Abstract
The in vitro metabolic stability of histidine-dipeptides (HD), carnosine (CAR) and anserine (ANS), in human serum, and their absorption kinetics after ingesting pure carnosine or HD rich foods in humans have been investigated. Healthy women (n = 4) went through four phases of taking one dose of either 450 mg of pure carnosine, 150 g beef (B), 150 g chicken (C), or chicken broth (CB) from 150 g chicken with a >2-week washout period between each phase. Blood samples were collected at 0, 30, 60, 100, 180, 240, and 300 min, and urine samples before and after (up to 7 h) ingesting pure carnosine or food. Both plasma and urine samples were analyzed for HD concentrations using a sensitive and selective LC–ESI-MS/MS method. CAR was undetectable in plasma after ingesting pure carnosine, B, C or CB. By contrast, plasma ANS concentration was significantly increased (P < 0.05) after ingesting C or CB, respectively. Urinary concentrations of both CAR and ANS were 13- to 14-fold increased after ingesting B, and 14.8- and 243-fold after CB ingestion, respectively. Thus, dietary HD, which are rapidly hydrolyzed by carnosinase in plasma, and excreted in urine, may act as reactive carbonyl species sequestering agents.
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References
Abe H (2000) Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry (Mosc) 65:757–765
Aldini G, Carini M, Beretta G et al (2002) Carnosine is a quencher of 4-hydroxy-nonenal: through what mechanism of reaction? Biochem Biophys Res Commun 298:699–706. doi:10.1016/S0006-291X(02)02545-7
Aldini G, Orioli M, Carini M, Maffei Facino R (2004) Profiling histidine-containing dipeptides in rat tissues by liquid chromatography/electrospray ionization tandem mass spectrometry. J Mass Spectrom 39:1417–1428. doi:10.1002/jms.696
Aldini G, Facino RM, Beretta G, Carini M (2005) Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives. Biofactors 24:77–87. doi:10.1002/biof.5520240109
Alhamdani MS, Al-Azzawie HF, Abbas FK (2007) Decreased formation of advanced glycation end-products in peritoneal fluid by carnosine and related peptides. Perit Dial Int 27:86–89
Bonfanti L, Peretto P, De Marchis S, Fasolo A (1999) Carnosine-related dipeptides in the mammalian brain. Prog Neurobiol 59:333–353. doi:10.1016/S0301-0082(99)00010-6
Brownson C, Hipkiss AR (2000) Carnosine reacts with a glycated protein. Free Radic Biol Med 28:1564–1570. doi:10.1016/S0891-5849(00)00270-7
Carini M, Aldini G, Beretta G et al (2003) Acrolein-sequestering ability of endogenous dipeptides: characterization of carnosine and homocarnosine/acrolein adducts by electrospray ionization tandem mass spectrometry. J Mass Spectrom 38:996–1006. doi:10.1002/jms.517
Crush KG (1970) Carnosine and related substances in animal tissues. Comp Biochem Physiol 34:3–30. doi:10.1016/0010-406X(70)90049-6
Egorov S, Kurella EG, Boldyrev AA, Krasnovsky AA Jr (1997) Quenching of singlet molecular oxygen by carnosine and related antioxidants. Monitoring 1270-nm phosphorescence in aqueous media. Biochem Mol Biol Int 41:687–694
Gardner ML, Illingworth KM, Kelleher J, Wood D (1991) Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose. J Physiol 439:411–422
Gil-Agusti M, Esteve-Romero J, Carda-Broch S (2008) Anserine and carnosine determination in meat samples by pure micellar liquid chromatography. J Chromatogr A 1189:444–450. doi:10.1016/j.chroma.2007.11.075
Guiotto A, Calderan A, Ruzza P, Borin G (2005) Carnosine and carnosine-related antioxidants: a review. Curr Med Chem 12:2293–2315. doi:10.2174/0929867054864796
Harris RC, Tallon MJ, Dunnett M, Boobis L, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, Wise JA (2006) The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids 30:279–289. doi:10.1007/s00726-006-0299-9
Horinishi H, Grillo M, Margolis FL (1978) Purification and characterization of carnosine synthetase from mouse olfactory bulbs. J Neurochem 31:909–919. doi:10.1111/j.1471-4159.1978.tb00127.x
Jappar D, Hu Y, Keep RF, Smith DE (2009) Transport mechanisms of carnosine in SKPT cells: contribution of apical and basolateral membrane transporters. Pharm Res 26(1):172–181. doi:10.1007/s11095-008-9726-9
Kang JH, Kim KS, Choi SY et al (2002) Carnosine and related dipeptides protect human ceruloplasmin against peroxyl radical-mediated modification. Mol Cells 13:498–502
Kohen R, Yamamoto Y, Cundy KC, Ames BN (1988) Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proc Natl Acad Sci USA 85:3175–3179. doi:10.1073/pnas.85.9.3175
Kurata H, Fujii T, Tsutsui H et al (2006) Renoprotective effects of l-carnosine on ischemia/reperfusion-induced renal injury in rats. J Pharmacol Exp Ther 319:640–647. doi:10.1124/jpet.106.110122
Margolis FL (1974) Carnosine in the primary olfactory pathway. Science 184:909–911. doi:10.1126/science.184.4139.909
Min J, Senut MC, Rajanikant K et al (2008) Differential neuroprotective effects of carnosine, anserine, and N-acetyl carnosine against permanent focal ischemia. J Neurosci Res 86:2984–2991
Orioli M, Aldini G, Beretta G, Facino RM, Carini M (2005) LC–ESI-MS/MS determination of 4-hydroxy-trans-2-nonenal Michael adducts with cysteine and histidine-containing peptides as early markers of oxidative stress in excitable tissues. J Chromatogr B Analyt Technol Biomed Life Sci 827:109–118. doi:10.1016/j.jchromb.2005.04.025
Orioli M, Aldini G, Benfatto MC, Facino RM, Carini M (2007) HNE Michael adducts to histidine and histidine-containing peptides as biomarkers of lipid-derived carbonyl stress in urines: LC–MS/MS profiling in Zucker obese rats. Anal Chem 79:9174–9184. doi:10.1021/ac7016184
Park YJ, Volpe SL, Decker EA (2005) Quantitation of carnosine in humans plasma after dietary consumption of beef. J Agric Food Chem 53:4736–4739. doi:10.1021/jf047934h
Petroff OA, Hyder F, Rothman DL, Mattson RH (2001) Homocarnosine and seizure control in juvenile myoclonic epilepsy and complex partial seizures. Neurology 56:709–715
Rajanikant GK, Zemke D, Senut MC et al (2007) Carnosine is neuroprotective against permanent focal cerebral ischemia in mice. Stroke 38:3023–3031. doi:10.1161/STROKEAHA.107.488502
Rashid I, van Reyk DM, Davies MJ (2007) Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett 581:1067–1070. doi:10.1016/j.febslet.2007.01.082
Sauerhofer S, Yuan G, Braun GS et al (2007) l-carnosine, a substrate of carnosinase-1, influences glucose metabolism. Diabetes 56:2425–2432. doi:10.2337/db07-0177
Son DO, Satsu H, Kiso Y, Shimizu M (2004) Characterization of carnosine uptake and its physiological function in human intestinal epithelial Caco-2 cells. Biofactors 21:395–398. doi:10.1002/biof.552210177
Stuerenburg HJ (2000) The roles of carnosine in aging of skeletal muscle and in neuromuscular diseases. Biochemistry (Mosc) 65:862–865
Tang SC, Arumugam TV, Cutler RG et al (2007) Neuroprotective actions of a histidine analogue in models of ischemic stroke. J Neurochem 101:729–736. doi:10.1111/j.1471-4159.2006.04412.x
Teufel M, Saudek V, Ledig JP et al (2003) Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J Biol Chem 278:6521–6531. doi:10.1074/jbc.M209764200
Vistoli G, Pedretti A, Cattaneo M et al (2006) Homology modeling of human serum carnosinase, a potential medicinal target, and MD simulations of its allosteric activation by citrate. J Med Chem 49:3269–3277. doi:10.1021/jm0602099
Vistoli G, Orioli M, Pedretti A, Regazzoni L, Canevotti R, Negrisoli G, Carini M, Aldini G (2009) Design, synthesis, and evaluation of carnosine derivatives as selective and efficient sequestering agents of cytotoxic reactive carbonyl species. Chem Med Chem. doi:10.1002/cmdc.200800433
Wassif WS, Sherwood RA, Amir A et al (1994) Serum carnosinase activities in central nervous system disorders. Clin Chim Acta 225:57–64. doi:10.1016/0009-8981(94)90027-2
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This research has been supported by the U.S. Department of Agriculture, under agreement number 581950-9-001. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture.
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Yeum, KJ., Orioli, M., Regazzoni, L. et al. Profiling histidine dipeptides in plasma and urine after ingesting beef, chicken or chicken broth in humans. Amino Acids 38, 847–858 (2010). https://doi.org/10.1007/s00726-009-0291-2
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DOI: https://doi.org/10.1007/s00726-009-0291-2