What does purine nucleotide cycle mean

The purine nucleotide cycle refers to a method of amino acid deamination in human skeletal muscle, that is, the deoxygenation of the transamination-coupled cup AMV cycle. In the role of amino group, it can generate aspartic acid and sulfapurine nucleotide. This can maintain the balance of adenine and guanine nucleotide levels in the human body, thus ensuring the needs of nucleic acid synthesis, which is of great significance to the human body.

Synthetic pathway

There are two pathways for the synthesis of nucleotides in the body: ① The process of synthesizing nucleotides using simple substances such as ribose phosphate, amino acids, one-carbon units and CO2 as raw materials is called de novo synthesis, which is the main synthesis pathway in the body. ② The process of using free bases or nucleosides in the body to generate nucleotides through a simple reaction process is called the salvage pathway. In some tissues such as the brain and bone marrow, nucleotides can only be synthesized through this pathway. The main salvage synthesis pathway of purine nucleotides is the formation of purine nucleotides by the action of purine base and 5'-PRPP (5'-phosphoribosyl pyrophosphate) under the action of phosphoribosyl transferase.

Synthesis process

De novo synthesis of purine nucleotides

As early as 1948, Buchanan et al. used isotope tracing technology to feed pigeons with different isotope-labeled compounds and measured the position of labeled atoms in the excreted uric acid. They confirmed that the precursors of purine synthesis were: amino acids (glycine, aspartic acid, and glutamine), CO2, and one-carbon units (N10-formyl FH4, N, N10-formyl FH4).

Subsequently, Buchanan, Greenberg and others further clarified the synthesis process of purine nucleotides. Surprisingly, the synthesis of purine nucleotides in the body does not start with the synthesis of the purine base and then combines with ribose and phosphate, but rather the stepwise synthesis of purine nucleotides based on ribose phosphate. The de novo synthesis of purine nucleotides mainly occurs in the cytosol and can be divided into two stages: first, inosine monophosphate (IMP) is synthesized; then AMP and GMP are generated through different pathways. The following is a step-by-step introduction to the synthesis process of purine nucleotides.

Regulation of de novo synthesis

Regulation of de novo purine nucleotide synthesis

De novo synthesis is the major pathway for the synthesis of purine nucleotides in vivo. But this process consumes amino acids and ATP. The body has a fine regulation of the synthesis rate. In most cells, the synthesis of IMP, ATP, and GTP is regulated separately, not only to regulate the total amount of purine nucleotides but also to keep the levels of ATP and GTP in relative balance.

The regulation of the IMP pathway is mainly in the first two steps of synthesis, namely catalyzing the production of PRPP and PRA. Ribose phosphate pyrophosphokinase is feedback inhibited by ADP and GDP. Phosphoribosylamidotransferase is feedback inhibited by ATP, ADP, AMP and GTP, GDP, and GMP. ATP, ADP, and AMP bind to one inhibitory site of the enzyme, while GTP, GDP, and GMP bind to the other inhibitory site. Thus, the rate of IMP production is regulated independently and coordinately by adenine and guanine nucleotides. In addition, PRPP can allosterically activate phosphoribosylamidotransferase.

The second level of regulation affects the conversion of IMP to AMP and GMP. GMP feedback inhibits the conversion of IMP to XMP, while AMP feedback inhibits the conversion of IMP to adenylate succinate, thereby preventing the formation of excessive AMP and GMP. Furthermore, the synthesis of adenine and guanine is in balance. GTP accelerates the conversion of IMP to AMP, while ATP promotes the production of GMP, thus keeping the levels of adenine and guanine nucleotides relatively balanced to meet the needs of nucleic acid synthesis.