AGXT: Difference between revisions

Latest revision as of 22:31, 15 December 2024

AGXT

The AGXT gene encodes the enzyme alanine-glyoxylate aminotransferase, which is primarily expressed in the liver. This enzyme plays a crucial role in the detoxification of glyoxylate, a byproduct of metabolism, by converting it into glycine. Mutations in the AGXT gene can lead to a rare genetic disorder known as primary hyperoxaluria type 1 (PH1), characterized by the overproduction of oxalate, leading to kidney stones and renal failure.

Structure and Function[edit]

The AGXT gene is located on chromosome 2q37.3 and consists of 11 exons. The enzyme alanine-glyoxylate aminotransferase is a pyridoxal phosphate-dependent enzyme that catalyzes the transamination reaction between glyoxylate and L-alanine to produce glycine and pyruvate. This reaction is essential for the detoxification of glyoxylate, preventing its conversion to oxalate.

Clinical Significance[edit]

Mutations in the AGXT gene are responsible for primary hyperoxaluria type 1 (PH1), an autosomal recessive disorder. PH1 is characterized by the excessive production of oxalate, which combines with calcium to form calcium oxalate stones in the kidneys and urinary tract. Over time, this can lead to kidney damage and end-stage renal disease.

Diagnosis[edit]

Diagnosis of PH1 typically involves genetic testing to identify mutations in the AGXT gene. Biochemical tests may also be conducted to measure oxalate levels in the urine and plasma.

Treatment[edit]

Management of PH1 includes high fluid intake, dietary modifications, and medications to reduce oxalate production. In severe cases, liver transplantation may be necessary, as the liver is the primary site of AGXT expression and activity.

Genetic Variants[edit]

Several mutations in the AGXT gene have been identified, including missense, nonsense, and splice-site mutations. The most common mutation in Caucasian populations is the c.508G>A (p.Gly170Arg) mutation, which affects the enzyme's stability and function.

Research and Future Directions[edit]

Research is ongoing to develop gene therapy and other novel treatments for PH1. Understanding the molecular mechanisms of AGXT mutations and their effects on enzyme function is crucial for developing targeted therapies.

Also see[edit]

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-<br>= 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).
+The AGXT gene encodes the enzyme alanine-glyoxylate aminotransferase, which is primarily expressed in the liver. This enzyme plays a crucial role in the detoxification of glyoxylate, a byproduct of metabolism, by converting it into glycine. Mutations in the AGXT gene can lead to a rare genetic disorder known as primary hyperoxaluria type 1 (PH1), characterized by the overproduction of oxalate, leading to kidney stones and renal failure.
-== Function ==
+==Structure and 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.
+The AGXT gene is located on chromosome 2q37.3 and consists of 11 exons. The enzyme alanine-glyoxylate aminotransferase is a pyridoxal phosphate-dependent enzyme that catalyzes the transamination reaction between glyoxylate and L-alanine to produce glycine and pyruvate. This reaction is essential for the detoxification of glyoxylate, preventing its conversion to oxalate.
-== Genetic and Molecular Biology ==
+==Clinical Significance==
-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 are responsible for primary hyperoxaluria type 1 (PH1), an autosomal recessive disorder. PH1 is characterized by the excessive production of oxalate, which combines with calcium to form calcium oxalate stones in the kidneys and urinary tract. Over time, this can lead to kidney damage and end-stage renal disease.
-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.
+===Diagnosis===
+Diagnosis of PH1 typically involves genetic testing to identify mutations in the AGXT gene. Biochemical tests may also be conducted to measure oxalate levels in the urine and plasma.
-== Clinical Significance ==
+===Treatment===
-=== Primary Hyperoxaluria Type 1 (PH1) ===
+Management of PH1 includes high fluid intake, dietary modifications, and medications to reduce oxalate production. In severe cases, liver transplantation may be necessary, as the liver is the primary site of AGXT expression and activity.
-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.
+==Genetic Variants==
+Several mutations in the AGXT gene have been identified, including missense, nonsense, and splice-site mutations. The most common mutation in Caucasian populations is the c.508G>A (p.Gly170Arg) mutation, which affects the enzyme's stability and function.
-=== Treatment ===
+==Research and Future Directions==
-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 is ongoing to develop gene therapy and other novel treatments for PH1. Understanding the molecular mechanisms of AGXT mutations and their effects on enzyme function is crucial for developing targeted therapies.
-== Research and Future Directions ==
+==Also see==
-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.
+* [[Primary hyperoxaluria]]
+* [[Kidney stones]]
+* [[Liver transplantation]]
+* [[Genetic testing]]
-== References ==
+{{Genetics}}
-* Cochat, P., & Rumsby, G. (2013). Primary hyperoxaluria. ''New England Journal of Medicine'', 369(7), 649-658.
+{{Enzymes}}
-* 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)
+[[Category:Genetics]]
 [[Category:Enzymes]]
 [[Category:Metabolic disorders]]
-[[Category:Genetic diseases and disorders]]
+[[Category:Kidney diseases]]