Angiotensin I converting enzyme ACE

Peptidyl-dipeptidase A (angiotensin-I converting enzyme, ACE, EC 3.4.15.1) plays a pivotal role in the control of blood pressure [80]. It has been established that its active site contains an essential Zn-atom that functions like that of carboxypeptidase A [2], ACE is inhibited by peptides having a proline or aromatic amino acid at the C-terminal position. These observations as well as the similarities with the active site of carboxypeptidase A have allowed a rational design of effective inhibitors of ACE (e.g., captopril (3.4) and enalapril (3.5)) used in the treatment of hypertension [81]. 

Vercruysse L, Smagghe G, Matsui T, Camp JV. (2008) Purification and identification of an angiotensin I-converting enzyme (ACE) inhibitory peptide from the gastrointestinal hydrolysate of the cotton leafworm, Spodoptera Littoralis. Process Biochem 43 900-904. 

Inhibitors of the angiotensin I-converting enzyme (ACE-inhibitors) have been introduced into cardiovascular medicine, in particular for the treatment of hypertension and congestive heart failure (CHE). 

Wijesekara, I. and Kim, S. K. (2010). Angiotensin-i-converting enzyme (ace) inhibitors from marine resources Prospects in the pharmaceutical industry. Mar. Drugs 8,1080-1093. 

Byun, H. G. and Kim, S. K. (2001). Purification and characterization of angiotensin I converting enzyme (ACE) inhibitory peptides from Alaska Pollack (Theragra chalcogramma) skin. Process Biochem. 36,1155-1162. 

Bougatef, A., Nedjar-Arroume, N., Ravallec-Ple, R., Leroy, Y., Guillochon, D., Barkia, A., and Nasri, M. (2008). Angiotensin I-converting enzyme (ACE) inhibitory activities of sardi-nelle (Sardinella aurita) by-products protein hydrolysates obtained by treatment with microbial and visceral fish serine proteases. Food Chem. Ill, 350-356. 

Hwang, J. S. (2010). Impact of processing on stability of angiotensin I-converting enzyme (ACE) inhibitory peptides obtained from tuna cooking juice. Food Res. Int. 43, 902-906. 

Angiotensin-I converting enzyme (ACE) controls blood pressure by catalyzing the hydrolysis of two amino acids (His-Leu) at the C-terminus of angiotensin-I to produce a vasoconstrictor, angiotensin-II. The enzyme can also hydrolyze a synthetic substrate, hippuryl-L-histidyl-L-leucine (HHL), to hippuric acid (HA). At four different concentrations of HHL solutions (pH 8.3), the initial rates of HA formation (pmolmin" ) are obtained as shown in Table P3.8. Several small peptides (e.g., Ile-Lys-Tyr) can reversibly inhibit the ACE activity. The reaction rates of HA formation in the presence of 1.5 and 2.5 pmoll of an inhibitory peptide (Ile-Lys-Tyr) are also given in the table. 

The angiotensin I-converting enzyme (ACE), designated peptidyl-dipeptidase A (E.C.3.4.15.1), is identical to the bradykinin-metabolizing enzyme kininase II (38). Its early history and initial characterizations have been reviewed (51-54). It was discovered by Skeggs and co-workers (55), and in their pioneering work they showed it to be inhibited by ethylene-diaminetetraacetic acid (EDTA) (37), to remove a dipeptide from the carboxyl terminus of angiotensin I (then called hypertensin I [56]) and to be activated by sodium chloride (55). The fact that ACE is a Zn2+-contain-ing peptidase was first reported by Das and Sofler in 1975 (57). 

Synthetic peptide inhibitors have been developed for a variety of proteases [199-204]. Peptide inhibitors of the metalloprotease angiotensin I converting enzyme (ACE) are of major importance as hypertensive agents [13, 31]. A variety of peptides derived from protease-catalyzed hydrolysis of com cc-zein [202-203] or of wheat germ protein [199, 204] inhibit ACE (Table 6). The most potent of such plant-derived ACE inhibitory peptides is Ile-Val-Tyr (IVY) (Ki 0.1 xM) [199, 204], Further plant-derived peptide ACE inhibitors include the tripeptide glutathione [73, 82], the glutathione -related peptide Y-L-glutamyl-(+)-allyl-L-cysteine sulphoxide [73, 82, 200, 201] and the tripeptide His-His-Leu (HHL) from fermented soybean [201] (Table 6). 

T-Kininogen (TK) (single chain glycoproteins Cystatin-like domains) Metalloproteases (MPRs) Angiotensin-I converting enzyme (ACE) Bradykinin inflammation, vascular regulation, vasodilation] 13.5C-D 13.5C... 

Lisinopril is an angiotensin I-converting enzyme (ACE) inhibitor. It competitively inhibits ACE, prevents angiotensin I conversion to angiotensin II, and is a potent vasoconstrictor that also stimnlates aldosterone secretion. Results are a decrease in sodinm and fluid retention, a decrease in BP, and increase in dinresis. It is indicated in the treatment of hypertension treatment of heart failure not responding to dinretics and digitalis and treatment of acute MI within 24 honrs in hemodynamically stable patients. 

The antihypertensive effect of tea leaf saponin (TLS) was examined in spontaneously hypertensive rats [187]. TLS reduced increase in blood pressure in a time and dose-dependent manner when it was administered orally to young animals for 5 days. Simple administration of TLS at 50 mg/kg p.o. showed a long lasting hypotensive effect which was as potent as that of enalapril at a dose of 3 mg/kg, p.o. TLS in an in vitro bioassay, didn t show inhibitory activity against angiotensin I converting enzyme (ACE I) (IC50> 10 mg/ml) [187]. 

The angiotensin I-converting enzyme (ACE) participates in regulating blood pressure in the renin-angiotensin system. The inhibitors such as captopril (Suetsuna and Chen, 2001) and enalapril (Sawayama et ah, 1990) have been used as antih)/pertensive drugs. The ACE-inhibitory activity of various source have studied, and it was found that some ACE-inhibitory peptides were produced by enzymatic digestion of various marine food proteins, including tuna muscle (Kohama et al., 1991 Qndetti, 1977), sardine muscle (Suetsima et al., 1991), dried bonito (Yokoyama et ah, 1992), dried-salted fish (Astawan et ah, 1995), fish sauce (Okamoto et al, 1995), and fish water-soluble protein (Wako et ah, 1999). 

Sheih, I. C., Fang, T. J., and Wu, T. K. (2009). Isolation and characterization of a novel angiotensin I-converting enzyme (ACE) inhibitory peptide from the algae protein waste. Food Chem. 115, 279-284. 

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