Dipeptidyl carboxypeptidases

Diamine oxidase (pig kidney, human pregnancy plasma, pea seedlings) 261 Dihydrolipoyl transacetylase (Escherichia coli)[27] Dipeptidyl carboxypeptidase[281 DNA polymerase-a (human)1291... 

Reeves, P.G. 1990. Zinc deficiency and dipeptidyl carboxypeptidase activity. Comparative effects on epididymis and testis of rats. Biol. Trace Elem. Res. 24 1-11. 

ACE is a rather nonspecific peptidase that can cleave C-terminal dipeptides from various peptides (dipeptidyl carboxypeptidase). As kininase 11, it contributes to the inactivation of kinins, such as bradykinin. ACE is also present in blood plasma however, enzyme localized in the luminal side of vascular endothelium is primarily responsible for the formation of angiotensin 11. The lung is rich in ACE, but kidneys, heart, and other organs also contain the enzyme. 

This zinc-dependent enzyme [EC 3.4.15.1] (also known as dipeptidyl carboxypeptidase I, dipeptidyl-dipeptidase A, kininase II, peptidase P, and carboxycathepsin) catalyzes the release of a C-terminal dipeptide at a neutral pH. The enzyme will also act on bradykinin. The presence of prolyl residues in angiotensin I and in bradykinin results in only single dipeptides being released due to the activity of this enzyme, a protein which belongs to the peptidase M2 family. The enzyme is a glycoprotein, generally membrane-bound, that is chloride ion-dependent. 

Ryan, J.W. 1988. Angiotensin-converting enzyme, dipeptidyl carboxypeptidase I, and its inhibitor. 

Metalloproteases include carboxypeptidase [1, 29, 30], ACE (a dipeptidyl carboxypeptidase) [13, 31] and a variety of matrix metalloproteases (matrixins or MMPs) [1, 32, 33]. ACE catalyzes the formation of the vasoconstrictive hormone angiotensin II from angiotensin I, some ACE inhibitors being important anti-hypertensive drugs [13, 31]. 

Cysteine proteases are so called because of a critical cysteine involved (together with an adjacent histidine) in the catalytic mechanism. Cysteine proteases include papain-related proteases, calpain-related proteases and the caspases. Papain-like cysteine proteases include the plant enzymes actinidin, aleurain, bromelain, caricain, chymopapain, ficin and papain and the lysosomal cathepsins B, C, H, K, L and S. Cathepsin C is multimeric (MW -200,000), but the other papain-related proteases are monomeric with MWs of about 20,000-35,000. While cathepsin C is a dipeptidyl aminopeptidase, the other enzymes are endopeptidases. Cathepsin B is an endopeptidase and a dipeptidyl carboxypeptidase. Cathepsin H is an endopeptidase and an aminopeptidase. In higher animals, cathepsin B generates peptides from antigens for presentation to T cells by the major histocompatibility... 

Angiotensin I converting enzyme is a dipeptidyl carboxypeptidase that cleaves angiotensin I to angiotensin II and the dipeptide histidyl-leucine (His-Leu). The enzyme is bound to the membrane of lung arterial endothelium and is involved in the renin-angiotensin system that regulates blood pressure and fluid balance. 

The dipeptidyl carboxypeptidase was prepared from rat lungs. A microsomal fraction was prepared and extracted with detergent (sodium deoxycho-late) and clarified by centrifugation. The supernatant solution was dialyzed against sodium phosphate, and the dialysate was stored frozen. 

Enkephalinase A (dipeptidyl carboxypeptidase) and enkephalinase B (dipep-tidyl aminopeptidase) are involved in the degradation of enkephalin, which has an opiate-like activity. Enkephalinase A cleaves methionine enkephalin (Tyr-Gly-Gly-Phe-Met) after the second glycine, whereas enkephalinase B cleaves after the first glycine. A postcolumn derivatization system is used to detect N-terminal tyrosine-containing peptides. 

Dipeptidyl carboxypeptidase A (EC 3.4.15.1 angiotensinconverting enzyme ACE kininase II) is a much-studied... 

Dipeptidyl carboxypeptidases remove the C-terminal dipeptide intact and therefore are analogous to the dipeptidyl aminopeptidases such as cathepsin C. One such enzyme, angiotensin-converting enzyme, is important biologically for converting angiotensin I into the hypertensive angiotensin II (see Section 9.3). This enzyme does not hydrolyse bonds of the type X—Pro but will hydrolyse Pro—X bonds. The use of dipeptidyl carboxypeptidases for sequence determination would probably increase if pure enzymes were readily available commercially. 

FIGURE 6.23 Interactions between ACE (a dipeptidyl carboxypeptidase) and a substrate O ft) or inhibitors (right). Source Adapted after Cushman et al. ... 

The prohormone Angiotensin I is then cleaved at the Phe8-His9 peptide bond by the relatively nonspecific ACE (also known as kininase II or dipeptidyl carboxypeptidase). ACE is a membrane-bound glycoprotein, found to be in the epithelial cells of pulmonary capillaries, the urogenital tract, the spleen, and the intestine. Incidentally, by removal of the terminal two amino acids from the carboxyl end of des-Asp-Angiotensin I, ACE can produce seven-membered peptide angiotensin III. The kininase responsible for the breakdown of bradykinin is now known to be identical to ACE. 

Converting enzyme is a dipeptidyl-carboxypeptidase that catalyses dipeptide separation from carboxylic terminal of a series of peptides. 

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