NEW ASSAY FOR ANGIOTENSIN CONVERTING ENZYME (ACE)

As of January 5, 1996, a new, more precise assay for angiotensin converting enzyme (ACE) was introduced. The new assay uses a more sensitive substrate analog, N-[3-(2-furyl) acryloyl]-L-phenylalanylglycylglycine (FAPGG) (1, 2), in place of the old substrate, Hippuryl-L-his-L-Leu (HHL). The method involves hydrolysis of FAPGG to N-[3-(2-furyl)acryloyl]-L-phenylalanine (FAP) and gly-cylglycine. The release of FAP is monitored spectrophotometrically. The reference range for the new assay is 40-140 U/L. Because FAPGG is a better substrate than HHL, the new reference range is considerably higher than the old one of 20-48 U/L. The test is performed once a week (on Friday) in the Chemistry Laboratory in the Department of Laboratory Medicine at YNHH.

Angiotensin-converting enzyme is a halide-activated metallopeptidase responsible for the in vivo conversion of Angiotensin I to the potent vasoconstrictor, Angiotensin II. ACE further maintains vascular tension by inactivating the vasodilator, bradykinin. It was first noted by Lieberman (3) that patients with sarcoidosis had an increased activity of circulating ACE. The serum ACE assay is useful in differentiating sarcoidosis from other granulomatous diseases (4, 5). While almost all serum ACE in healthy persons is the result of release from endothelial cells, the excess ACE in patients with sarcoidosis appears to be produced by macrophages in the sarcoid granulomata. When underlying endothelial production of ACE is low, the ACE released by the patient's macrophages may not be sufficient to elevate the total value above the reference range. Accordingly, the predictive value of a negative test is only 70-80% (4). One study (6) showed patients with sarcoidosis had ACE activity of 220+48 U/L, while in normal adults activity was 100+35 U/L. Elevation of ACE has been observed in patients with other diseases, such as liver disease, hyperthyroidism, AIDS, diabetes, fungal infections and diseases with endothelial dysfunction (4,5). ACE activity may be used to follow the clinical course of sarcoidosis and to monitor the response to therapy (4). It should be noted that measurements of ACE activity are not useful in following the treatment of hypertension with ACE inhibitors.

Blood for this test should be collected in a heparinized (green top) tube and sent to Chemistry immediately. One milliliter of plasma is required. Serum (red top) is also acceptable. Blood anticoagulated with EDTA (purple top) cannot be used, because EDTA complexes the zinc ion in the active site and inactivates the ACE enzyme. The FDA has approved this method for serum and plasma, both of which yield the same result. If you have any questions regarding this test, please contact the Lab Medicine resident at 5-2444.

References

1. Harjanne A. Automated kinetic determination of angiotensin-converting enzyme in serum. Clin Chem 1984;30:901-902.
2. Buttery JE, Stuart S. Assessment and optimization of kinetic methods for angiotensin-converting enzyme in plasma. Clin Chem 1993;39:312-316
3. Lieberman J. Elevation of serum angiotensin-converting enzyme (ACE) level in sarcoidosis. Am J Med 1975;59: 365-372.
4. Beneteau-Burnat B, Baudin B. Angiotensin-converting enzyme: clinical applications and laboratory investigation on serum and other biological fluids. Crit Rev Clin Lab Sci 1991;28:337-356.
5. Allen RK. A review of angiotensin converting enzyme in health and disease. Sarcoidosis 1991;8:95-100.
6. Beneteau, et al. Automated kinetic assay of angiotensin-converting enzyme in serum. Clin Chem 1986;32:884-886.

Peiguo Chu, M.D., Ph.D.; Herbert Malkus, Ph.D.; Petrie Rainey, M.D., Ph.D.