Definition

A class of compounds consisting of a purine base or a pyrimidine base, ribose or deoxyribose, and phosphoric acid. Also known as nuclear niacin. The five-carbon sugar synthesizes a nucleoside with an organic base, the nucleoside and the phosphate synthesize a nucleotide, and the four nucleotides constitute a nucleic acid. Nucleotides are mainly involved in the formation of nucleic acids, and many single nucleotides also have a variety of important biological functions, such as adenosine triphosphate (ATP), dehydrogenase, and the like related to energy metabolism. Certain nucleotide analogs can interfere with nucleotide metabolism and can be used as anticancer drugs. Depending on the sugar, nucleotides include ribonucleotides and deoxynucleotides. According to the base, there are adenine nucleotides (adenosine, AMP), guanine nucleotides (guanine, GMP), cytosine nucleotides (cytidine, CMP), uridine nucleus Glucuronide (uridine, UMP), thymidine (thymidylate, TMP) and hypoxanthine (inosinic acid, IMP). The phosphoric acid in the nucleotide is in the form of one molecule, two molecules, and three molecules. In addition, the inside of the nucleotide molecule can also be dehydrated and condensed into a cyclic nucleotide synthesis



Nucleotides are the basic building blocks of ribonucleic acid and deoxyribonucleic acid, and are precursors for the synthesis of nucleic acids in vivo. Nucleotides are distributed in the nucleus and cytoplasm of various organs, tissues, and cells in the living body, and participate in the basic life activities of the inheritance, development, and growth of the organism as components of the nucleic acid. There are also a significant number of nucleotides present in free form in the organism. Adenosine triphosphate plays a major role in cellular energy metabolism. The release and absorption of energy in the body is mainly manifested by the production and consumption of adenosine triphosphate. In addition, uridine triphosphate, cytidine triphosphate and guanosine triphosphate are also sources of energy in the anabolism of some substances. Adenylate is also a component of certain coenzymes such as coenzyme I, II and coenzyme A.



In vivo, nucleotides can be synthesized from simple compounds. These synthetic raw materials include aspartic acid, glycine, glutamine, one carbon unit, and CO2. The purine nucleotides are catabolized in the body to produce uric acid, and pyrimidine nucleotides are decomposed to form CO2, β-alanine and β-aminoisobutyric acid. Metabolic disorders of purine nucleotides and pyrimidine nucleotides can cause clinical symptoms (see purine metabolic disorders, pyrimidine metabolic disorders).

Nucleotide compounds are also used as drugs for clinical treatment, such as 5-fluorouracil and 6-mercaptopurine, which are commonly used in tumor chemotherapy.



Some nucleotide molecules have only one phosphate group, so they can be called nucleoside monophosphate (NMP). The 5'-nucleotide phosphate group can be further phosphorylated to form nucleoside diphosphate (NDP) and nucleoside triphosphate (NTP), wherein the phosphoric acid is linked by high energy bonds. The same is true for deoxynucleotides.



There is also a class of cyclized nucleotides in the body, that is, the phosphoric acid moiety in the single nucleotide is simultaneously dehydrated and condensed with the third and fifth carbon atoms in the ribose to form a cyclic diester, ie, a 3', 5'-cyclized core. Glycosylates, important are 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP).



Distributed


Nucleotides are the basic structural units of nucleic acids, and the nucleotides in the human body are mainly synthesized by the organisms themselves. Nucleotides are widely distributed in the body. The cells are mainly present in the form of 5'-nucleotides. The concentration of ribonucleotides in the cells far exceeds that of deoxyribonucleotides. The contents of various nucleotides in different types of cells vary greatly. In the same cell, the contents of various nucleotides are also different, and the total amount of nucleotides does not change much.


Features



Nucleotide compounds have important biological functions and they are involved in almost all biochemical reactions in living organisms. It is summarized in the following five aspects:

1 Nucleotide is the precursor of synthetic biomacromolecules (RNA) and deoxyribonucleic acid (DNA). There are four main types of nucleotides in RNA: AMP, GMP, CMP and UMP. Nucleotide de novo synthesis of precursors are simple substances such as phosphoribosose, amino acids, one carbon unit, and carbon dioxide. There are four main types of deoxynucleotides in DNA: dAMP, dGMP, dCMP, and dTMP, which are reduced by their respective nucleocarbon nucleotides at the diphosphate level.



2 ATP (ATP) plays an extremely important role in cellular energy metabolism. Part of the energy produced by the substance during oxidation is stored in

The high energy phosphate bond of the ATP molecule. The ATP molecule's liberating energy response can be combined with various biological reactions that require energy to perform various physiological functions, such as anabolism of the substance, muscle contraction, absorption and secretion, body temperature maintenance, and bioelectric activity. Therefore, ATP can be considered as the center of energy metabolism transformation.



3 ATP can also transfer high-energy phosphate bonds to UDP, CDP, and GDP to generate UTP, CTP, and GTP. They are also a direct source of energy in some anabolic processes. Moreover, in some synthetic reactions, some nucleotide derivatives are also activated intermediate metabolites. For example, UTP is involved in glycogen synthesis to supply energy, and UDP also carries the role of transporting glucose.



4 Adenylate is also an important coenzyme, such as coenzyme I (nicotinamide adenine dinucleotide, (NAD+), coenzyme II (nicotinamide adenine dinucleotide, NADP+), flavin adenine dinucleoside The components of acid (FAD) and coenzyme A (CoA). NAD+ and FAD are important components of biooxidation system and play an important role in the transfer of hydrogen atoms or electrons. CoA, as a coenzyme component of some enzymes, participates in the aerobic oxidation of sugars. And fatty acid oxidation.



5 nucleotides have a certain regulatory effect on many basic biological processes. The basic components of all living things play a dominant role in the growth, development, reproduction and inheritance of living things. For example, in milk powder as a function to maintain the normal function of the baby's gastrointestinal tract, reduce diarrhea and constipation, improve immunity, and reduce the risk of illness.

Metabolism



It can be discussed from three aspects: anabolism, catabolism and metabolic regulation.



Anabolic



Purine nucleotide

It is mainly synthesized from simple compounds such as aspartic acid, glycine, glutamine, CO2 and one carbon unit (formyl and methine, carried by tetrahydrofolate). They synthesize hypoxanthine nucleotides (also known as inosinic acid) by an enzymatic reaction in 11 steps. Subsequently, inosinic acid is aminated at different sites to convert to adenosine and guanylate. The first step in the synthetic pathway is the activation of 5-phosphate ribose by enzymatic catalysis to produce 5-phosphate ribose 1-pyrophosphate (PRPP), this is an important response. De novo synthesis of purine nucleotides is mainly carried out in the liver, followed by in the small intestine mucosa and thymus.



Deuterium nucleotide degradation can produce purine base, which is finally decomposed into uric acid, and some of the decomposition products can be reused to synthesize purine nucleotides. This is called recovery anabolic pathway and can be carried out in tissues such as bone marrow and spleen. Adenine, guanine and hypoxanthine produced by purine nucleotide degradation are catalyzed by phosphoribosyltransferase and receive phosphoribose in 3'-pyrophosphate-5-phosphate ribose (PRPP) molecule to form corresponding nucleus Glycosylate. This synthetic route also has a certain meaning.



De novo synthesis of pyrimidine nucleotides is also primarily carried out in the liver. The synthetic raw materials are carbamoylphosphoric acid and aspartic acid. The carbamoylphosphoric acid and aspartic acid form a uridine acid after several steps of enzymatic reaction, and after the uridine is converted into uridine triphosphate, the amino group is received from glutamine to form cytidine triphosphate.

The above-described in vivo synthesized purine and pyrimidine nucleotides are all nucleoside monophosphates. They can all accept the phosphate group provided by ATP under the catalysis of phosphokinase and further convert into nucleoside diphosphate and nucleoside triphosphate.



There is also a class of deoxyribonucleotides in the body. They are dAMP, dGMP, dCMP and dTMP. The deoxyribose in their composition is not formed into a nucleotide molecule but is produced by the reduction of the synthesized ribonucleotides. This reduction occurs at the molecular level of the nucleoside diphosphate, and dADP, dGDP, dCDP, and dUDP can all be derived from this, but dTMP is different, which is produced by methylation of dUMP.



Catabolism

The purine nucleotides are catabolized in the body, and deuterated to produce hypoxanthine and xanthine, and then oxidized by the xanthine oxidase to form uric acid. Uric acid can be excreted with the urine, and the daily uric acid output of normal people is 0.6g. The decomposition products of pyrimidine nucleotides in the body are CO2, β-alanine and β-aminoisobutyric acid.



Metabolic regulation

The synthesis of nucleotides in the body is regulated by feedback. The end products of purine nucleotide synthesis are AMP and GMP, which can feedbackly inhibit the conversion from IMP to AMP and GMP. They can feedbackly inhibit the production of the initial reaction PRPP of the synthetic pathway in concert with IMP. The product of pyrimidine nucleotide synthesis, CTP, also feedbackly inhibits the initial reaction of pyrimidine synthesis.



About us

We leverage our wide spectrum of business in the fields of development, manufacturing, marketing, and distribution to help you make best-informed decisions tailored to your evolving needs for premium chemicals. Our complete suite of CRO services spans the entire molecule development pipeline including Apoptosis Signaling Pathway,B Cell Receptor Signaling Pathway,CTLA4 Signaling Pathway,EGFR Signaling Pathway.