Angiotensin converting enzyme blood test
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Angiotensin Converting Enzyme Blood Test: Methods and Clinical Implications
Overview of Angiotensin Converting Enzyme (ACE) Blood Test
The angiotensin-converting enzyme (ACE) blood test is a diagnostic tool used to measure the level of ACE in the blood. ACE plays a crucial role in regulating blood pressure by converting angiotensin I to angiotensin II, a potent vasoconstrictor. Elevated levels of ACE can be indicative of certain medical conditions, such as sarcoidosis, and can also be influenced by genetic factors.
Colorimetric Assay for ACE Inhibitors
A colorimetric assay has been developed to measure ACE activity by detecting the release of hippuric acid (HA) from the substrate hippuryl-histidyl-leucine (HHL). This method involves mixing the released HA with pyridine and benzene sulfonyl chloride, resulting in a yellow color that can be measured at 410 nm. This assay is highly sensitive, with a detection limit of 1.46 x 10^(-7) M HA, and is comparable to the standard high-performance liquid chromatography (HPLC) method. It is particularly useful for high-throughput screening of ACE inhibitors, demonstrating precision, accuracy, and reproducibility.
Fluorimetric Assay for Serum ACE
Another method for measuring ACE in serum is a fluorimetric assay, which is simple, rapid, and highly sensitive. This assay quantifies the conversion of hippuryl-L-histidyl-L-leucine to hippurate and L-histidyl-L-leucine by forming a fluorescent adduct with ophthaldialdehyde. The fluorescence is measured at an excitation wavelength of 360 nm and an emission wavelength of 500 nm. This method has been shown to be useful in diagnosing and managing sarcoidosis, with a mean serum ACE value of 32.2 nmol/min/ml in normal subjects.
Radioassay for ACE Measurement
A radioassay technique measures ACE activity by tracking the release of 3H-labelled hippurate from p-[3H]benzoylglycylglycylglycine. The product is separated from the substrate using ethyl acetate extraction. This method provides results within 1.5 hours and is specific for ACE, although potential interference from other enzymes in abnormal sera must be considered.
Genetic Influence on Serum ACE Levels
The insertion/deletion (I/D) polymorphism in the ACE gene significantly impacts serum ACE levels. A study involving 80 healthy subjects found that this polymorphism accounts for 47% of the variance in serum ACE levels. Subjects with different ACE genotypes (homozygotes for the longer allele, heterozygotes, and homozygotes for the shorter allele) showed distinct serum ACE concentrations, highlighting the importance of considering genetic factors when interpreting ACE levels.
Genotype-Corrected Reference Values
To improve the accuracy of ACE blood tests, especially in the follow-up of sarcoidosis, genotype-specific reference values have been recommended. A study involving 159 healthy Caucasians established new normal ranges for serum ACE levels based on ACE genotypes. The highest serum ACE levels were observed in subjects with the D/D genotype, while the lowest were in those with the I/I genotype. These genotype-corrected reference values enhance the sensitivity and specificity of ACE tests.
Conclusion
The ACE blood test is a valuable diagnostic tool with various methods available for measuring ACE activity, including colorimetric, fluorimetric, and radioassay techniques. Genetic factors, particularly the I/D polymorphism in the ACE gene, play a significant role in determining serum ACE levels. Incorporating genotype-specific reference values can improve the diagnostic accuracy of ACE tests, particularly in managing conditions like sarcoidosis.
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