Background[1-3]
Inosine triphosphate pyrophosphatase antibody is a type of polyclonal antibody that can specifically bind to inosine triphosphate pyrophosphatase. It is mainly used in immunological experiments to detect inosine triphosphate pyrophosphatase.
Inosine triphosphate (ITP) is a normal component of cells and participates in many biochemical reactions. It is an intermediate product involved in the purine metabolism pathway and is present in the production of ATP and GTP. It contains an inosine nucleotide containing three phosphate groups esterified to a sugar moiety.
Inosine triphosphate pyrophosphatase
Pyrophosphatase is an anhydride hydrolase that acts on double phosphate bonds. It is an enzyme that catalyzes the conversion of one molecule of pyrophosphate into two molecules of phosphate ions. The function of pyrophosphatase is to play an important role in lipid metabolism (including lipid synthesis and breakdown), calcium absorption, bone formation and DNA synthesis, as well as other biochemical transformations.
Inosine trisphosphate pyrophosphatase (ITPase) is a cytosolic enzyme that belongs to the HAM1 NTPase family. ITPase hydrolyzes the non-canonical purine Kao antistatic nucleotides inosine triphosphate (ITP) and deoxyinosine triphosphate (dITP) into nucleotide monophosphates (IMP) and diphosphates. The ITPase enzyme acts as a homodimer and cannot differentiate between deoxy and ribose forms. ITPase may exclude non-canonical purines from the pool of RNA and DNA precursors, thereby preventing their incorporation into RNA and DNA and avoiding chromosomal damage. Defects in ITPase are thought to be hereditary and are characterized by excessive accumulation of ITP in red blood cells, white blood cells, and fibroblasts.
Apply[4][5]
Study on the relationship between TPMT and ITPA gene polymorphisms and adverse reactions caused by azathioprine in kidney transplant recipients
Thiopurine methyltransferase (TPMT) and inosine triphosphophosphate pyrophosphatase (ITPA) are both related to the metabolism of AZA. Since the genes controlling TPMT and ITPA have genetic polymorphisms, the metabolism of AZA in the population It shows obvious polymorphism, which makes the intensity and toxicity of different individual drugs also different. Therefore, in organ transplant patients, studying the relationship between TPMT and ITPA gene polymorphisms and adverse reactions caused by AZA will help to personalize AZA medication and avoid serious adverse reactions.
The study selected 155 kidney transplant recipients who were taking or had taken AZA as research subjects, and a new high-performance liquid chromatography (HPLC) fluorescence method was established to detect the TPMT activity of their red blood cells and determine the distribution of TPMT activity. The allele-specific PCR and restriction fragment length polymorphism (PCR-RFLP) methods were used to detect the gene mutation frequencies of TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. In addition, this study took healthy subjects as research subjects and examined the effects of commonly used drugs in kidney transplant recipients such as cyclosporine, hydrocortisone, and nifedipine on TPMT activity. On the other hand, this study established a new HPLC method to detect the ITPA activity of red blood cells in these 155 kidney transplant recipients and determine the distribution of ITPA activity. Real-time fluorescence quantitative PCR and PCR-RFLP methods were used to detect the gene mutation frequencies of ITPA 94C>A and IVS2+21A>C. On this basis, combined with the adverse reactions of these 155 kidney transplant recipients, the relationship between TPMT and ITPA activities and gene polymorphisms and adverse reactions caused by AZA was systematically analyzed.
The results showed that the TPMT activity range of 155 patients was 13.0468.25U, and the average activity was (36.00±12.32)U, showing a normal distribution. 30 patients (19.4%) showed moderate TPMT activity, and no patients with low TPMT activity or lack of enzyme activity were found. A total of 7 TPMT*3C mutation gene heterozygous individuals were found, with a mutation frequency of 2.26%. All 7 patients showed moderate TPMT activity, indicating that TPMT*3C gene mutation can lead to a reduction in TPMT activity.
In vitro, cyclosporine, hydrocortisone, captopril and allopurinol have weak inhibitory effects on TPMT activity. Nifedipine can significantly inhibit the activity of TPMT. The average IC50 value of the moderate activity group was (24.37±16.64) μg·mL-1, and the average IC50 value of the normal activity group was (11.81±10.03) μg·mL-1. 155 cases The ITPA activity range of kidney transplant recipients was 0191.2U, with an average of (96.1±37.1)U, showing a bimodal distribution.
