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
09150 Organismal Systems; 09154 Digestive system
BRITE hierarchy
Pathway map
hsa04974  Protein digestion and absorption
hsa04974

Ortholog 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 (JP17)
D06553  Alogliptin benzoate (JAN/USAN)
D06578  Denagliptin tosylate (USAN)
D06645  Sitagliptin phosphate (USAN)
D07080  Vildagliptin (JAN/USAN/INN)
D08464  Racecadotril (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)
D10262  Saxagliptin hydrochloride
D10317  Omarigliptin (JAN/USAN/INN)
D10502  Gemigliptin (prop.INN)
D11023  Evogliptin (INN)
Other DBs
BSID: 172847
GO: 0044256 0050892
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; serine protease 3 [KO:K01312] [EC:3.4.21.4]
5645  PRSS2; serine protease 2 [KO:K01312] [EC:3.4.21.4]
5644  PRSS1; serine protease 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 [KO:K08779] [EC:3.4.17.1]
1358  CPA2; carboxypeptidase A2 [KO:K01298] [EC:3.4.17.15]
1359  CPA3; carboxypeptidase A3 [KO:K08780] [EC:3.4.17.1]
1360  CPB1; carboxypeptidase B1 [KO:K01291] [EC:3.4.17.2]
1361  CPB2; carboxypeptidase B2 [KO:K01300] [EC:3.4.17.20]
6550  SLC9A3; solute carrier family 9 member A3 [KO:K12040]
6564  SLC15A1; solute carrier family 15 member 1 [KO:K14206]
476  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:3.6.3.9]
477  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:3.6.3.9]
478  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:3.6.3.9]
480  ATP1A4; ATPase Na+/K+ transporting subunit alpha 4 [KO:K01539] [EC:3.6.3.9]
23439  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
481  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
482  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
483  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
486  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
3783  KCNN4; potassium calcium-activated channel subfamily N member 4 [KO:K04945]
8645  KCNK5; potassium two pore domain channel subfamily K member 5 [KO:K04916]
10008  KCNE3; potassium voltage-gated channel subfamily E regulatory subunit 3 [KO:K04897]
3784  KCNQ1; potassium voltage-gated channel subfamily Q member 1 [KO:K04926]
3769  KCNJ13; potassium voltage-gated channel subfamily J member 13 [KO:K05006]
54407  SLC38A2; solute carrier family 38 member 2 [KO:K14207]
4311  MME; membrane metalloendopeptidase [KO:K01389] [EC:3.4.24.11]
4224  MEP1A; meprin A subunit alpha [KO:K01395] [EC:3.4.24.18]
4225  MEP1B; meprin A subunit 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 [KO:K01285] [EC:3.4.16.2]
1803  DPP4; dipeptidyl peptidase 4 [KO:K01278] [EC:3.4.14.5]
7512  XPNPEP2; X-prolyl aminopeptidase 2 [KO:K14208] [EC:3.4.11.9]
6505  SLC1A1; solute carrier family 1 member 1 [KO:K05612]
6510  SLC1A5; solute carrier family 1 member 5 [KO:K05616]
6546  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
6543  SLC8A2; solute carrier family 8 member A2 [KO:K05849]
6547  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
340024  SLC6A19; solute carrier family 6 member 19 [KO:K05334]
6520  SLC3A2; solute carrier family 3 member 2 [KO:K06519]
23428  SLC7A8; solute carrier family 7 member 8 [KO:K13781]
117247  SLC16A10; solute carrier family 16 member 10 [KO:K08187]
6519  SLC3A1; solute carrier family 3 member 1 [KO:K14210]
11136  SLC7A9; solute carrier family 7 member 9 [KO:K13868]
9056  SLC7A7; solute carrier family 7 member 7 [KO:K13867]
2006  ELN; elastin [KO:K14211]
1277  COL1A1; collagen type I alpha 1 chain [KO:K06236]
1278  COL1A2; collagen type I alpha 2 chain [KO:K06236]
1280  COL2A1; collagen type II alpha 1 chain [KO:K19719]
1281  COL3A1; collagen type III alpha 1 chain [KO:K19720]
1284  COL4A2; collagen type IV alpha 2 chain [KO:K06237]
1286  COL4A4; collagen type IV alpha 4 chain [KO:K06237]
1288  COL4A6; collagen type IV alpha 6 chain [KO:K06237]
1282  COL4A1; collagen type IV alpha 1 chain [KO:K06237]
1287  COL4A5; collagen type IV alpha 5 chain [KO:K06237]
1285  COL4A3; collagen type IV alpha 3 chain [KO:K06237]
1289  COL5A1; collagen type V alpha 1 chain [KO:K19721]
1290  COL5A2; collagen type V alpha 2 chain [KO:K19721]
50509  COL5A3; collagen type V alpha 3 chain [KO:K19721]
1301  COL11A1; collagen type XI alpha 1 chain [KO:K19721]
255631  COL24A1; collagen type XXIV alpha 1 chain [KO:K19721]
85301  COL27A1; collagen type XXVII alpha 1 chain [KO:K19721]
1302  COL11A2; collagen type XI alpha 2 chain [KO:K19721]
1291  COL6A1; collagen type VI alpha 1 chain [KO:K06238]
1292  COL6A2; collagen type VI alpha 2 chain [KO:K06238]
1293  COL6A3; collagen type VI alpha 3 chain [KO:K06238]
131873  COL6A6; collagen type VI alpha 6 chain [KO:K06238]
256076  COL6A5; collagen type VI alpha 5 chain [KO:K06238]
1294  COL7A1; collagen type VII alpha 1 chain [KO:K16628]
1297  COL9A1; collagen type IX alpha 1 chain [KO:K08131]
1298  COL9A2; collagen type IX alpha 2 chain [KO:K08131]
1299  COL9A3; collagen type IX alpha 3 chain [KO:K08131]
1300  COL10A1; collagen type X alpha 1 chain [KO:K19479]
1303  COL12A1; collagen type XII alpha 1 chain [KO:K08132]
1305  COL13A1; collagen type XIII alpha 1 chain [KO:K16617]
7373  COL14A1; collagen type XIV alpha 1 chain [KO:K08133]
1306  COL15A1; collagen type XV alpha 1 chain [KO:K08135]
1308  COL17A1; collagen type XVII alpha 1 chain [KO:K07603]
80781  COL18A1; collagen type XVIII alpha 1 chain [KO:K06823]
81578  COL21A1; collagen type XXI alpha 1 chain [KO:K16629]
169044  COL22A1; collagen type XXII alpha 1 chain [KO:K16630]
1504  CTRB1; chymotrypsinogen B1 [KO:K01310] [EC:3.4.21.1]
206358  SLC36A1; solute carrier family 36 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)
DOI:10.1152/physrev.00018.2006
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)
DOI:10.1152/physiol.00051.2004
Reference
  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
  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)
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)
Reference
  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
  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)
Reference
  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
  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
  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
  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
KO pathway
ko04974   

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