Lac-Phe
Iupacname(2S)-2-[-3-phenylpropanoic acid
OthernamesN-[(S)-lactoyl]-L-phenylalaninate
N-Lactoyl-phenylalanine
N-Lactoylphenylalanine

Lactoylphenylalanine, or Lac-Phe, is an N-lactoyl-amino acid metabolite produced by mammals and microorganisms.[1][2][3][4][5] In humans, levels are increased by intense exercise and in the inborn error of metabolism phenylketonuria.[6][7][8][1][9] In mice, high levels of Lac-Phe in the blood cause a decrease of food intake[6] and in humans, its production has been shown to correlate with adipose tissue loss during an endurance exercise intervention.[10] In mammals it is created from (S)-lactate and L-phenylalanine by the cytosol nonspecific dipeptidase (CNDP2) protein.[1] It is classified as N-acyl-alpha-amino acid and pseudodipeptide.[11]

It has also been reported that as an additive, N-L-lactoyl phenylalanine improves the taste of food, conferring an umami flavor.[12] It is found naturally in significant amounts in some traditional Chinese fermented foods such as preserved pickles and soy sauce,[13] and in Parmigiano-Reggiano cheese.[14] Oral intake of Lac-Phe does not have anti-obesity effects in mice, though intraperitoneal injection does reduce food intake and weight gain.[6] Activity dependent cell labeling indicates Lac-Phe activated neural populations in the hypothalamus and brainstem. [15]

See also

References

  1. ^ Jansen RS, Addie R, Merkx R, Fish A, Mahakena S, Bleijerveld OB, Altelaar M, IJlst L, Wanders RJ, Borst P, van de Wetering K (May 2015). "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. 112 (21): 6601–6606. Bibcode:2015PNAS..112.6601J. doi:10.1073/pnas.1424638112. PMC 4450436. PMID 25964343
  2. ^ Sgarbi, Elisa; Lazzi, Camilla; Iacopino, Luca; Bottesini, Chiara; Lambertini, Francesca; Sforza, Stefano; Gatti, Monica (2013-09-01). "Microbial origin of non proteolytic aminoacyl derivatives in long ripened cheeses". Food Microbiology. 35 (2): 116–120. doi:10.1016/j.fm.2013.02.013. hdl:11380/1281540. ISSN 0740-0020. PMID 23664262
  3. ^ Bottesini, Chiara; Tedeschi, Tullia; Dossena, Arnaldo; Sforza, Stefano (2014-02-01). "Enzymatic production and degradation of cheese-derived non-proteolytic aminoacyl derivatives". Amino Acids. 46 (2): 441–447. doi:10.1007/s00726-013-1637-3. ISSN 1438-2199. PMID 24337832
  4. ^ Feng, Junwei; Huang, Zikun; Huang, Mingtao; Cui, Chun; Zhao, Mouming; Feng, Yunzi (2024-11-30). "Revealing the Microbial Origins of N-Lactoyl Amino Acids in Soy Sauce: Synthesis Conditions, Potential Enzymes, and Utilization Preference". Journal of Agricultural and Food Chemistry. 73 (5): 3008–3015. doi:10.1021/acs.jafc.4c04907. ISSN 0021-8561. PMID 39614824
  5. ^ Xiao, Shuke; Li, Veronica L.; Long, Jonathan Z. (2024-08-01). "Lac-Phe (N-lactoyl-phenylalanine)". Trends in Endocrinology & Metabolism. 35 (8): 758–759. doi:10.1016/j.tem.2024.05.007. ISSN 1043-2760. PMC 11446501. PMID 39137723
  6. ^ Li VL, He Y, Contrepois K, Liu H, Kim JT, Wiggenhorn AL, Tanzo JT, Tung AS, Lyu X, Zushin PH, Jansen RS, Michael B, Loh KY, Yang AC, Carl CS, Voldstedlund CT, Wei W, Terrell SM, Moeller BC, Arthur RM, Wallis GA, van de Wetering K, Stahl A, Kiens B, Richter EA, Banik SM, Snyder MP, Xu Y, Long JZ (June 2022). "An exercise-inducible metabolite that suppresses feeding and obesity". Nature. 606 (7915): 785–790. Bibcode:2022Natur.606..785L. doi:10.1038/s41586-022-04828-5. PMC 9767481. PMID 35705806. S2CID 249710767
  7. ^ Wong C (15 June 2022). "Appetite-suppressing molecule helps obese mice lose weight". New Scientist. Retrieved 18 June 2022.
  8. ^ Reynolds G (15 June 2022). "Why Does a Hard Workout Make You Less Hungry?". The New York Times. Retrieved 18 June 2022.
  9. ^ Václavík, Jan; Coene, Karlien L. M.; Vrobel, Ivo; Najdekr, Lukáš; Friedecký, David; Karlíková, Radana; Mádrová, Lucie; Petsalo, Aleksanteri; Engelke, Udo F. H.; van Wegberg, Annemiek; Kluijtmans, Leo A. J.; Adam, Tomáš; Wevers, Ron A. (2018). "Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra". Journal of Inherited Metabolic Disease. 41 (3): 407–414. doi:10.1007/s10545-017-0109-4. ISSN 1573-2665. PMID 29139026
  10. ^ Hoene M, Zhao X, Machann J, Birkenfeld AL, Heni M, Peter A, Niess A, Moller A, Lehmann R, Xu G, Weigert C (January 2023). "Exercise-Induced N-Lactoylphenylalanine Predicts Adipose Tissue Loss during Endurance Training in Overweight and Obese Humans". Metabolites. 13 (1): 15. doi:10.3390/metabo13010015. PMC 9863672. PMID 36676940. S2CID 255077184
  11. ^ "Metabocard for N-Lactoylphenylalanine". The Human Metabolome Database (HMDB). The Metabolomics Innovation Centre (TIMC). HMDB0062175.
  12. ^ Feng, Junwei; Huang, Zikun; Cui, Chun; Zhao, Mouming; Feng, Yunzi (2024-10-01). "Synthesis, taste characteristics and taste mechanism of N-lactoyl leucine from soy sauce using sensory analysis and UPLC-MS/MS". Food Chemistry. 454. doi:10.1016/j.foodchem.2024.139670. ISSN 0308-8146. PMID 38820630
  13. ^ Wu J, Gao J, Lin J, Cui C, Li L, He S, Brennan C (May 2022). "Preparation and Taste Characteristics of Kokumi N-Lactoyl Phenylalanine in the Presence of Phenylalanine and Lactate". Journal of Agricultural and Food Chemistry. 70 (17): 5396–5407. Bibcode:2022JAFC...70.5396W. doi:10.1021/acs.jafc.2c00530. PMID 35452224. S2CID 248345604
  14. ^ Sforza, Stefano; Cavatorta, Valeria; Galaverna, Gianni; Dossena, Arnaldo; Marchelli, Rosangela (2009-10-01). "Accumulation of non-proteolytic aminoacyl derivatives in Parmigiano-Reggiano cheese during ripening". International Dairy Journal. 19 (10): 582–587. doi:10.1016/j.idairyj.2009.04.009. ISSN 0958-6946
  15. ^ Moya-Garzon MD, Wang M, Li VL, Lyu X, Wei W, Tung AS et al. (2024). "A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites.". Cell. 188 (1): 175–186.e20. doi:10.1016/j.cell.2024.10.032. PMC 11724754. PMID 39536746