Pathways

5-Oxoprolinuria (5-Oxoprolinase deficiency) is a result of a defect in the gamma-glutamyl cycle due to either 5-oxoprolinase or glutathione synthetase deficiency. In the case of glutathione synthetase deficiency, the glycine is not incorporated into gamma-glutamylcysteine. In the case of 5-oxoprolinase, however, pyroglutamic acid accumulates. Symptoms include anemia, mental retardation, metabolic acidosis, respiratory distress and urolithiasis.

Abacavir (also known as Ziagen or Epzicom) is an antiviral agent that is used for treating HIV/AID. Cellular enzyme converts abacavir to its activate metabolite, carbovir triphosphate, for inhibiting HIV-1 reverse transcriptase (RT) by competing with dGTP, which is the natural substrate of RT. Without HIV-1 reverse transcriptase, complementary DNA (cDNA) could not be generated; therefore, viral DNA couldn't be completed.

Abacavir is an oral antiviral drug used to treat HIV/AIDS. It is a nucleotide analog reverse transcriptase inhibitor that targets HIV infected cells in the body. When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell. Abacavir enters the cell via solute carrier family 22 member 1 and is converted into abacavir 5’-monophosphate by adenosine kinase. Adenosine deaminase-like protein then converts abacavir 5’-monophosphate into carbovir monophosphate. The carbovir monophosphate is metabolized to carbovir diphosphate via guanylate kinase. Finally, the catalyzation of carbovir diphosphate to carbovir triphosphate occurs. Carbovir triphosphate is an analog of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dGTP and by incorporation into viral DNA. Carbovir triphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once carbovir triphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed. Common side effects from taking abacavir include diarrhea, nausea, fatigue, headache, loss of appetite and hypersentitvity reactions (fever, skin rash, gastrointestinal and respiratory symptoms)

Abacavir is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Abacavir passes through the liver and is then excreted from the body mainly through the kidney.