AGXT - Alanine Glyoxylate Aminotransferase | Elisa - Clia - Antibody - Protein

Background:

Alanine glyoxylate aminotransferase (AGXT) is a key enzyme involved in the metabolism of glyoxylate, a compound derived from various metabolic processes. AGXT is primarily expressed in the liver and kidneys, where it plays a critical role in the detoxification of glyoxylate by converting it to glycine. This enzymatic reaction is essential for preventing the accumulation of oxalate, which can lead to the formation of kidney stones and other complications. Mutations in the AGXT gene can result in a rare genetic disorder known as primary hyperoxaluria type 1 (PH1), characterized by excessive oxalate production and deposition in the kidneys and other tissues. PH1 can lead to kidney failure and systemic complications if left untreated. Management of PH1 often involves dietary modifications, medications to reduce oxalate production, and, in severe cases, liver or kidney transplantation. Understanding the role of AGXT in oxalate metabolism is crucial for the diagnosis and management of PH1 and related disorders. Ongoing research aims to develop novel therapeutic approaches targeting AGXT to alleviate the burden of oxalate-related diseases.

Protein Structure:

• Molecular Weight: Approximately 43 kDa.
• Primary Structure: AGXT consists of 392 amino acids.
• Domain: The enzyme belongs to the class of pyridoxal phosphate (PLP)-dependent aminotransferases, which require PLP as a cofactor.
• Subcellular Localization: AGXT is primarily located in the peroxisomes of liver cells, though it has isoforms that can also localize to the mitochondria.
• Secondary and Tertiary Structures: AGXT's structure includes alpha-helices and beta-sheets, typical of aminotransferases, which form a compact and stable conformation necessary for its enzymatic activity.

Classification and Subtypes:

• Enzyme Classification: AGXT is classified under EC 2.6.1.44.
• Isoforms: There are two main isoforms due to alternative splicing: AGXT1 and AGXT2, with AGXT1 being the predominant and more extensively studied form.

Function and Biological Significance:

• Metabolic Role: AGXT catalyzes the transamination reaction, converting glyoxylate and alanine to glycine and pyruvate. This process is crucial in detoxifying glyoxylate.
• Prevention of Oxalate Formation: By converting glyoxylate to glycine, AGXT prevents the conversion of glyoxylate to oxalate, thereby reducing the risk of calcium oxalate kidney stone formation.
• Detoxification: The enzyme helps in detoxifying glyoxylate, which can be harmful in high concentrations.

Interactions:

• Cofactors: AGXT requires pyridoxal phosphate (PLP) as a cofactor for its aminotransferase activity.
• Substrates: The primary substrates for AGXT are glyoxylate and L-alanine.
• Metabolic Pathways: AGXT is involved in the glyoxylate and dicarboxylate metabolism pathways.

Clinical Issues:

• Primary Hyperoxaluria Type 1 (PH1): Mutations in the AGXT gene can lead to PH1, a rare genetic disorder characterized by the overproduction of oxalate, leading to recurrent kidney stones and renal failure. PH1 patients have deficient or mistargeted AGXT enzyme, resulting in the accumulation of glyoxylate and its conversion to oxalate.
• Symptoms of PH1: Patients may present with recurrent kidney stones, nephrocalcinosis (calcium deposits in the kidneys), and renal insufficiency.
• Diagnosis and Treatment: Diagnosis of PH1 involves genetic testing for mutations in the AGXT gene. Treatment options include high fluid intake, vitamin B6 (pyridoxine) supplements to enhance residual AGXT activity, dietary modifications, and in severe cases, liver and kidney transplantation.

Summary:

AGXT (alanine glyoxylate aminotransferase) is a crucial liver enzyme involved in glyoxylate metabolism. It converts glyoxylate to glycine, preventing the formation of oxalate and subsequent kidney stones. Mutations in the AGXT gene can lead to primary hyperoxaluria type 1 (PH1), a severe metabolic disorder characterized by excessive oxalate production and renal complications. Understanding AGXT's function and its role in PH1 is vital for developing effective diagnostic and therapeutic strategies for affected individuals