purine nucleotide biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of a purine nucleotide, a compound consisting of nucleoside (a purine base linked to a deoxyribose or ribose sugar) esterified with a phosphate group at either the 3' or 5'-hydroxyl group of the sugar. [GOC:go_curators, ISBN:0198506732]

Purine nucleotide biosynthesis is a complex metabolic pathway responsible for generating the purine nucleotides adenosine monophosphate (AMP) and guanosine monophosphate (GMP). These nucleotides are essential building blocks for nucleic acids (DNA and RNA), as well as for numerous other cellular processes, including energy production, signal transduction, and regulation of gene expression.

The biosynthesis pathway can be divided into two main phases:

**1. De novo synthesis:**

- **Step 1: Formation of PRPP (Phosphoribosyl pyrophosphate):** Ribose-5-phosphate, derived from the pentose phosphate pathway, is phosphorylated by ribose-5-phosphate pyrophosphokinase to generate PRPP. This is the first committed step in purine nucleotide biosynthesis.

- **Step 2: Attachment of glycine:** PRPP reacts with glutamine to produce formylglycinamide ribonucleotide (FGAR) via the enzyme amidophosphoribosyl transferase (PPAT).

- **Step 3: Incorporation of glycine and subsequent modifications:** FGAR undergoes a series of reactions, including the addition of glycine and formyl groups, leading to the formation of formyltetrahydrofolate (THF) and 5'-phosphoribosylglycinamide (GAR).

- **Step 4: Formation of inosinic acid (IMP):** GAR is further transformed into 5'-phosphoribosylaminoimidazole (AIR), then to 5'-phosphoribosylaminoimidazole carboxamide (AICAR), and finally to inosinic acid (IMP). This step involves the addition of aspartate and the removal of CO2.

**2. Conversion of IMP to AMP and GMP:**

- **Formation of AMP:** IMP is converted to adenylosuccinate by the enzyme adenylosuccinate synthetase. Adenylosuccinate is then hydrolyzed to AMP by adenylosuccinate lyase.

- **Formation of GMP:** IMP is oxidized to xanthosine monophosphate (XMP) by IMP dehydrogenase. XMP is then converted to GMP by the enzyme GMP synthetase.

**Regulation:**

Purine nucleotide biosynthesis is tightly regulated by feedback mechanisms. High levels of AMP and GMP inhibit key enzymes involved in the pathway, such as PRPP synthetase and glutamine-PRPP amidotransferase.

**Clinical Significance:**

Defects in purine nucleotide biosynthesis can lead to a variety of genetic disorders, such as Lesch-Nyhan syndrome and SCID. These disorders can cause neurological, developmental, and immune system problems.

**Pharmaceutical Importance:**

Inhibitors of purine nucleotide biosynthesis are used as chemotherapeutic agents to treat cancer. For example, 6-mercaptopurine is a common drug used to treat leukemia.

**In summary, purine nucleotide biosynthesis is a crucial metabolic pathway that provides the building blocks for nucleic acids and many other essential cellular processes. The pathway is tightly regulated to ensure adequate levels of purine nucleotides for cellular needs. Disruptions in the pathway can have serious consequences for human health.**'
"

Proteins (7)

Compounds (18)