Synthesis and metabolism of purine nucleotides There are two ways to synthesize purine nucleotides in vivo, one is de novo synthesis, and the other is salvage synthesis, in which de novo synthesis is the main way.
Ab initio synthesis of 1. purine nucleotide
Liver is the main organ for de novo synthesis of purine nucleotides in vivo, followed by intestinal mucosa and purine nucleotide synthesis pathway.
Thymus. Purine nucleotides are synthesized in cytoplasm, and the raw materials include ribose phosphate, aspartic acid, glycine, glutamine, a carbon unit and CO2. The main reaction steps are divided into two stages: first, hypoxanthine nucleotide (IMP) is synthesized, and then IMP is converted into adenine nucleotide (AMP) and guanine nucleotide (GMP). The sources of purine ring elements are as follows: N 1 provided by aspartic acid, C2 provided by N 10- formyl FH4, C8 provided by N5, N 10- methylacetylene FH4, N3 and N9 provided by glutamine, C4, C5 and N7 provided by glycine, and C6 provided by CO2. The characteristic of de novo synthesis of purine nucleotides is that purine nucleotides are synthesized step by step on the basis of phosphoribosyl molecules, instead of synthesizing purine bases alone and then combining with phosphoribosyl. The key enzymes in the reaction process include PRPP amidase and PRPP synthetase. PRPP amidase is an allosteric enzyme, and its monomer form is active, while its dimer form is inactive. IMP, AMP and GMP convert active forms into inactive forms, while PRPP is the opposite. The regulation mechanism of de novo synthesis is feedback regulation, which mainly occurs in the following parts: the activities of PRPP synthetase and PRPP amidase in the initial stage of purine nucleotide synthesis can be inhibited by synthetic products IMP, AMP and GMP; During the formation of AMP and GMP, excessive AMP controls the formation of AMP without affecting the synthesis of GMP, while excessive GMP controls the formation of GMP without affecting the synthesis of AMP. GTP is needed when IMP is converted into AMP, and ATP is needed when IMP is converted into GMP.
2. Remedial synthesis of purine nucleotides
The main enzymes in the reaction include adenine phosphoribosyltransferase (APRT) and hypoxanthine guanine phosphoribosyltransferase (HGPRT). Physiological significance of remedial synthesis of purine nucleotides: saving energy and some amino acids in de novo synthesis: some tissues and organs in the body, such as brain and bone marrow, can only carry out remedial synthesis of purine nucleotides because of the lack of enzyme system for de novo synthesis of purine nucleotides.
3. Mutual transformation of purine nucleotides
IMP can be converted into AMP and GMP, and AMP and GMP can also be converted into IMP. AMP and GMP can be transformed into each other.
4. Production of deoxynucleotides
Deoxynucleotides in vivo are reduced by their corresponding ribonucleotides at diphosphate level. Ribonucleotide reductase catalyzes this reaction. 5. Antimetabolites of purine nucleotides ① Purine analogues: 6- mercaptopurine (6MP), 6- mercaptoguanine, 8- azaguanine, etc. 6MP is widely used and its structure is similar to hypoxanthine. It can be phosphorylated in vivo to produce 6MP nucleotides. In this way, it can inhibit the reaction from IMP to AMP and GMP. ② Amino acid analogues: diazoserine and 6- diazo -5- oxynorleucine. The structure is similar to glutamine, which can interfere with the role of glutamine in purine nucleotide synthesis, thus inhibiting purine nucleotide synthesis. ③ Folate analogues: Methotrexate and methotrexate (MTX) are analogues of folic acid, which can competitively inhibit dihydrofolate reductase, so that folic acid cannot be reduced to dihydrofolate and tetrahydrofolate, thus inhibiting the synthesis of purine nucleotides.
Edit the catabolism of purine in this paragraph.
The basic process of purine nucleotide catabolism reaction is that nucleotides are hydrolyzed into nucleosides by nucleotidase, and then hydrolyzed into free bases and 1- ribose phosphate by enzyme. Purine base is finally decomposed into uric acid, which is excreted with urine. Xanthine oxidase is an important enzyme in catabolism. Purine nucleotide catabolism mainly occurs in liver, small intestine and kidney. Abnormal purine metabolism: Gout is caused by excessive uric acid, and the uric acid content in patients' blood increases and purine decomposes.
High uric acid crystals can be deposited in joints, soft tissues, cartilage and kidneys, leading to arthritis, urinary calculi and kidney diseases. Allopurinol is commonly used to treat gout in clinic. Basic concept 1. Ab initio synthesis: In the synthesis and metabolism of purine nucleotides in vivo, purine nucleotides are synthesized from phosphoribosyl, amino acids, a carbon unit and CO2 through a series of enzymatic reactions, which is called ab initio synthesis. 2. Remedial pathway: Purine nucleotide is synthesized by using free purine or purine nucleoside in vivo through a simple reaction process, which is called remedial pathway. 3. Self-destructive appearance: Lesch-Nyhan syndrome, also known as Lesch-Nyhan syndrome, is a child who has completely lost HGPRT due to the deletion of some genes, showing self-destructive appearance. [ 1].