AGXT

= AGXT =

AGXT (Alanine-glyoxylate aminotransferase) is an enzyme that plays a crucial role in the metabolism of glyoxylate and alanine. It is primarily found in the liver and is encoded by the AGXT gene in humans. This enzyme is of significant clinical interest due to its association with the metabolic disorder known as Primary Hyperoxaluria Type 1 (PH1).

Function

AGXT catalyzes the transamination reaction between alanine and glyoxylate to produce pyruvate and glycine. This reaction is important for the detoxification of glyoxylate, preventing its conversion to oxalate, which can lead to the formation of kidney stones and renal failure if accumulated in high concentrations.

Genetic and Molecular Biology

The AGXT gene is located on chromosome 2q37.3. It consists of 11 exons and encodes a protein of 392 amino acids. The enzyme is a homodimer, meaning it functions as a pair of identical subunits.

Mutations in the AGXT gene can lead to a deficiency or dysfunction of the AGXT enzyme, resulting in the accumulation of glyoxylate and its subsequent conversion to oxalate. This is the underlying cause of Primary Hyperoxaluria Type 1.

Clinical Significance

Primary Hyperoxaluria Type 1 (PH1)

PH1 is an autosomal recessive disorder characterized by the overproduction of oxalate, leading to recurrent kidney stones, nephrocalcinosis, and eventually renal failure. Patients with PH1 often present in childhood with symptoms related to kidney stones or renal impairment.

Diagnosis of PH1 is confirmed by genetic testing for mutations in the AGXT gene. Over 150 mutations have been identified, with the most common being the Gly170Arg and Phe152Ile mutations.

Treatment

Management of PH1 includes high fluid intake, dietary modifications, and the use of medications such as pyridoxine (vitamin B6), which can enhance residual AGXT activity in some patients. In severe cases, liver transplantation may be necessary, as the liver is the primary site of AGXT activity.

Research and Future Directions

Research into gene therapy and enzyme replacement therapy for PH1 is ongoing. These approaches aim to correct the underlying genetic defect or provide functional AGXT enzyme to patients, potentially offering a cure for this debilitating condition.

References

• Cochat, P., & Rumsby, G. (2013). Primary hyperoxaluria. New England Journal of Medicine, 369(7), 649-658.
• Danpure, C. J. (2005). Primary hyperoxaluria: from gene defects to designer drugs? Nephrology Dialysis Transplantation, 20(8), 1525-1529.
• Williams, E. L., Acquaviva, C., Amoroso, A., Chevalier, F., Coulter-Mackie, M., Monico, C. G., ... & Rumsby, G. (2009). Primary hyperoxaluria type 1: update and additional mutation analysis of the AGXT gene. Human Mutation, 30(6), 910-917.

External Links

• [OMIM Entry on AGXT](https://www.omim.org/entry/259900)
• [GeneCards: AGXT](https://www.genecards.org/cgi-bin/carddisp.pl?gene=AGXT)