MetaCyc Enzyme: dehydropeptidase I

Gene: DPEP1 Accession Number: G-7621 (MetaCyc)

Synonyms: renal dipeptidase, RDP

Species: Rattus norvegicus

Subunit composition of dehydropeptidase I = [DPEP1]2
         dehydropeptidase I subunit = DPEP1

Several enzymes have been implicated in the hydrolysis of the cysteinyl-glycine dipeptide. Semenza [Semenza57] reported the isolation of such an enzyme from hog kidney. That enzyme was membrane bound, or at least enriched in membrane fractions. Two other peptidases with the same activity were isolated, and found to be membrane proteins as well; aminopeptidase M (EC [Rankin80] and dehydropeptidase I (EC [Hirota85]. The highest activities of these membrane-bound enzymes was found in kidney, intestine, and lung.

Unlike the above mentioned tissues, it was shown that in rat and ginea pig livers over 90% of the activity is found in the cytosolic fraction. Joesch et al [Josch03] have shown that this activity correlates with the cytosolic leucyl aminopeptidase (EC

Gene Citations: [Rached90]

Molecular Weight of Polypeptide: 44.7 kD (from nucleotide sequence), 78 kD (experimental) [Hirota85 ]

Molecular Weight of Multimer: 148 kD (experimental) [Hirota85]

Unification Links: ModBase:P22412 , Protein Model Portal:P22412 , SMR:P22412 , Swiss-Model:P22412 , UniProt:P22412

Relationship Links: Entrez-Nucleotide:PART-OF:X53730 , InterPro:IN-FAMILY:IPR000180 , InterPro:IN-FAMILY:IPR008257 , InterPro:IN-FAMILY:IPR028536 , Panther:IN-FAMILY:PTHR10443 , Panther:IN-FAMILY:PTHR10443:SF17 , Pfam:IN-FAMILY:PF01244 , Prosite:IN-FAMILY:PS00869 , Prosite:IN-FAMILY:PS51365

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Instance reaction of [a dipeptide + H2O → 2 amino acids] (
i1: L-glutamyl-L-glutamate + H2O → 2 L-glutamate (

MultiFun Terms: cell processes protection detoxification
metabolism degradation of macromolecules proteins/peptides/glycopeptides

Enzymatic reaction of: dehydropeptidase

EC Number:

a dipeptide + H2O <=> 2 amino acids

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Dehydropeptidase I has been purified from pig kidney to homogeneity [Hirota85] and is implicated in the renal metabolism of glutathione and its conjugates.. It hydrolyzes a wide range of dipeptides, including L-leucyl-L-leucine dipeptide and L-cysteinyl-glycine. It also converts leukotriene D4 to leukotriene E4, and may play an important role in the regulation of leukotriene activity.

Inhibitors (Unknown Mechanism): cilastatin [Hirota85]


Hirota85: Hirota T, Nishikawa Y, Takahagi H, Igarashi T, Kitagawa H (1985). "Simultaneous purification and properties of dehydropeptidase-I and aminopeptidase-M from rat kidney." Res Commun Chem Pathol Pharmacol 49(3);435-45. PMID: 2865778

Josch03: Josch C, Klotz LO, Sies H (2003). "Identification of cytosolic leucyl aminopeptidase (EC as the major cysteinylglycine-hydrolysing activity in rat liver." Biol Chem 384(2);213-8. PMID: 12675513

Rached90: Rached E, Hooper NM, James P, Semenza G, Turner AJ, Mantei N (1990). "cDNA cloning and expression in Xenopus laevis oocytes of pig renal dipeptidase, a glycosyl-phosphatidylinositol-anchored ectoenzyme." Biochem J 271(3);755-60. PMID: 2173907

Rankin80: Rankin BB, McIntyre TM, Curthoys NP (1980). "Brush border membrane hydrolysis of S-benzyl-cysteine-p-nitroanilide, and activity of aminopeptidase M." Biochem Biophys Res Commun 96(3);991-6. PMID: 6108111

Semenza57: Semenza, G. (1957). "Chromatographic purification of cysteinyl-glycinase." Biochim Biophys Acta 24(2);401-13. PMID: 13436444

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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