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HomeProduct name listEC 3.4.15.1

EC 3.4.15.1

Synonym(s):ACE;Peptidyl-dipeptidase A;Peptidyldipeptide Hydrolase

EC 3.4.15.1 Structural

What is EC 3.4.15.1?

Description

ACE possesses dual actions to convert Ang I to Ang II, and degrade bradykinin. The development of an ACE inhibitor was the first effective drug for hypertension caused by high renin activity. ACE2 was identified as the receptor for the SARS (severe acute respiratory syndrome) coronavirus, which caused an epidemic in 2002–2003. ACE was discovered in the mid-1950s through the observation that the dialysis of plasma and kidney extract with water and saline before incubation produced two separate pressor substances, Ang I and Ang II, respectively. It was discovered for a second time in 1966 during the characterization of a bradykinin (BK)-degrading enzyme from the kidney. This was named kininase II, which later was found to be the same enzyme as ACE. ACE2 was discovered in 2000 when two independent research groups cloned homologous ACE that could convert Ang I to Ang1–9 and yet also be captopril-insensitive.

The Uses of EC 3.4.15.1

Angiotensin converting enzyme from rabbit lung has been used:

  • for measuring inhibitory effect of egg white protein hydrolysates on ACE activity by high performance liquid chromatography (HPLC)
  • to measure the ACE inhibition by litchi pericarp and cooked chicken breast using hippuryl-L-histidyl-L-leucine (HHL) as substrate by reverse phase-HPLC (RP-HPLC)3 and HPLC respectively
  • in releasing GPI anchored protein in vitro in few cell lines like HeLa, HEK293 and in vivo in mice sperm.

General Description

The angiotensin-converting enzyme (ACE) is a dipeptidyl-carboxypeptidase which exists in somatic and testicular isoforms with zinc binding motif HEXXH in their active site. ACE regulates blood pressure through renin-angiotensin system. ACE elevates blood pressure by converting angiotensin I to a key vasoconstrictor angiotensin II and inhibiting a potent vasodilator bradykinin. Inhibition of ACE is a targeted therapeutic strategy for high blood pressure. Several ACE synthetic inhibitory peptides available for clinical use include captopril, enalapril and lisinopril. Currently, developing inhibitory peptides from natural food sources, or phenolic compounds from plant sources to inhibit ACE is underway. ACE plays a critical role in fertilization by releasing the proteins anchored to glycosylphosphatidylinositol (GPI) in sperm membrane.

Biochem/physiol Actions

Removes C-terminal dipeptides from susceptible substrates, e.g., angiotensin I and bradykinin.

Clinical Use

ACE has been the target of hypertension control since the 1970s. ACE inhibitors are prescribed as the sole or combinational treatment for high blood pressure, for its dual effects of lowering Ang II and slowing down BK degradation. In human hypertensive patients, ACE2 levels are lower in both the kidney and heart compared to normotensive volunteers.

Purification Methods

Purify ACE by fractionation on DEAE-cellulose, Ca phosphate gel chromatography, elution from Sephadex G-200 and lectin affinity chromatography. The MW varied with glycosidation and is higher by gel filtration. It contains one atom of Zn/mol and has Km values for hydrolysis of hippurylhistidinylleucine and angiotensin I of 2.3 and 0.07 mM, and turnover of 15,430 and 792 mol/min/mol at 37o, respectively. The activity is inhibited by EDTA and increased amounts of Ca ions but required Ca ions. [Das & Soffer J Biol Chem 250 6762 1975, Reviewed by Ehlers & Riordan Biochemistry 28 5311 1989.]

Properties of EC 3.4.15.1

storage temp.  -20°C
form  lyophilized powder
color  Off-white to light yellow

Safety information for EC 3.4.15.1

Signal word Danger
Pictogram(s)
ghs
Health Hazard
GHS08
GHS Hazard Statements H334:Sensitisation, respiratory
Precautionary Statement Codes P261:Avoid breathing dust/fume/gas/mist/vapours/spray.
P284:Wear respiratory protection.
P501:Dispose of contents/container to..…

Computed Descriptors for EC 3.4.15.1

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