nucleoside triphosphate biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of a nucleoside triphosphate, a compound consisting of a nucleobase linked to a deoxyribose or ribose sugar esterified with triphosphate on the sugar. [GOC:go_curators, ISBN:0198506732]

Nucleoside triphosphate biosynthesis is a fundamental process in all living organisms, responsible for generating the building blocks of DNA and RNA. These building blocks, known as nucleoside triphosphates (NTPs), are composed of a nitrogenous base (adenine, guanine, cytosine, thymine, or uracil), a five-carbon sugar (ribose or deoxyribose), and three phosphate groups. The process involves multiple enzymatic steps and can be broadly divided into two main pathways: de novo synthesis and salvage pathways.

**De novo synthesis:**

* **Purine biosynthesis:** Initiates with the formation of PRPP (phosphoribosyl pyrophosphate) from ribose-5-phosphate, followed by a series of complex reactions involving amino acids (glycine, glutamine, aspartate), tetrahydrofolate, and various enzymes like amidophosphoribosyltransferase, glycinamide ribotide synthetase, GAR transformylase, and others. The pathway culminates in the synthesis of IMP (inosine monophosphate), a precursor for both AMP (adenosine monophosphate) and GMP (guanosine monophosphate).
* **Pyrimidine biosynthesis:** Begins with the condensation of carbamoyl phosphate and aspartate to form carbamoyl aspartate. Subsequent steps involve reactions catalyzed by dihydroorotase, dihydroorotate dehydrogenase, and orotate phosphoribosyltransferase, leading to the formation of UMP (uridine monophosphate). UMP is then converted to CTP (cytidine triphosphate) via a series of enzymatic reactions.

**Salvage pathways:**

* These pathways utilize pre-existing purine and pyrimidine bases or nucleosides obtained from the breakdown of nucleic acids or dietary sources.
* The major enzymes involved in salvage pathways are adenine phosphoribosyltransferase (APRT) for adenine, hypoxanthine-guanine phosphoribosyltransferase (HGPRT) for hypoxanthine and guanine, and thymidine kinase for thymidine.

**Phosphorylation of nucleoside monophosphates:**

* Once nucleoside monophosphates (AMP, GMP, CMP, UMP) are formed, they are sequentially phosphorylated to diphosphates and then triphosphates by specific kinases. These reactions require ATP as the phosphate donor.

**Regulation:**

* Nucleoside triphosphate biosynthesis is tightly regulated to maintain balanced levels of NTPs. This regulation involves feedback inhibition, substrate availability, and allosteric regulation of key enzymes.

**Clinical significance:**

* Defects in nucleoside triphosphate biosynthesis can lead to various genetic disorders, including Lesch-Nyhan syndrome (deficiency in HGPRT), SCID (severe combined immunodeficiency) due to defects in purine biosynthesis, and orotic aciduria (deficiency in uridine monophosphate synthase).
* Some anticancer drugs target specific enzymes involved in NTP synthesis, inhibiting cell proliferation.

This complex and vital process ensures the constant supply of building blocks for DNA and RNA, crucial for genetic information storage, gene expression, and overall cell function.'
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Proteins (2)

Compounds (21)