derived non-proteolytic aminoacyl derivatives. Amino Acids 46(2): 441-447.
44. Nieman DC, Shanely RA, Gillitt ND, Pappan KL, Lila MA (2013) Serum metabolic signatures induced by a three-day intensified exercise period persist after 14 h of recovery in runners. J Proteome Res 12(10):4577-4584.
45. Pohjanen E, et al. (2007) A multivariate screening strategy for investigating metabolic effects of strenuous physical exercise in human serum. J Proteome Res 6(6):2113-2120.
46. Krug S, et al. (2012) The dynamic range of the human metabolome revealed by challenges. FASEB J 26(6):2607-2619.
47. Lewis WH, Truslove GM (1969) Electrophoretic heterogeneity of mouse erythrocyte peptidases. Biochem Genet 3(5):493-498.
48. Khersonsky O, Tawfik DS (2010) Enzyme promiscuity: A mechanistic and evolutionary perspective. Annu Rev Biochem 79:471-505.
49. Linster CL, Van Schaftingen E, Hanson AD (2013) Metabolite damage and its repair or pre-emption. Nat Chem Biol 9(2):72-80.
50. Veiga-da-Cunha M, Chevalier N, Stroobant V, Vertommen D, Van Schaftingen E (2014) Metabolite proofreading in carnosine and homocarnosine synthesis: Molecular identification of PM20D2 as β-alanyl-lysine dipeptidase. J Biol Chem 289(28):19726-19736.
51. Wijnholds J, et al. (2000) Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc Natl Acad Sci USA 97(13):7476-7481.
52. Jansen RS, et al. (2013) ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci USA 110(50):20206-20211.
53. Smith CA, Want EJ, O'Maille G, Abagyan R, Siuzdak G (2006) XCMS: Processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal Chem 78(3):779-787.
54. Böcker S, Letzel MC, Lipták Z, Pervukhin A (2009) SIRIUS: Decomposing isotope patterns for metabolite identification. Bioinformatics 25(2):218-224.
55. El-Sheikh AAK, van den Heuvel JJMW, Koenderink JB, Russel FGM (2007) Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J Pharmacol Exp Ther 320(1):229-235.