GART

Glycinamide ribonucleotide transformylase (GART) is an enzyme that plays a crucial role in the purine biosynthesis pathway, which is essential for DNA and RNA synthesis. This enzyme catalyzes the addition of a formyl group to glycinamide ribonucleotide (GAR), producing formylglycinamide ribonucleotide (FGAR), a critical step in the formation of purine nucleotides.

Function

GART is involved in the de novo synthesis of purine nucleotides, which are the building blocks of DNA and RNA. This pathway is vital for cell growth and division, making GART an important enzyme in all living cells, especially rapidly dividing cells such as those found in the bone marrow and gastrointestinal tract. The activity of GART is tightly regulated, as imbalances in purine synthesis can lead to various diseases, including cancer and autoimmune diseases.

Structure

GART is a multi-domain protein that is part of a larger complex known as trifunctional purine biosynthetic protein adenosine-3. The enzyme consists of several domains, each responsible for different enzymatic activities involved in the purine biosynthesis pathway. The structure of GART allows it to efficiently catalyze the transformation of GAR to FGAR, a key step in the pathway.

Clinical Significance

Alterations in the activity or expression of GART can lead to a variety of medical conditions. Overexpression of GART has been observed in certain types of cancer, suggesting a role in tumorigenesis. Conversely, genetic defects in GART can result in purine biosynthesis disorders, which are rare metabolic conditions characterized by various symptoms, including developmental delays and neurological issues.

Inhibitors of GART are being studied as potential therapeutic agents for cancer and autoimmune diseases. By targeting the purine biosynthesis pathway, these inhibitors can reduce the proliferation of rapidly dividing cells, offering a strategy for treating diseases associated with excessive cell growth.

Genetics

The GART gene is located on human chromosome 21. Mutations in this gene can lead to disorders of purine metabolism. Genetic studies have also explored the relationship between variations in the GART gene and susceptibility to certain diseases, including its potential role in the pathogenesis of Down syndrome, given the gene's location on chromosome 21.

See Also

• Purine metabolism
• DNA synthesis
• RNA synthesis
• Cancer
• Autoimmune diseases