AGXT

AGXT Full Name

alanine-glyoxylate aminotransferase

AGXT Introduction

AGXT (alanine-glyoxylate aminotransferase) is a liver-specific peroxisomal enzyme that plays a central role in human glyoxylate metabolism. It catalyzes the transamination of glyoxylate to glycine using L-alanine as the amino donor, generating pyruvate in parallel. This reaction is critically important for preventing the accumulation of glyoxylate, which otherwise is converted to oxalate — a toxic end product that leads to calcium oxalate crystal deposition in the kidneys and urinary tract. AGXT belongs to the Class‑I pyridoxal‑5′-phosphate (PLP)-dependent aminotransferase family and is predominantly expressed in hepatocyte peroxisomes. Mutations in the AGXT gene cause Primary Hyperoxaluria Type I (PH1), the most severe and common form of primary hyperoxaluria, leading to recurrent nephrolithiasis, nephrocalcinosis, and often end-stage renal disease.

Figure 1. Schematic structure and metabolic function of AGXT.

Biochemical Function and Peroxisomal Localization
Human AGXT is a homodimeric enzyme (each subunit ~43 kDa) that operates with high specificity toward glyoxylate. Under normal physiological conditions, AGXT activity ensures that endogenous glyoxylate — derived from hydroxyproline metabolism, glycolate oxidation, or other pathways — is efficiently converted to glycine, a non‑toxic amino acid used in protein synthesis and glutathione production. In the absence of functional AGXT, glyoxylate accumulates in the cytoplasm and is dehydrogenated by lactate dehydrogenase or glycolate oxidase, yielding oxalate. Oxalate has no known beneficial metabolic role; it binds calcium ions to form insoluble calcium oxalate crystals, which deposit in the renal tubules, leading to progressive interstitial fibrosis, nephrocalcinosis, and eventual kidney failure. AGXT is encoded by a single gene on chromosome 2q37.3 and its expression is highly restricted to the liver, although trace activity can be observed in the pancreas and kidney.

Clinical Significance of AGXT Mutations
Pathogenic mutations in the AGXT gene are the exclusive genetic cause of primary hyperoxaluria type 1 (PH1), an autosomal recessive inherited disorder characterized by systemic oxalate overload. Loss - of - function, misfolding, or mitochondrial mistargeting of AGXT protein leads to impaired glyoxylate detoxification, resulting in excessive oxalate synthesis, hyperoxaluria, and progressive deposition of calcium oxalate crystals in the kidneys, urinary tract, and multiple systemic organs. Clinically, PH1 manifests with recurrent nephrolithiasis, nephrocalcinosis, and early - onset end - stage renal disease (ESRD) in children and young adults; systemic oxalosis can cause severe damage to the heart, retina, bone, and central nervous system. The worldwide incidence of AGXT - related PH1 is estimated at approximately 1 in 100,000–120,000 individuals, accounting for more than 70% of all primary hyperoxaluria cases. Beyond classic PH1, partial AGXT deficiency and mild allelic variants are associated with idiopathic calcium oxalate stones, chronic kidney disease, and hepatic metabolic disturbances, highlighting the broad clinical impact of AGXT dysfunction.

Alternate Names for AGXT

AGXT; alanine-glyoxylate aminotransferase; SPAT; serine--pyruvate aminotransferase; AGT; AGT1; AGXT1; glycolicaciduria; L alanine: glyoxylate aminotransferase 1; oxalosis I