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Annual Review of Nutrition

Volume 43, 2023

Intestinal Amino Acid Transport and Metabolic Health

Abstract

Amino acids derived from protein digestion are important nutrients for the growth and maintenance of organisms. Approximately half of the 20 proteinogenic amino acids can be synthesized by mammalian organisms, while the other half are essential and must be acquired from the nutrition. Absorption of amino acids is mediated by a set of amino acid transporters together with transport of di- and tripeptides. They provide amino acids for systemic needs and for enterocyte metabolism. Absorption is largely complete at the end of the small intestine. The large intestine mediates the uptake of amino acids derived from bacterial metabolism and endogenous sources. Lack of amino acid transporters and peptide transporter delays the absorption of amino acids and changes sensing and usage of amino acids by the intestine. This can affect metabolic health through amino acid restriction, sensing of amino acids, and production of antimicrobial peptides.

Keyword(s): amino acids, digestion, epithelial cells, membrane transport, protein restriction
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2023-08-21
2024-05-02
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Literature Cited

  1. 1.
    Adibi SA, Mercer DW. 1973. Protein digestion in human intestine as reflected in luminal, mucosal, and plasma amino acid concentrations after meals. J. Clin. Investig. 52:1586–94
     [Google Scholar]
  2. 2.
    Ahmadi S, Xia S, Wu YS, Di Paola M, Kissoon R et al. 2018. SLC6A14, an amino acid transporter, modifies the primary CF defect in fluid secretion. eLife 7:e37963
     [Google Scholar]
  3. 3.
    Anderson CM, Ganapathy V, Thwaites DT. 2008. Human solute carrier SLC6A14 is the β-alanine carrier. J. Physiol. 586:4061–67
     [Google Scholar]
  4. 4.
    Anderson CM, Grenade DS, Boll M, Foltz M, Wake KA et al. 2004. H+/amino acid transporter 1 (PAT1) is the imino acid carrier: an intestinal nutrient/drug transporter in human and rat. Gastroenterology 127:1410–22
     [Google Scholar]
  5. 5.
    Anderson CM, Howard A, Walters JR, Ganapathy V, Thwaites DT. 2009. Taurine uptake across the human intestinal brush-border membrane is via two transporters: H+-coupled PAT1 (SLC36A1) and Na+- and Cl−-dependent TauT (SLC6A6). J. Physiol. 587:731–44
     [Google Scholar]
  6. 6.
    Asatoor AM, Cheng B, Edwards KD, Lant AF, Matthews DM et al. 1970. Intestinal absorption of two dipeptides in Hartnup disease. Gut 11:380–87
     [Google Scholar]
  7. 7.
    Asatoor AM, Craske J, London DR, Milne MD. 1963. Indole production in Hartnup disease. Lancet 1:126–28
     [Google Scholar]
  8. 8.
    Avissar NE, Ryan CK, Ganapathy V, Sax HC. 2001. Na+-dependent neutral amino acid transporter ATB0 is a rabbit epithelial cell brush-border protein. Am. J. Physiol. Cell Physiol. 281:C963–71
     [Google Scholar]
  9. 9.
    Avissar NE, Ziegler TR, Wang HT, Gu LH, Miller JH et al. 2001. Growth factors regulation of rabbit sodium-dependent neutral amino acid transporter ATB0 and oligopeptide transporter 1 mRNAs expression after enteretomy. JPEN J. Parenter. Enter. Nutr. 25:65–72
     [Google Scholar]
  10. 10.
    Babu E, Kanai Y, Chairoungdua A, Kim DK, Iribe Y et al. 2003. Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters. J. Biol. Chem. 278:43838–45
     [Google Scholar]
  11. 11.
    Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. 2007. Hepatic fibroblast growth factor 21 is regulated by PPARα and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 5:426–37
     [Google Scholar]
  12. 12.
    Bailey CG, Ryan RM, Thoeng AD, Ng C, King K et al. 2011. Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. J. Clin. Investig. 121:446–53
     [Google Scholar]
  13. 13.
    Barnard JA, Thaxter S, Kikuchi K, Ghishan FK. 1988. Taurine transport by rat intestine. Am. J. Physiol. 254:G334–38
     [Google Scholar]
  14. 14.
    Baron DN, Dent CE, Harris H, Hart EW, Jepson JB. 1956. Hereditary pellagra-like skin rash with temporary cerebellar ataxia, constant renal aminoaciduria and other bizarre biochemical features. Lancet 268:421–28
     [Google Scholar]
  15. 15.
    Bauch C, Forster N, Loffing-Cueni D, Summa V, Verrey F. 2003. Functional cooperation of epithelial heteromeric amino acid transporters expressed in Madin-Darby canine kidney cells. J. Biol. Chem. 278:1316–22
     [Google Scholar]
  16. 16.
    Bhutia YD, Mathew M, Sivaprakasam S, Ramachandran S, Ganapathy V. 2022. Unconventional functions of amino acid transporters: role in macropinocytosis (SLC38A5/SLC38A3) and diet-induced obesity/metabolic syndrome (SLC6A19/SLC6A14/SLC6A6). Biomolecules 12:235
     [Google Scholar]
  17. 17.
    Bodoy S, Martin L, Zorzano A, Palacin M, Estevez R, Bertran J. 2005. Identification of LAT4, a novel amino acid transporter with system L activity. J. Biol. Chem. 280:12002–11
     [Google Scholar]
  18. 18.
    Bodoy S, Sotillo F, Espino-Guarch M, Sperandeo MP, Ormazabal A et al. 2019. Inducible Slc7a7 knockout mouse model recapitulates lysinuric protein intolerance disease. Int. J. Mol. Sci. 20:5294
     [Google Scholar]
  19. 19.
    Bohmer C, Bröer A, Munzinger M, Kowalczuk S, Rasko JE et al. 2005. Characterization of mouse amino acid transporter B0AT1 (slc6a19). Biochem. J. 389:745–51
     [Google Scholar]
  20. 20.
    Boll M, Foltz M, Rubio-Aliaga I, Kottra G, Daniel H. 2002. Functional characterization of two novel mammalian electrogenic proton-dependent amino acid cotransporters. J. Biol. Chem. 277:22966–73
     [Google Scholar]
  21. 21.
    Borsani G, Bassi MT, Sperandeo MP, De Grandi A, Buoninconti A et al. 1999. SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat. Genet. 21:297–301
     [Google Scholar]
  22. 22.
    Boyd CA, Perring VS. 1981. Transamination and asymmetry in glutamate transport across the basolateral membrane of frog small intestine. Biosci. Rep. 1:851–56
     [Google Scholar]
  23. 23.
    Brandsch M. 2013. Drug transport via the intestinal peptide transporter PepT1. Curr. Opin. Pharmacol. 13:881–87
     [Google Scholar]
  24. 24.
    Braun D, Wirth EK, Wohlgemuth F, Reix N, Klein MO et al. 2011. Aminoaciduria, but normal thyroid hormone levels and signalling, in mice lacking the amino acid and thyroid hormone transporter Slc7a8. Biochem. J. 439:249–55
     [Google Scholar]
  25. 25.
    Brodin B, Nielsen CU, Steffansen B, Frokjaer S. 2002. Transport of peptidomimetic drugs by the intestinal di/tri-peptide transporter, PepT1. Pharmacol. Toxicol. 90:285–96
     [Google Scholar]
  26. 26.
    Bröer A, Juelich T, Vanslambrouck JM, Tietze N, Solomon PS et al. 2011. Impaired nutrient signaling and body weight control in a Na+ neutral amino acid cotransporter (Slc6a19)-deficient mouse. J. Biol. Chem. 286:26638–51
     [Google Scholar]
  27. 27.
    Bröer A, Klingel K, Kowalczuk S, Rasko JE, Cavanaugh J, Bröer S. 2004. Molecular cloning of mouse amino acid transport system B0, a neutral amino acid transporter related to Hartnup disorder. J. Biol. Chem. 279:24467–76
     [Google Scholar]
  28. 28.
    Bröer S, Bailey CG, Kowalczuk S, Ng C, Vanslambrouck JM et al. 2008. Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. J. Clin. Investig. 118:3881–92
     [Google Scholar]
  29. 29.
    Bröer S, Bröer A, Hansen JT, Bubb WA, Balcar VJ et al. 2007. Alanine metabolism, transport, and cycling in the brain. J. Neurochem. 102:1758–70
     [Google Scholar]
  30. 30.
    Brown-Borg HM, Buffenstein R. 2017. Cutting back on the essentials: Can manipulating intake of specific amino acids modulate health and lifespan?. Ageing Res. Rev. 39:87–95
     [Google Scholar]
  31. 31.
    Busch AE, Herzer T, Waldegger S, Schmidt F, Palacin M et al. 1994. Opposite directed currents induced by the transport of dibasic and neutral amino acids in Xenopus oocytes expressing the protein rBAT. J. Biol. Chem. 269:25581–86
     [Google Scholar]
  32. 32.
    Calonge MJ, Gasparini P, Chillaron J, Chillon M, Gallucci M et al. 1994. Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine. Nat. Genet. 6:420–25
     [Google Scholar]
  33. 33.
    Camargo SM, Makrides V, Virkki LV, Forster IC, Verrey F. 2005. Steady-state kinetic characterization of the mouse B0AT1 sodium-dependent neutral amino acid transporter. Pflugers Arch. 451:338–48
     [Google Scholar]
  34. 34.
    Camargo SM, Singer D, Makrides V, Huggel K, Pos KM et al. 2009. Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with Hartnup mutations. Gastroenterology 136:872–82
     [Google Scholar]
  35. 35.
    Cheeseman CI. 1983. Characteristics of lysine transport across the serosal pole of the anuran small intestine. J. Physiol. 338:87–97
     [Google Scholar]
  36. 36.
    Cheng Q, Shah N, Bröer A, Fairweather S, Jiang Y et al. 2017. Identification of novel inhibitors of the amino acid transporter B0AT1 (SLC6A19), a potential target to induce protein restriction and to treat type 2 diabetes. Br. J. Pharmacol. 174:468–82
     [Google Scholar]
  37. 37.
    Cheon CK, Lee BH, Ko JM, Kim HJ, Yoo HW. 2010. Novel mutation in SLC6A19 causing late-onset seizures in Hartnup disorder. Pediatr. Neurol. 42:369–71
     [Google Scholar]
  38. 38.
    Chillaron J, Estevez R, Mora C, Wagner CA, Suessbrich H et al. 1996. Obligatory amino acid exchange via systems bo,+-like and y+L-like. A tertiary active transport mechanism for renal reabsorption of cystine and dibasic amino acids. J. Biol. Chem. 271:17761–70
     [Google Scholar]
  39. 39.
    Christie GR, Ford D, Howard A, Clark MA, Hirst BH. 2001. Glycine supply to human enterocytes mediated by high-affinity basolateral GLYT1. Gastroenterology 120:439–48
     [Google Scholar]
  40. 40.
    Colliss JE, Levi AJ, Milne MD. 1963. Stature and nutrition in cystinuria and Hartnup disease. Br. Med. J. 1:590–92
     [Google Scholar]
  41. 41.
    Crane RK. 1965. Na+-dependent transport in the intestine and other animal tissues. Fed. Proc. 24:1000–6
     [Google Scholar]
  42. 42.
    Cusworth DC, Dent CE. 1960. Renal clearances of amino acids in normal adults and in patients with aminoaciduria. Biochem. J. 74:550–61
     [Google Scholar]
  43. 43.
    Daniel H. 2004. Molecular and integrative physiology of intestinal peptide transport. Annu. Rev. Physiol. 66:361–84
     [Google Scholar]
  44. 44.
    Danilczyk U, Sarao R, Remy C, Benabbas C, Stange G et al. 2006. Essential role for collectrin in renal amino acid transport. Nature 444:1088–91
     [Google Scholar]
  45. 45.
    Danthi SJ, Liang B, Smicker O, Coupland B, Gregory J et al. 2018. Identification and characterization of inhibitors of a neutral amino acid transporter, SLC6A19, using two functional cell-based assays. SLAS Discov. 24:111–20
     [Google Scholar]
  46. 46.
    Dave MH, Schulz N, Zecevic M, Wagner CA, Verrey F. 2004. Expression of heteromeric amino acid transporters along the murine intestine. J. Physiol. 558:597–610
     [Google Scholar]
  47. 47.
    Deelen J, Kettunen J, Fischer K, van der Spek A, Trompet S et al. 2019. A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals. Nat. Commun. 10:3346
     [Google Scholar]
  48. 48.
    Dello Strologo L, Pras E, Pontesilli C, Beccia E, Ricci-Barbini V et al. 2002. Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification. J. Am. Soc. Nephrol. 13:2547–53
     [Google Scholar]
  49. 49.
    Desai J, Patel B, Darji B, Gite A, Panchal N et al. 2021. Discovery of novel, potent and orally efficacious inhibitor of neutral amino acid transporter B0AT1 (SLC6A19). Bioorg. Med. Chem. Lett. 53:128421
     [Google Scholar]
  50. 50.
    Desjeux JF, Simell RO, Dumontier AM, Perheentupa J. 1980. Lysine fluxes across the jejunal epithelium in lysinuric protein intolerance. J. Clin. Investig. 65:1382–87
     [Google Scholar]
  51. 51.
    Deves R, Boyd CA. 1998. Transporters for cationic amino acids in animal cells: discovery, structure, and function. Physiol. Rev. 78:487–545
     [Google Scholar]
  52. 52.
    Deves R, Chavez P, Boyd CA. 1992. Identification of a new transport system (y+L) in human erythrocytes that recognizes lysine and leucine with high affinity. J. Physiol. 454:491–501
     [Google Scholar]
  53. 53.
    Di Giacopo A, Rubio-Aliaga I, Cantone A, Artunc F, Rexhepaj R et al. 2013. Differential cystine and dibasic amino acid handling after loss of function of the amino acid transporter b0,+AT (Slc7a9) in mice. Am. J. Physiol. Renal Physiol. 305:F1645–55
     [Google Scholar]
  54. 54.
    Dodd D, Spitzer MH, Van Treuren W, Merrill BD, Hryckowian AJ et al. 2017. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature 551:648–52
     [Google Scholar]
  55. 55.
    Eriksson A, Flach CF, Lindgren A, Kvifors E, Lange S. 2008. Five mucosal transcripts of interest in ulcerative colitis identified by quantitative real-time PCR: a prospective study. BMC Gastroenterol. 8:34
     [Google Scholar]
  56. 56.
    Eriksson A, Jennische E, Flach CF, Jorge A, Lange S 2008. Real-time PCR quantification analysis of five mucosal transcripts in patients with Crohn's disease. Eur. J. Gastroenterol. Hepatol. 20:290–96
     [Google Scholar]
  57. 57.
    Fairweather SJ, Okada S, Gauthier-Coles G, Javed K, Bröer A, Bröer S. 2021. A GC-MS/single-cell method to evaluate membrane transporter substrate specificity and signaling. Front. Mol. Biosci. 8:646574
     [Google Scholar]
  58. 58.
    Fan MZ, Matthews JC, Etienne NM, Stoll B, Lackeyram D, Burrin DG. 2004. Expression of apical membrane l-glutamate transporters in neonatal porcine epithelial cells along the small intestinal crypt-villus axis. Am. J. Physiol. Gastrointest. Liver Physiol. 287:G385–98
     [Google Scholar]
  59. 59.
    Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I et al. 2016. Decreased consumption of branched-chain amino acids improves metabolic health. Cell Rep. 16:520–30
     [Google Scholar]
  60. 60.
    Fotiadis D, Kanai Y, Palacin M. 2013. The SLC3 and SLC7 families of amino acid transporters. Mol. Aspects Med. 34:139–58
     [Google Scholar]
  61. 61.
    Fox M, Thier S, Rosenberg L, Kiser W, Segal S. 1964. Evidence against a single renal transport defect in cystinuria. N. Engl. J. Med. 270:556–61
     [Google Scholar]
  62. 62.
    Freeman TC, Ivens A, Baillie JK, Beraldi D, Barnett MW et al. 2012. A gene expression atlas of the domestic pig. BMC Biol. 10:90
     [Google Scholar]
  63. 63.
    Ganapathy V, Ganapathy ME, Leibach FH. 2000. Intestinal transport of peptides and amino acids. Current Topics in Membranes: Gastrointestinal Transport Molecular Physiology, Vol. 50 KE Barrett, M Donowitz 379–412. Cambridge, MA: Academic
     [Google Scholar]
  64. 64.
    Guetg A, Mariotta L, Bock L, Herzog B, Fingerhut R et al. 2015. Essential amino acid transporter Lat4 (Slc43a2) is required for mouse development. J. Physiol. 593:1273–89
     [Google Scholar]
  65. 65.
    Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM et al. 2009. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–95
     [Google Scholar]
  66. 66.
    Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H et al. 2012. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 487:477–81
     [Google Scholar]
  67. 67.
    Hatanaka T, Haramura M, Fei YJ, Miyauchi S, Bridges CC et al. 2004. Transport of amino acid-based prodrugs by the Na+- and Cl−-coupled amino acid transporter ATB0,+ and expression of the transporter in tissues amenable for drug delivery. J. Pharmacol. Exp. Ther. 308:1138–47
     [Google Scholar]
  68. 68.
    Henagan TM, Laeger T, Navard AM, Albarado D, Noland RC et al. 2016. Hepatic autophagy contributes to the metabolic response to dietary protein restriction. Metabolism 65:805–15
     [Google Scholar]
  69. 69.
    Howard A, Hirst BH. 2011. The glycine transporter GLYT1 in human intestine: expression and function. Biol. Pharm. Bull. 34:784–88
     [Google Scholar]
  70. 70.
    Huxtable RJ. 1992. Physiological actions of taurine. Physiol. Rev. 72:101–63
     [Google Scholar]
  71. 71.
    Ingersoll SA, Ayyadurai S, Charania MA, Laroui H, Yan Y, Merlin D. 2012. The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and inflammatory bowel disease. Am. J. Physiol. Gastrointest. Liver Physiol. 302:G484–92
     [Google Scholar]
  72. 72.
    Jando J, Camargo SMR, Herzog B, Verrey F. 2017. Expression and regulation of the neutral amino acid transporter B0AT1 in rat small intestine. PLOS ONE 12:e0184845
     [Google Scholar]
  73. 73.
    Javed K, Bröer S. 2019. Mice lacking the intestinal and renal neutral amino acid transporter SLC6A19 demonstrate the relationship between dietary protein intake and amino acid malabsorption. Nutrients 11:2024
     [Google Scholar]
  74. 74.
    Javed K, Cheng Q, Carroll AJ, Truong TT, Bröer S. 2018. Development of biomarkers for inhibition of SLC6A19 (B0AT1)—a potential target to treat metabolic disorders. Int. J. Mol. Sci. 19:3597
     [Google Scholar]
  75. 75.
    Jiang Y, Rose AJ, Sijmonsma TP, Bröer A, Pfenninger A et al. 2015. Mice lacking neutral amino acid transporter B0AT1 (Slc6a19) have elevated levels of FGF21 and GLP-1 and improved glycaemic control. Mol. Metab 4:406–17
     [Google Scholar]
  76. 76.
    Kanai Y, Fukasawa Y, Cha SH, Segawa H, Chairoungdua A et al. 2000. Transport properties of a system y+L neutral and basic amino acid transporter. Insights into the mechanisms of substrate recognition. J. Biol. Chem. 275:20787–93
     [Google Scholar]
  77. 77.
    Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R et al. 2005. FGF-21 as a novel metabolic regulator. J. Clin. Investig. 115:1627–35
     [Google Scholar]
  78. 78.
    Killer M, Wald J, Pieprzyk J, Marlovits TC, Low C. 2021. Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes. Sci. Adv. 7:eabk3259
     [Google Scholar]
  79. 79.
    Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H. 2001. Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J. Biol. Chem. 276:17221–28
     [Google Scholar]
  80. 80.
    Kleta R, Romeo E, Ristic Z, Ohura T, Stuart C et al. 2004. Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder. Nat. Genet. 36:999–1002
     [Google Scholar]
  81. 81.
    Kolodziejczak D, Spanier B, Pais R, Kraiczy J, Stelzl T et al. 2013. Mice lacking the intestinal peptide transporter display reduced energy intake and a subtle maldigestion/malabsorption that protects them from diet-induced obesity. Am. J. Physiol. Gastrointest. Liver Physiol. 304:G897–907
     [Google Scholar]
  82. 82.
    Kowalczuk S, Bröer A, Munzinger M, Tietze N, Klingel K, Bröer S. 2005. Molecular cloning of the mouse IMINO system: an Na+- and Cl−-dependent proline transporter. Biochem. J. 386:417–22
     [Google Scholar]
  83. 83.
    Kowalczuk S, Bröer A, Tietze N, Vanslambrouck JM, Rasko JE, Bröer S. 2008. A protein complex in the brush-border membrane explains a Hartnup disorder allele. FASEB J. 22:2880–87
     [Google Scholar]
  84. 84.
    Laeger T, Albarado DC, Burke SJ, Trosclair L, Hedgepeth JW et al. 2016. Metabolic responses to dietary protein restriction require an increase in FGF21 that is delayed by the absence of GCN2. Cell Rep. 16:707–16
     [Google Scholar]
  85. 85.
    Laeger T, Henagan TM, Albarado DC, Redman LM, Bray GA et al. 2014. FGF21 is an endocrine signal of protein restriction. J. Clin. Investig. 124:3913–22
     [Google Scholar]
  86. 86.
    Le Guellec B, Rousseau F, Bied M, Supplisson S 2022. Flux coupling, not specificity, shapes the transport and phylogeny of SLC6 glycine transporters. PNAS 119:e2205874119
     [Google Scholar]
  87. 87.
    Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW et al. 2014. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 19:407–17
     [Google Scholar]
  88. 88.
    Lucas M. 1983. Determination of acid surface pH in vivo in rat proximal jejunum. Gut 24:734–39
     [Google Scholar]
  89. 89.
    Mach N, Berri M, Esquerre D, Chevaleyre C, Lemonnier G et al. 2014. Extensive expression differences along porcine small intestine evidenced by transcriptome sequencing. PLOS ONE 9:e88515
     [Google Scholar]
  90. 90.
    Macronutr. Panel, Food Nutr. Board, Inst. Med 2005. Protein and amino acids. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids589–768. Washington, DC: The National Academies Press
     [Google Scholar]
  91. 91.
    Maenz DD, Chenu C, Breton S, Berteloot A. 1992. pH-dependent heterogeneity of acidic amino acid transport in rabbit jejunal brush border membrane vesicles. J. Biol. Chem. 267:1510–16
     [Google Scholar]
  92. 92.
    Maida A, Zota A, Sjoberg KA, Schumacher J, Sijmonsma TP et al. 2016. A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution. J. Clin. Investig. 126:3263–78
     [Google Scholar]
  93. 93.
    Maric S, Fluchter P, Guglielmetti LC, Staerkle RF, Sasse T et al. 2021. Plasma citrulline correlates with basolateral amino acid transporter LAT4 expression in human small intestine. Clin. Nutr. 40:2244–51
     [Google Scholar]
  94. 94.
    Mariotta L, Ramadan T, Singer D, Guetg A, Herzog B et al. 2012. T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control. J. Physiol. 590:6413–24
     [Google Scholar]
  95. 95.
    McCarthy CF, Borland JL Jr., Lynch HJ Jr., Owen EE, Tyor MP. 1964. Defective uptake of basic amino acids and l-cystine by intestinal mucosa of patients with cystinuria. J. Clin. Investig. 43:1518–24
     [Google Scholar]
  96. 96.
    McCole DF. 2010. The epithelial glycine transporter GLYT1: protecting the gut from inflammation. J. Physiol. 588:1033–34
     [Google Scholar]
  97. 97.
    Meier C, Ristic Z, Klauser S, Verrey F. 2002. Activation of system L heterodimeric amino acid exchangers by intracellular substrates. EMBO J. 21:580–89
     [Google Scholar]
  98. 98.
    Milne MD, Asatoor AM, Edwards KD, Loughridge LW. 1961. The intestinal absorption defect in cystinuria. Gut 2:323
     [Google Scholar]
  99. 99.
    Miyamoto Y, Tiruppathi C, Ganapathy V, Leibach FH. 1989. Active transport of taurine in rabbit jejunal brush-border membrane vesicles. Am. J. Physiol. 257:G65–72
     [Google Scholar]
  100. 100.
    Mizoguchi K, Cha SH, Chairoungdua A, Kim DK, Shigeta Y et al. 2001. Human cystinuria-related transporter: localization and functional characterization. Kidney Int. 59:1821–33
     [Google Scholar]
  101. 101.
    Munck BG. 1980. Lysine transport across the small intestine. Stimulating and inhibitory effects of neutral amino acids. J. Membr. Biol. 53:45–53
     [Google Scholar]
  102. 102.
    Munck BG. 1985. Transport of imino acids and non-alpha-amino acids across the brush-border membrane of the rabbit ileum. J. Membr. Biol. 83:15–24
     [Google Scholar]
  103. 103.
    Munck BG. 1985. Transport of neutral and cationic amino acids across the brush-border membrane of the rabbit ileum. J. Membr. Biol. 83:1–13
     [Google Scholar]
  104. 104.
    Munck BG, Munck LK. 1999. Effects of pH changes on systems ASC and B in rabbit ileum. Am. J. Physiol. 276:G173–84
     [Google Scholar]
  105. 105.
    Munck LK, Munck BG. 1994. Chloride-dependent intestinal transport of imino and beta-amino acids in the guinea pig and rat. Am. J. Physiol. 266:R997–1007
     [Google Scholar]
  106. 106.
    Nassl AM, Rubio-Aliaga I, Fenselau H, Marth MK, Kottra G, Daniel H. 2011. Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1. Am. J. Physiol. Gastrointest. Liver Physiol. 301:G128–37
     [Google Scholar]
  107. 107.
    Navarro-Garrido A, Kim YC, Oe Y, Zhang H, Crespo-Masip M et al. 2022. Aristolochic acid-induced nephropathy is attenuated in mice lacking the neutral amino acid transporter B0AT1 (Slc6a19). Am. J. Physiol. Renal. Physiol. 323:F455–67
     [Google Scholar]
  108. 108.
    Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schroder S et al. 2013. Rapamycin extends murine lifespan but has limited effects on aging. J. Clin. Investig. 123:3272–91
     [Google Scholar]
  109. 109.
    Nishimura T, Nakatake Y, Konishi M, Itoh N. 2000. Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim. Biophys. Acta 1492:203–6
     [Google Scholar]
  110. 110.
    Noguchi A, Nakamura K, Murayama K, Yamamoto S, Komatsu H et al. 2016. Clinical and genetic features of lysinuric protein intolerance in Japan. Pediatr. Int. 58:979–83
     [Google Scholar]
  111. 111.
    Oparija-Rogenmozere L, Rajendran A, Poncet N, Camargo SMR, Verrey F. 2020. Phosphorylation of mouse intestinal basolateral amino acid uniporter LAT4 is controlled by food-entrained diurnal rhythm and dietary proteins. PLOS ONE 15:e0233863
     [Google Scholar]
  112. 112.
    Oparija L, Rajendran A, Poncet N, Verrey F. 2019. Anticipation of food intake induces phosphorylation switch to regulate basolateral amino acid transporter LAT4 (SLC43A2) function. J. Physiol. 597:521–42
     [Google Scholar]
  113. 113.
    Palacin M, Borsani G, Sebastio G. 2001. The molecular bases of cystinuria and lysinuric protein intolerance. Curr. Opin. Genet. Dev. 11:328–35
     [Google Scholar]
  114. 114.
    Palacin M, Estevez R, Zorzano A. 1998. Cystinuria calls for heteromultimeric amino acid transporters. Curr. Opin. Cell Biol. 10:455–61
     [Google Scholar]
  115. 115.
    Peghini P, Janzen J, Stoffel W. 1997. Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration. EMBO J. 16:3822–32
     [Google Scholar]
  116. 116.
    Pfeiffer R, Rossier G, Spindler B, Meier C, Kuhn L, Verrey F. 1999. Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family. EMBO J. 18:49–57
     [Google Scholar]
  117. 117.
    Pineda M, Wagner CA, Bröer A, Stehberger PA, Kaltenbach S et al. 2004. Cystinuria-specific rBAT(R365W) mutation reveals two translocation pathways in the amino acid transporter rBAT-b0,+AT. Biochem. J. 377:665–74
     [Google Scholar]
  118. 118.
    Pitere RR, van Heerden MB, Pepper MS, Ambele MA. 2022. Slc7a8 deletion is protective against diet-induced obesity and attenuates lipid accumulation in multiple organs. Biology 11:311
     [Google Scholar]
  119. 119.
    Potthoff MJ, Inagaki T, Satapati S, Ding X, He T et al. 2009. FGF21 induces PGC-1α and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. PNAS 106:10853–58
     [Google Scholar]
  120. 120.
    Preston RL, Schaeffer JF, Curran PF. 1974. Structure-affinity relationships of substrates for the neutral amino acid transport system in rabbit ileum. J. Gen. Physiol. 64:443–67
     [Google Scholar]
  121. 121.
    Prodhan UK, Pundir S, Chiang VS, Milan AM, Barnett MPG et al. 2020. Comparable postprandial amino acid and gastrointestinal hormone responses to beef steak cooked using different methods: a randomised crossover trial. Nutrients 12:380
     [Google Scholar]
  122. 122.
    Rhoads JM, Wu G. 2009. Glutamine, arginine, and leucine signaling in the intestine. Amino Acids 37:111–22
     [Google Scholar]
  123. 123.
    Qiu B, Matthies D, Fortea E, Yu Z, Boudker O. 2021. Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport. Sci. Adv. 7:eabf5814
     [Google Scholar]
  124. 124.
    Rajantie J, Simell O, Perheentupa J. 1980. Intestinal absorption in lysinuric protein intolerance: impaired for diamino acids, normal for citrulline. Gut 21:519–24
     [Google Scholar]
  125. 125.
    Rajendran A, Poncet N, Oparija-Rogenmozere L, Herzog B, Verrey F. 2020. Tissue-specific deletion of mouse basolateral uniporter LAT4 (Slc43a2) reveals its crucial role in small intestine and kidney amino acid transport. J. Physiol. 598:5109–32
     [Google Scholar]
  126. 126.
    Ramadan T, Camargo SM, Herzog B, Bordin M, Pos KM, Verrey F. 2007. Recycling of aromatic amino acids via TAT1 allows efflux of neutral amino acids via LAT2–4F2hc exchanger. Pflugers Archiv 454:507–16
     [Google Scholar]
  127. 127.
    Ramadan T, Camargo SM, Summa V, Hunziker P, Chesnov S et al. 2006. Basolateral aromatic amino acid transporter TAT1 (Slc16a10) functions as an efflux pathway. J. Cellular Physiol. 206:771–79
     [Google Scholar]
  128. 128.
    Reig N, Chillaron J, Bartoccioni P, Fernandez E, Bendahan A et al. 2002. The light subunit of system bo,+ is fully functional in the absence of the heavy subunit. EMBO J. 21:4906–14
     [Google Scholar]
  129. 129.
    Rodriguez CF, Escudero-Bravo P, Diaz L, Bartoccioni P, Garcia-Martin C et al. 2021. Structural basis for substrate specificity of heteromeric transporters of neutral amino acids. PNAS 118:e2113573118
     [Google Scholar]
  130. 130.
    Romeo E, Dave MH, Bacic D, Ristic Z, Camargo SM et al. 2006. Luminal kidney and intestine SLC6 amino acid transporters of B0AT-cluster and their tissue distribution in Mus musculus. Am. J. Physiol. Renal. Physiol. 290:F376–83
     [Google Scholar]
  131. 131.
    Rotoli BM, Barilli A, Visigalli R, Ferrari F, Dall'Asta V. 2020. y+LAT1 and y+LAT2 contribution to arginine uptake in different human cell models: implications in the pathophysiology of lysinuric protein intolerance. J. Cell. Mol. Med. 24:921–29
     [Google Scholar]
  132. 132.
    Rowan AM, Moughan PJ, Wilson MN, Maher K, Tasman-Jones C. 1994. Comparison of the ileal and faecal digestibility of dietary amino acids in adult humans and evaluation of the pig as a model animal for digestion studies in man. Br. J. Nutr. 71:29–42
     [Google Scholar]
  133. 133.
    Ruffin M, Mercier J, Calmel C, Mesinele J, Bigot J et al. 2020. Update on SLC6A14 in lung and gastrointestinal physiology and physiopathology: focus on cystic fibrosis. Cell. Mol. Life Sci. 77:3311–23
     [Google Scholar]
  134. 134.
    Schultheis PJ, Clarke LL, Meneton P, Miller ML, Soleimani M et al. 1998. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Nat. Genet. 19:282–85
     [Google Scholar]
  135. 135.
    Segawa H, Fukasawa Y, Miyamoto K, Takeda E, Endou H, Kanai Y. 1999. Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity. J. Biol. Chem. 274:19745–51
     [Google Scholar]
  136. 136.
    Seow HF, Bröer S, Bröer A, Bailey CG, Potter SJ et al. 2004. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat. Genet. 36:1003–7
     [Google Scholar]
  137. 137.
    Sgritta M, Dooling SW, Buffington SA, Momin EN, Francis MB et al. 2019. Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder. Neuron 101:246–59.e6
     [Google Scholar]
  138. 138.
    Shen Y, Wang J, Li Y, Zhang Y, Tian R, Yan R. 2022. Structures of ACE2-SIT1 recognized by Omicron variants of SARS-CoV-2. Cell Discov. 8:123
     [Google Scholar]
  139. 139.
    Shih VE, Bixby EM, Alpers DH, Bartoscas CS, Thier SO. 1971. Studies of intestinal transport defect in Hartnup disease. Gastroenterology 61:445–53
     [Google Scholar]
  140. 140.
    Singer D, Camargo SM, Ramadan T, Schafer M, Mariotta L et al. 2012. Defective intestinal amino acid absorption in Ace2 null mice. Am. J. Physiol. Gastrointest. Liver Physiol. 303:G686–95
     [Google Scholar]
  141. 141.
    Singh S, Arthur S, Sundaram U. 2018. Unique regulation of Na-glutamine cotransporter SN2/SNAT5 in rabbit intestinal crypt cells during chronic enteritis. J. Cell. Mol. Med. 22:1443–51
     [Google Scholar]
  142. 142.
    Sloan JL, Mager S. 1999. Cloning and functional expression of a human Na+ and Cl−-dependent neutral and cationic amino acid transporter B0+. J. Biol. Chem. 274:23740–45
     [Google Scholar]
  143. 143.
    Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE et al. 2014. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 19:418–30
     [Google Scholar]
  144. 144.
    Solon-Biet SM, Mitchell SJ, Coogan SC, Cogger VC, Gokarn R et al. 2015. Dietary protein to carbohydrate ratio and caloric restriction: comparing metabolic outcomes in mice. Cell Rep. 11:1529–34
     [Google Scholar]
  145. 145.
    Spanier B, Rohm F. 2018. Proton coupled oligopeptide transporter 1 (PepT1) function, regulation, and influence on the intestinal homeostasis. Compr. Physiol. 8:843–69
     [Google Scholar]
  146. 146.
    Sperandeo MP, Annunziata P, Bozzato A, Piccolo P, Maiuri L et al. 2007. Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance. Am. J. Physiol. Cell Physiol. 293:C191–98
     [Google Scholar]
  147. 147.
    Sterchi EE, Woodley JF. 1980. Peptide hydrolases of the human small intestinal mucosa: distribution of activities between brush border membranes and cytosol. Clin. Chim. Acta 102:49–56
     [Google Scholar]
  148. 148.
    Stevens BR, Kaunitz JD, Wright EM. 1984. Intestinal transport of amino acids and sugars: advances using membrane vesicles. Annu. Rev. Physiol. 46:417–33
     [Google Scholar]
  149. 149.
    Stevens BR, Ross HJ, Wright EM. 1982. Multiple transport pathways for neutral amino acids in rabbit jejunal brush border vesicles. J. Membr. Biol. 66:213–25
     [Google Scholar]
  150. 150.
    Stevens BR, Wright EM. 1987. Kinetics of the intestinal brush border proline (Imino) carrier. J. Biol. Chem. 262:6546–51
     [Google Scholar]
  151. 151.
    Stroup BM, Marom R, Li X, Hsu CW, Chang CY et al. 2020. A global Slc7a7 knockout mouse model demonstrates characteristic phenotypes of human lysinuric protein intolerance. Hum. Mol. Genet. 29:2171–84
     [Google Scholar]
  152. 152.
    Takanaga H, Mackenzie B, Suzuki Y, Hediger MA. 2005. Identification of mammalian proline transporter SIT1 (SLC6A20) with characteristics of classical System IMINO. J. Biol. Chem. 280:8974–84
     [Google Scholar]
  153. 153.
    Teijema HL, van Gelderen HH, Giesberts MA, Laurent de Angulo MS. 1974. Dicarboxylic aminoaciduria: an inborn error of glutamate and aspartate transport with metabolic implications, in combination with a hyperprolinemia. Metabolism 23:115–23
     [Google Scholar]
  154. 154.
    Terada T, Shimada Y, Pan X, Kishimoto K, Sakurai T et al. 2005. Expression profiles of various transporters for oligopeptides, amino acids and organic ions along the human digestive tract. Biochem. Pharmacol. 70:1756–63
     [Google Scholar]
  155. 155.
    Thier S, Fox M, Segal S, Rosenberg LE. 1964. Cystinuria: in vitro demonstration of an intestinal transport defect. Science 143:482–84
     [Google Scholar]
  156. 156.
    Thwaites DT, Anderson CM. 2007. Deciphering the mechanisms of intestinal imino (and amino) acid transport: the redemption of SLC36A1. Biochim. Biophys. Acta 1768:179–97
     [Google Scholar]
  157. 157.
    Thwaites DT, Kennedy DJ, Raldua D, Anderson CM, Mendoza ME et al. 2002. H/dipeptide absorption across the human intestinal epithelium is controlled indirectly via a functional Na/H exchanger. Gastroenterology 122:1322–33
     [Google Scholar]
  158. 158.
    Torras-Llort M, Torrents D, Soriano-Garcia JF, Gelpi JL, Estevez R et al. 2001. Sequential amino acid exchange across b0,+-like system in chicken brush border jejunum. J. Membr. Biol. 180:213–20
     [Google Scholar]
  159. 159.
    Torrents D, Estevez R, Pineda M, Fernandez E, Lloberas J et al. 1998. Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance. J. Biol. Chem. 273:32437–45
     [Google Scholar]
  160. 160.
    Torrents D, Mykkanen J, Pineda M, Feliubadalo L, Estevez R et al. 1999. Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. Nat. Genet. 21:293–96
     [Google Scholar]
  161. 161.
    Trautman ME, Richardson NE, Lamming DW. 2022. Protein restriction and branched-chain amino acid restriction promote geroprotective shifts in metabolism. Aging Cell 21:e13626
     [Google Scholar]
  162. 162.
    Tumer E, Bröer A, Balkrishna S, Julich T, Bröer S. 2013. Enterocyte-specific regulation of the apical nutrient transporter SLC6A19 (B0AT1) by transcriptional and epigenetic networks. J. Biol. Chem. 288:33813–23
     [Google Scholar]
  163. 163.
    Turner AJ, Tipnis SR, Guy JL, Rice G, Hooper NM. 2002. ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors. Can. J. Physiol. Pharmacol. 80:346–53
     [Google Scholar]
  164. 164.
    Utsunomiya-Tate N, Endou H, Kanai Y. 1996. Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J. Biol. Chem. 271:14883–90
     [Google Scholar]
  165. 165.
    van der Wielen N, Moughan PJ, Mensink M. 2017. Amino acid absorption in the large intestine of humans and porcine models. J. Nutr. 147:1493–98
     [Google Scholar]
  166. 166.
    Vandenberg RJ, Ryan RM. 2013. Mechanisms of glutamate transport. Physiol. Rev. 93:1621–57
     [Google Scholar]
  167. 167.
    Venkatesh M, Mukherjee S, Wang H, Li H, Sun K et al. 2014. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41:296–310
     [Google Scholar]
  168. 168.
    Viennois E, Pujada A, Zen J, Merlin D. 2018. Function, regulation, and pathophysiological relevance of the POT superfamily, specifically PepT1 in inflammatory bowel disease. Compr. Physiol. 8:731–60
     [Google Scholar]
  169. 169.
    Vuille-dit-Bille RN, Camargo SM, Emmenegger L, Sasse T, Kummer E et al. 2015. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. Amino Acids 47:693–705
     [Google Scholar]
  170. 170.
    Wang D, Ye J, Shi R, Zhao B, Liu Z et al. 2022. Dietary protein and amino acid restriction: roles in metabolic health and aging-related diseases. Free Radic. Biol. Med. 178:226–42
     [Google Scholar]
  171. 171.
    Wang X, Li XY, Piao Y, Yuan G, Lin Y et al. 2022. Hartnup disease presenting as hereditary spastic paraplegia and severe peripheral neuropathy. Am. J. Med. Genet. A 188:237–42
     [Google Scholar]
  172. 172.
    Wang Y, Song W, Wang J, Wang T, Xiong X et al. 2020. Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine. J. Exp. Med. 217:e20191130
     [Google Scholar]
  173. 173.
    Weissberg O, Elliott E. 2021. The mechanisms of CHD8 in neurodevelopment and autism spectrum disorders. Genes 12:1133
     [Google Scholar]
  174. 174.
    Wek RC, Jiang HY, Anthony TG. 2006. Coping with stress: eIF2 kinases and translational control. Biochem. Soc. Trans. 34:7–11
     [Google Scholar]
  175. 175.
    Widdows KL, Panitchob N, Crocker IP, Please CP, Hanson MA et al. 2015. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms. FASEB J. 29:2583–94
     [Google Scholar]
  176. 176.
    Windmueller HG, Spaeth AE. 1974. Uptake and metabolism of plasma glutamine by the small intestine. J. Biol. Chem. 249:5070–79
     [Google Scholar]
  177. 177.
    Wiseman G. 1974. Absorption of protein digestion products. Biomembranes, Intestinal Absorption, Vol. 4A DH Smyth 363–481. New York: Plenum Press
     [Google Scholar]
  178. 178.
    Wu D, Grund TN, Welsch S, Mills DJ, Michel M et al. 2020. Structural basis for amino acid exchange by a human heteromeric amino acid transporter. PNAS 117:21281–87
     [Google Scholar]
  179. 179.
    Wu G. 1998. Intestinal mucosal amino acid catabolism. J. Nutr. 128:1249–52
     [Google Scholar]
  180. 180.
    Yadav A, Shah N, Tiwari PK, Javed K, Cheng Q et al. 2020. Novel chemical scaffolds to inhibit the neutral amino acid transporter B0AT1 (SLC6A19), a potential target to treat metabolic diseases. Front. Pharmacol. 11:140
     [Google Scholar]
  181. 181.
    Yan R, Li Y, Shi Y, Zhou J, Lei J et al. 2020. Cryo-EM structure of the human heteromeric amino acid transporter b0,+AT-rBAT. Sci. Adv. 6:eaay6379
     [Google Scholar]
  182. 182.
    Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. 2020. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367:1444–48
     [Google Scholar]
  183. 183.
    Yan R, Zhou J, Li Y, Lei J, Zhou Q. 2020. Structural insight into the substrate recognition and transport mechanism of the human LAT2–4F2hc complex. Cell Discov. 6:82
     [Google Scholar]
  184. 184.
    Yap YW, Rusu PM, Chan AY, Fam BC, Jungmann A et al. 2020. Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution. Nat. Commun. 11:2894
     [Google Scholar]
  185. 185.
    Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME et al. 2021. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. Cell Metab. 33:905–22.e6
     [Google Scholar]
  186. 186.
    Yu Y, Zhang B, Ji P, Zuo Z, Huang Y et al. 2022. Changes to gut amino acid transporters and microbiome associated with increased E/I ratio in Chd8+/− mouse model of ASD-like behavior. Nat. Commun. 13:1151
     [Google Scholar]
  187. 187.
    Yu Z, Nan F, Wang LY, Jiang H, Chen W, Jiang Y. 2020. Effects of high-protein diet on glycemic control, insulin resistance and blood pressure in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Clin. Nutr. 39:1724–34
     [Google Scholar]
  188. 188.
    Zerangue N, Kavanaugh MP. 1996. Interaction of l-cysteine with a human excitatory amino acid transporter. J Physiol. 493:419–23
     [Google Scholar]
  189. 189.
    Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P et al. 2003. l-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Curr. Opin. Clin. Nutr. Metab. Care 6:229–40
     [Google Scholar]
  190. 190.
    Zhu Y, Chen L, He J, Chen Y, Gou H et al. 2018. Study of seizure-manifested Hartnup disorder case induced by novel mutations in SLC6A19. Open Life Sci. 13:22–27
     [Google Scholar]
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Intestinal Amino Acid Transport and Metabolic Health
Annual Review of Nutrition 43, 73 (2023); https://doi.org/10.1146/annurev-nutr-061121-094344
/content/journals/10.1146/annurev-nutr-061121-094344
/content/journals/10.1146/annurev-nutr-061121-094344
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