Creatininase is a member of the urease-related amidohydrolases, the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically in cyclic amides. The systematic name of this enzyme class is creatinine amidohydrolase. This enzyme is also called creatinine hydrolase. This enzyme participates in arginine and proline metabolism. The content of creatininase is mostly skeletal muscle, cardiac muscle and smooth muscle, followed by brain tissue, and less content in the gastrointestinal tract, lung and kidney. Creatininase is mainly present in the cytoplasm and mitochondria, and it is an important kinase that is directly related to intracellular energy movement, muscle contraction, and ATP regeneration. Creatininase activity assay can be used for the diagnosis of skeletal muscle disease and myocardial disease.
Figure 1. Protein structure of creatininase.
Detection
The measurement of creatinine is difficult. The current commonly used methods are mass spectrometry (isotopic dilution mass spectrometry), high performance liquid chromatography, liquid chromatography-mass spectrometry and antibody detection (ELISA), these methods generally require expensive instruments, such as mass spectrometry, liquid chromatography Instruments or microplate readers, as well as systematically trained analytical chemistry operators, greatly increase the economic and time costs of creatinine measurement and the application of creatinine measurement in remote areas. Mass spectrometry is to artificially add creatinine containing a certain isotope (such as O-18) to the sample and analyze the sample by mass spectrometry. The concentration of creatinine can be calculated by comparing the abundance of O-18 and the abundance of O-18 in nature in the mass spectrometry results. The artificially added creatinine can be strictly controlled. As an internal calibration, this method can effectively reduce the error. According to the latest research, the low concentration of creatinine obtained by mass spectrometry will cause a series of clinical problems, and the US FDA has also begun to consider new creatinine detection methods. Liquid chromatography is the use of high-performance liquid chromatography on the basis of mass spectrometry to purify samples and detect them with mass spectrometry. Mass spectrometry and liquid chromatography cannot be automated, the operation is complicated, and the analysis team is required to operate and maintain the instrument. The ELISA method requires an expensive microplate reader. Although its sensitivity is extremely high, the selectivity is poor and often overestimating the concentration of creatinine leads to overdose or inadequate clinical medication.
Clinical significance
1. Increase
(1) Physiological increase: ①After exercise, creatininase can be significantly increased, and the more vigorous and longer the exercise, the more obvious the increase in creatininase. ② Serum creatininase activity in delivery and neonates is higher than normal. ③Some treatments and diagnostic measures, such as the installation of artificial cardiac pacemakers, electrical shock, radiation therapy, cardiac compression, cardiac catheterization, and urinary system examination, can increase the activity of serum creatininase. ④Men have large muscle capacity, and serum creatininase activity is higher than women. ⑤ Intramuscular injection of certain drugs (such as anesthetics, painkillers, antibiotics, dexamethasone, etc.) can cause increased serum creatininase activity. ⑥ Oral administration of certain drugs, such as clofibrate, can increase serum creatininase activity.
(2) Pathological increase: myocardial infarction, viral myocarditis, dermatomyositis, muscular dystrophy, pericarditis, cerebrovascular accident, etc.
2. Lower
Hyperthyroidism.
Reference
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Kha and Wolfgang W. A highly sensitive amperometric creatinine sensor. Analytica Chimica Acta,1997,351: 151-158.