ENTRY ko04974 Pathway NAME Protein digestion and absorption DESCRIPTION Protein is a dietary component essential for nutritional homeostasis in humans. Normally, ingested protein undergoes a complex series of degradative processes following the action of gastric, pancreatic and small intestinal enzymes. The result of this proteolytic activity is a mixture of amino acids and small peptides. Amino acids (AAs) are transported into the enterocyte (intestinal epithelial cell) by a variety of AA transporters that are specific for cationic (basic) AA, neutral AA, and anionic (acidic) AA. Small peptides are absorbed into enterocytes by the PEPT1 transporter. Inside enterocytes peptides are hydrolyzed, and the resulting amino acids are released together with those absorbed by AA transporters into blood via multiple, basolateral, AA transporters. Hydrolysis-resistant peptides, however, are transported out of the cells by a basolateral peptide transporter that has not been identified molecularly. CLASS Organismal Systems; Digestive system PATHWAY_MAP ko04974 Protein digestion and absorption DBLINKS GO: 0044256 0050892 ORTHOLOGY K06002 pepsin A [EC:3.4.23.1] K01312 trypsin [EC:3.4.21.4] K01310 chymotrypsin [EC:3.4.21.1] K09632 chymotrypsin-like protease [EC:3.4.21.-] K01346 pancreatic elastase II [EC:3.4.21.71] K01345 pancreatic endopeptidase E [EC:3.4.21.70] K08779 carboxypeptidase A1 [EC:3.4.17.1] K01298 carboxypeptidase A2 [EC:3.4.17.15] K08780 carboxypeptidase A3 [EC:3.4.17.1] K01291 carboxypeptidase B [EC:3.4.17.2] K01300 carboxypeptidase B2 [EC:3.4.17.20] K12040 solute carrier family 9 (sodium/hydrogen exchanger), member 3 K14206 solute carrier family 15 (oligopeptide transporter), member 1 K01539 sodium/potassium-transporting ATPase subunit alpha [EC:7.2.2.13] K01540 sodium/potassium-transporting ATPase subunit beta K01538 sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2) K04945 potassium intermediate/small conductance calcium-activated channel subfamily N member 4 K04916 potassium channel subfamily K member 5 K04897 potassium voltage-gated channel Isk-related subfamily E member 3 K04926 potassium voltage-gated channel KQT-like subfamily member 1 K05006 potassium inwardly-rectifying channel subfamily J member 13 K14207 solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 2 K01389 neprilysin [EC:3.4.24.11] K01395 meprin A [EC:3.4.24.18] K08606 meprin B [EC:3.4.24.63] K09708 angiotensin-converting enzyme 2 [EC:3.4.17.23] K01285 lysosomal Pro-X carboxypeptidase [EC:3.4.16.2] K01278 dipeptidyl-peptidase 4 [EC:3.4.14.5] K14208 Xaa-Pro aminopeptidase 2 [EC:3.4.11.9] K05612 solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter), member 1 K05616 solute carrier family 1 (neutral amino acid transporter), member 5 K05849 solute carrier family 8 (sodium/calcium exchanger) K05334 solute carrier family 6 (neurotransmitter transporter) member 19 K06519 solute carrier family 3, member 2 K13781 solute carrier family 7 (L-type amino acid transporter), member 8 K14209 solute carrier family 36 (proton-coupled amino acid transporter) K08187 MFS transporter, MCT family, solute carrier family 16 (monocarboxylic acid transporters), member 10 K14210 solute carrier family 3 (neutral and basic amino acid transporter), member 1 K13868 solute carrier family 7 (L-type amino acid transporter), member 9/15 K13867 solute carrier family 7 (L-type amino acid transporter), member 7 K14211 elastin K06236 collagen type I alpha K19719 collagen type II alpha K19720 collagen type III alpha K06237 collagen type IV alpha K19721 collagen type V/XI/XXIV/XXVII, alpha K06238 collagen type VI alpha K16628 collagen type VII alpha K23455 collagen type VIII alpha K08131 collagen type IX alpha K19479 collagen type X alpha K08132 collagen type XII alpha K16617 collagen type XIII alpha K08133 collagen type XIV alpha K08135 collagen type XV alpha K24339 collagen type XVI alpha K07603 collagen type XVII alpha K06823 collagen type XVIII alpha K24340 collagen type XIX alpha K24357 collagen type XX alpha K16629 collagen type XXI alpha K16630 collagen type XXII alpha K24355 collagen type XXIII alpha K24356 collagen type XXV alpha K24358 collagen type XXVI alpha (EMI domain-containing protein 2) K23619 collagen type XXVIII alpha COMPOUND C00011 CO2 C00014 Ammonia C00025 L-Glutamate C00033 Acetate C00037 Glycine C00041 L-Alanine C00047 L-Lysine C00049 L-Aspartate C00062 L-Arginine C00064 L-Glutamine C00065 L-Serine C00073 L-Methionine C00076 Calcium cation C00078 L-Tryptophan C00079 L-Phenylalanine C00080 H+ C00082 L-Tyrosine C00097 L-Cysteine C00099 beta-Alanine C00123 L-Leucine C00134 Putrescine C00135 L-Histidine C00146 Phenol C00148 L-Proline C00152 L-Asparagine C00163 Propanoate C00183 L-Valine C00188 L-Threonine C00238 Potassium cation C00246 Butanoic acid C00282 Hydrogen C00388 Histamine C00407 L-Isoleucine C00463 Indole C00483 Tyramine C00491 L-Cystine C01327 Hydrochloric acid C01330 Sodium cation C01438 Methane C01468 4-Cresol C01672 Cadaverine C01746 Piperidine C02632 2-Methylpropanoate C05996 Branched chain fatty acid C08262 3-Methylbutanoic acid C16138 L-Pyrrolysine C18319 2-Methylbutyrate REFERENCE PMID:18195088 AUTHORS Broer S TITLE Amino acid transport across mammalian intestinal and renal epithelia. JOURNAL Physiol Rev 88:249-86 (2008) DOI:10.1152/physrev.00018.2006 REFERENCE PMID:15772300 AUTHORS Palacin M, Nunes V, Font-Llitjos M, Jimenez-Vidal M, Fort J, Gasol E, Pineda M, Feliubadalo L, Chillaron J, Zorzano A TITLE The genetics of heteromeric amino acid transporters. JOURNAL Physiology (Bethesda) 20:112-24 (2005) DOI:10.1152/physiol.00051.2004 REFERENCE PMID:20522896 AUTHORS Goodman BE TITLE Insights into digestion and absorption of major nutrients in humans. JOURNAL Adv Physiol Educ 34:44-53 (2010) DOI:10.1152/advan.00094.2009 REFERENCE PMID:11546643 AUTHORS Wagner CA, Lang F, Broer S TITLE Function and structure of heterodimeric amino acid transporters. JOURNAL Am J Physiol Cell Physiol 281:C1077-93 (2001) DOI:10.1152/ajpcell.2001.281.4.C1077 REFERENCE PMID:18400692 AUTHORS Broer S TITLE Apical transporters for neutral amino acids: physiology and pathophysiology. JOURNAL Physiology (Bethesda) 23:95-103 (2008) DOI:10.1152/physiol.00045.2007 REFERENCE PMID:9687539 AUTHORS Wu G TITLE Intestinal mucosal amino acid catabolism. JOURNAL J Nutr 128:1249-52 (1998) DOI:10.1093/jn/128.8.1249 REFERENCE PMID:14977407 AUTHORS Daniel H TITLE Molecular and integrative physiology of intestinal peptide transport. JOURNAL Annu Rev Physiol 66:361-84 (2004) DOI:10.1146/annurev.physiol.66.032102.144149 REFERENCE PMID:12237156 AUTHORS Rubio-Aliaga I, Daniel H TITLE Mammalian peptide transporters as targets for drug delivery. JOURNAL Trends Pharmacol Sci 23:434-40 (2002) DOI:10.1016/S0165-6147(02)02072-2 REFERENCE PMID:7937532 AUTHORS Bai JP TITLE Distribution of brush-border membrane peptidases along the rat intestine. JOURNAL Pharm Res 11:897-900 (1994) DOI:10.1023/a:1018946228432 REFERENCE PMID:12583961 AUTHORS Guarner F, Malagelada JR TITLE Gut flora in health and disease. JOURNAL Lancet 361:512-9 (2003) DOI:10.1016/S0140-6736(03)12489-0 REFERENCE PMID:16887608 AUTHORS Smith EA, Macfarlane GT TITLE Dissimilatory amino Acid metabolism in human colonic bacteria. JOURNAL Anaerobe 3:327-37 (1997) DOI:10.1006/anae.1997.0121 REFERENCE PMID:20093818 AUTHORS Schepers E, Glorieux G, Vanholder R TITLE The gut: the forgotten organ in uremia? JOURNAL Blood Purif 29:130-6 (2010) DOI:10.1159/000245639 REFERENCE AUTHORS John H.Cummings TITLE The large intestine in nutrition and disease JOURNAL Institut Danone REFERENCE PMID:18626068 AUTHORS Heitzmann D, Warth R TITLE Physiology and pathophysiology of potassium channels in gastrointestinal epithelia. JOURNAL Physiol Rev 88:1119-82 (2008) DOI:10.1152/physrev.00020.2007 REL_PATHWAY ko00250 Alanine, aspartate and glutamate metabolism ko00280 Valine, leucine and isoleucine degradation ko00350 Tyrosine metabolism ko00380 Tryptophan metabolism ko04530 Tight junction ko04971 Gastric acid secretion ko04972 Pancreatic secretion ///