Angiotensin Converting Enzyme

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Angiotensin-converting enzyme (ACE) is also known as kininase II or peptidyl-carboxypeptidase. It is a vascular endothelial cell membrane-binding enzyme, which is converted from the C-terminus of the peptide by cutting the amino acid into two sections, which can hydrolyze the C-terminus of the peptide chain. ACE is widely distributed in various tissues of the human body, and the content of epididymis, testis and lung is abundant. Among them, ACE activity of lung capillary endothelial cells is the highest. It attaches to the surface of endothelial cells and can be divided into the blood circulation.

Figure 1. Protein structure of angiotensin-converting enzyme (ACE).

Functions

• Catalyze the conversion of angiotensin I to angiotensin II;
• Inactivate bradykinin.
• Because of these two functions, angiotensin converting enzyme has become an ideal target for the treatment of hypertension, heart failure, diabetes and hypertension and other diseases. Angiotensin converting enzyme inhibitors can reduce the production of angiotensin II and increase the activity of bradykinin.
• In addition, ACE can also catalyze the conversion of angiotensin to angiotensin.
• ACE test results in lower results in lung cancer patients.

Mechanism

ACE is a zinc metalloprotease, and zinc ion is very important for its activity, because it directly participates in the catalysis of peptide hydrolysis. Therefore, ACE can be inhibited by metal chelating agents. It was found that E384 residue has a dual function. First, it serves as the general basis for nucleophiles to activate water. Then it acts as a general acid to cleave the C-N bond. The function of chloride ion is very complicated and controversial. The activation of anions by chloride is a characteristic of ACE. Experiments have determined that the activation of chloride on hydrolysis is highly dependent on the substrate. Although it increases the rate of hydrolysis, for example. Hip-His-Leu inhibits the hydrolysis of Hip-Ala-Pro and other substrates. Under physiological conditions, the enzyme reaches about 60% of its maximum activity on angiotensin I, while reaching its full activity on bradykinin. Therefore, it is assumed that the function of anion activation in ACE can provide higher substrate specificity. Other theories suggest that chloride can simply stabilize the overall structure of the enzyme.

Clinical significance

Serum ACE determination is mainly used for the diagnosis of lung diseases, and it also has certain value for the diagnosis and treatment of other system diseases. 　

1. Lung disease

The majority of patients with sarcoidosis have increased serum ACE activity, and the positive rate and amplitude are related to the disease activity and the extent of the lesion. Pulmonary tuberculosis can also be elevated, while serum ACEs such as asthma attacks, acute cardiogenic pulmonary edema, chronic obstructive pulmonary disease, spontaneous pneumothorax, pulmonary fibrosis, adult respiratory distress syndrome, etc. all have varying degrees of decline. 　

2. Liver disease

The ACE activity of most patients with liver disease is increased, and the increasing amplitude is in order of cirrhosis, acute hepatitis, and chronic hepatitis.

3. Thyroid disease

The ACE activity of patients with hyperthyroidism is significantly higher than that of other thyroid diseases, and the level of enzyme activity is positively correlated with the content of T3 and T4.

4. Other

Diabetes, iritis, immunoblastic sarcoma, etc., serum ACE increased; hypertension, colitis, etc. decreased.

References

1. Skeggs LT.; et al. The preparation and function of the hypertensin-converting enzyme. The Journal of Experimental Medicine. 1956, 103 (3): 295–9.
2. Natesh R.; et al. Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature. 2003, 421 (6922): 551–4.