Deoxyguanosine triphosphate

Deoxyguanosine triphosphate (dGTP) is a nucleotide derivative that is used as a substrate in DNA synthesis. It is one of the four building blocks of DNA, alongside deoxyadenosine triphosphate (dATP), deoxycytidine triphosphate (dCTP), and deoxythymidine triphosphate (dTTP). dGTP plays a crucial role in cellular processes, including DNA replication and DNA repair mechanisms.

Structure and Function

dGTP consists of the nucleoside deoxyguanosine linked to three phosphate groups. The molecule serves as a monomer in the synthesis of DNA. During DNA replication, dGTP is incorporated into the growing DNA strand by the enzyme DNA polymerase. The incorporation of dGTP, as with the other deoxynucleotide triphosphates, is guided by the complementary base pairing rules, with dGTP pairing with cytosine (C) in the template strand.

Biosynthesis

The biosynthesis of dGTP occurs through the salvage pathway and the de novo synthesis pathway. In the salvage pathway, dGTP is synthesized from guanine or deoxyguanosine through the action of specific enzymes, including guanine phosphoribosyltransferase (GPRT). In de novo synthesis, dGTP is synthesized from ribonucleotide reductase-mediated reduction of guanosine triphosphate (GTP).

Regulation

The cellular concentration of dGTP (and other deoxynucleotide triphosphates) is tightly regulated to ensure faithful DNA replication and repair. Imbalances in dGTP levels can lead to mutations and genomic instability. Enzymes such as ribonucleotide reductase play a key role in maintaining the balance of deoxynucleotide triphosphates.

Clinical Significance

Alterations in dGTP metabolism have been implicated in various diseases, including cancer and immunodeficiency disorders. For example, mutations in enzymes involved in dGTP metabolism can lead to an imbalance in deoxynucleotide levels, contributing to the development of cancer. Additionally, certain antiviral and anticancer drugs target dGTP metabolism to inhibit DNA synthesis in viruses or cancer cells.

See Also

• Nucleic acid metabolism
• Purine metabolism
• DNA polymerase
• Ribonucleotide reductase