KEGG   PATHWAY: hsa04974Help
Entry
hsa04974                    Pathway                                

Name
Protein digestion and absorption - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Protein digestion and absorption
hsa04974

All organismsOrtholog table
Disease
H00843  
Hartnup disorder
H00899  
Lysinuric protein intolerance (LPI)
H00901  
Cystinuria
H00905  
Iminoglycinuria
H00911  
Dicarboxylic aminoaciduria
H00933  
Hereditary pancreatitis
H01304  
Hyperglycinuria
Drug
D05183  
Ulinastatin (JP16)
D06553  
Alogliptin benzoate (JAN/USAN)
D06578  
Denagliptin tosylate (USAN)
D06645  
Sitagliptin phosphate hydrate (JAN)
D07080  
Vildagliptin (JAN/USAN/INN)
D08516  
Sitagliptin (Prop.INN)
D08616  
Teneligliptin (INN)
D08631  
Carmegliptin (USAN/INN)
D08996  
Saxagliptin (INN)
D09326  
Carmegliptin dihydrochloride (USAN)
D09333  
Dutogliptin (USAN)
D09334  
Dutogliptin tartrate (USAN)
D09566  
Linagliptin (JAN/USAN/INN)
D09625  
Gosogliptin (USAN/INN)
D09753  
Saxagliptin hydrate (JAN/USAN)
D09756  
Teneligliptin hydrobromide hydrate (JAN)
D09780  
Anagliptin (JAN/INN)
D10178  
Trelagliptin (USAN)
D10179  
Trelagliptin succinate (JAN/USAN)
Other DBs
Organism
Homo sapiens (human) [GN:hsa]
Gene
5222  
PGA5; pepsinogen 5, group I (pepsinogen A) [KO:K06002] [EC:3.4.23.1]
643847  
PGA4; pepsinogen 4, group I (pepsinogen A) [KO:K06002] [EC:3.4.23.1]
643834  
PGA3; pepsinogen 3, group I (pepsinogen A) [KO:K06002] [EC:3.4.23.1]
5646  
PRSS3; protease, serine, 3 [KO:K01312] [EC:3.4.21.4]
5645  
PRSS2; protease, serine, 2 (trypsin 2) [KO:K01312] [EC:3.4.21.4]
5644  
PRSS1; protease, serine, 1 (trypsin 1) [KO:K01312] [EC:3.4.21.4]
1506  
CTRL; chymotrypsin-like [KO:K09632] [EC:3.4.21.-]
63036  
CELA2A; chymotrypsin-like elastase family, member 2A [KO:K01346] [EC:3.4.21.71]
51032  
CELA2B; chymotrypsin-like elastase family, member 2B [KO:K01346] [EC:3.4.21.71]
10136  
CELA3A; chymotrypsin-like elastase family, member 3A [KO:K01345] [EC:3.4.21.70]
23436  
CELA3B; chymotrypsin-like elastase family, member 3B [KO:K01345] [EC:3.4.21.70]
1357  
CPA1; carboxypeptidase A1 (pancreatic) [KO:K08779] [EC:3.4.17.1]
1358  
CPA2; carboxypeptidase A2 (pancreatic) [KO:K01298] [EC:3.4.17.15]
1359  
CPA3; carboxypeptidase A3 (mast cell) [KO:K08780] [EC:3.4.17.1]
1360  
CPB1; carboxypeptidase B1 (tissue) [KO:K01291] [EC:3.4.17.2]
1361  
CPB2; carboxypeptidase B2 (plasma) [KO:K01300] [EC:3.4.17.20]
6550  
SLC9A3; solute carrier family 9, subfamily A (NHE3, cation proton antiporter 3), member 3 [KO:K12040]
6564  
SLC15A1; solute carrier family 15 (oligopeptide transporter), member 1 [KO:K14206]
476  
ATP1A1; ATPase, Na+/K+ transporting, alpha 1 polypeptide [KO:K01539] [EC:3.6.3.9]
477  
ATP1A2; ATPase, Na+/K+ transporting, alpha 2 polypeptide [KO:K01539] [EC:3.6.3.9]
478  
ATP1A3; ATPase, Na+/K+ transporting, alpha 3 polypeptide [KO:K01539] [EC:3.6.3.9]
480  
ATP1A4; ATPase, Na+/K+ transporting, alpha 4 polypeptide [KO:K01539] [EC:3.6.3.9]
23439  
ATP1B4; ATPase, Na+/K+ transporting, beta 4 polypeptide [KO:K01540]
481  
ATP1B1; ATPase, Na+/K+ transporting, beta 1 polypeptide [KO:K01540]
482  
ATP1B2; ATPase, Na+/K+ transporting, beta 2 polypeptide [KO:K01540]
483  
ATP1B3; ATPase, Na+/K+ transporting, beta 3 polypeptide [KO:K01540]
486  
FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
3783  
KCNN4; potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 [KO:K04945]
8645  
KCNK5; potassium channel, subfamily K, member 5 [KO:K04916]
10008  
KCNE3; potassium voltage-gated channel, Isk-related family, member 3 [KO:K04897]
3784  
KCNQ1; potassium voltage-gated channel, KQT-like subfamily, member 1 [KO:K04926]
3769  
KCNJ13; potassium inwardly-rectifying channel, subfamily J, member 13 [KO:K05006]
54407  
SLC38A2; solute carrier family 38, member 2 [KO:K14207]
4311  
MME; membrane metallo-endopeptidase [KO:K01389] [EC:3.4.24.11]
4224  
MEP1A; meprin A, alpha (PABA peptide hydrolase) [KO:K01395] [EC:3.4.24.18]
4225  
MEP1B; meprin A, beta [KO:K08606] [EC:3.4.24.63]
59272  
ACE2; angiotensin I converting enzyme 2 [KO:K09708] [EC:3.4.17.23]
5547  
PRCP; prolylcarboxypeptidase (angiotensinase C) [KO:K01285] [EC:3.4.16.2]
1803  
DPP4; dipeptidyl-peptidase 4 [KO:K01278] [EC:3.4.14.5]
7512  
XPNPEP2; X-prolyl aminopeptidase (aminopeptidase P) 2, membrane-bound [KO:K14208] [EC:3.4.11.9]
6505  
SLC1A1; solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1 [KO:K05612]
6510  
SLC1A5; solute carrier family 1 (neutral amino acid transporter), member 5 [KO:K05616]
6546  
SLC8A1; solute carrier family 8 (sodium/calcium exchanger), member 1 [KO:K05849]
6543  
SLC8A2; solute carrier family 8 (sodium/calcium exchanger), member 2 [KO:K05849]
6547  
SLC8A3; solute carrier family 8 (sodium/calcium exchanger), member 3 [KO:K05849]
340024  
SLC6A19; solute carrier family 6 (neutral amino acid transporter), member 19 [KO:K05334]
6520  
SLC3A2; solute carrier family 3 (amino acid transporter heavy chain), member 2 [KO:K06519]
23428  
SLC7A8; solute carrier family 7 (amino acid transporter light chain, L system), member 8 [KO:K13781]
117247  
SLC16A10; solute carrier family 16 (aromatic amino acid transporter), member 10 [KO:K08187]
6519  
SLC3A1; solute carrier family 3 (amino acid transporter heavy chain), member 1 [KO:K14210]
11136  
SLC7A9; solute carrier family 7 (amino acid transporter light chain, bo,+ system), member 9 [KO:K13868]
9056  
SLC7A7; solute carrier family 7 (amino acid transporter light chain, y+L system), member 7 [KO:K13867]
2006  
ELN; elastin [KO:K14211]
1277  
COL1A1; collagen, type I, alpha 1 [KO:K06236]
1278  
COL1A2; collagen, type I, alpha 2 [KO:K06236]
1280  
COL2A1; collagen, type II, alpha 1 [KO:K06236]
1281  
COL3A1; collagen, type III, alpha 1 [KO:K06236]
1289  
COL5A1; collagen, type V, alpha 1 [KO:K06236]
1290  
COL5A2; collagen, type V, alpha 2 [KO:K06236]
1301  
COL11A1; collagen, type XI, alpha 1 [KO:K06236]
1302  
COL11A2; collagen, type XI, alpha 2 [KO:K06236]
50509  
COL5A3; collagen, type V, alpha 3 [KO:K06236]
255631  
COL24A1; collagen, type XXIV, alpha 1 [KO:K06236]
85301  
COL27A1; collagen, type XXVII, alpha 1 [KO:K06236]
1284  
COL4A2; collagen, type IV, alpha 2 [KO:K06237]
1286  
COL4A4; collagen, type IV, alpha 4 [KO:K06237]
1288  
COL4A6; collagen, type IV, alpha 6 [KO:K06237]
1282  
COL4A1; collagen, type IV, alpha 1 [KO:K06237]
1287  
COL4A5; collagen, type IV, alpha 5 [KO:K06237]
1285  
COL4A3; collagen, type IV, alpha 3 (Goodpasture antigen) [KO:K06237]
1291  
COL6A1; collagen, type VI, alpha 1 [KO:K06238]
1292  
COL6A2; collagen, type VI, alpha 2 [KO:K06238]
1293  
COL6A3; collagen, type VI, alpha 3 [KO:K06238]
131873  
COL6A6; collagen, type VI, alpha 6 [KO:K06238]
256076  
COL6A5; collagen, type VI, alpha 5 [KO:K06238]
1294  
COL7A1; collagen, type VII, alpha 1 [KO:K16628]
1297  
COL9A1; collagen, type IX, alpha 1 [KO:K08131]
1298  
COL9A2; collagen, type IX, alpha 2 [KO:K08131]
1299  
COL9A3; collagen, type IX, alpha 3 [KO:K08131]
1303  
COL12A1; collagen, type XII, alpha 1 [KO:K08132]
1305  
COL13A1; collagen, type XIII, alpha 1 [KO:K16617]
7373  
COL14A1; collagen, type XIV, alpha 1 [KO:K08133]
1306  
COL15A1; collagen, type XV, alpha 1 [KO:K08135]
1308  
COL17A1; collagen, type XVII, alpha 1 [KO:K07603]
80781  
COL18A1; collagen, type XVIII, alpha 1 [KO:K06823]
81578  
COL21A1; collagen, type XXI, alpha 1 [KO:K16629]
169044  
COL22A1; collagen, type XXII, alpha 1 [KO:K16630]
1504  
CTRB1; chymotrypsinogen B1 [KO:K01310] [EC:3.4.21.1]
206358  
SLC36A1; solute carrier family 36 (proton/amino acid symporter), member 1 [KO:K14209]
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
  Authors
Broer S
  Title
Amino acid transport across mammalian intestinal and renal epithelia.
  Journal
Physiol Rev 88:249-86 (2008)
Reference
  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)
Reference
  Authors
Goodman BE
  Title
Insights into digestion and absorption of major nutrients in humans.
  Journal
Adv Physiol Educ 34:44-53 (2010)
Reference
  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)
Reference
  Authors
Broer S
  Title
Apical transporters for neutral amino acids: physiology and pathophysiology.
  Journal
Physiology (Bethesda) 23:95-103 (2008)
Reference
PMID:9687539
  Authors
Wu G
  Title
Intestinal mucosal amino acid catabolism.
  Journal
J Nutr 128:1249-52 (1998)
Reference
  Authors
Daniel H
  Title
Molecular and integrative physiology of intestinal peptide transport.
  Journal
Annu Rev Physiol 66:361-84 (2004)
Reference
  Authors
Rubio-Aliaga I, Daniel H
  Title
Mammalian peptide transporters as targets for drug delivery.
  Journal
Trends Pharmacol Sci 23:434-40 (2002)
Reference
PMID:7937532
  Authors
Bai JP
  Title
Distribution of brush-border membrane peptidases along the rat intestine.
  Journal
Pharm Res 11:897-900 (1994)
Reference
  Authors
Guarner F, Malagelada JR
  Title
Gut flora in health and disease.
  Journal
Lancet 361:512-9 (2003)
Reference
  Authors
Smith EA, Macfarlane GT
  Title
Dissimilatory amino Acid metabolism in human colonic bacteria.
  Journal
Anaerobe 3:327-37 (1997)
Reference
  Authors
Schepers E, Glorieux G, Vanholder R
  Title
The gut: the forgotten organ in uremia?
  Journal
Blood Purif 29:130-6 (2010)
Reference
  Authors
John H.Cummings
  Title
The large intestine in nutrition and disease
  Journal
Institut Danone
Reference
  Authors
Heitzmann D, Warth R
  Title
Physiology and pathophysiology of potassium channels in gastrointestinal epithelia.
  Journal
Physiol Rev 88:1119-82 (2008)
KO pathway
 

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