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Definition of AGXT

< b>AGXT: A gene that provides instructions for making a liver enzyme called alanine-glyoxylate aminotransferase (AGXT). Inside liver cells, this enzyme is found in peroxisomes, structures that contain many different enzymes used to produce energy and the basic materials important for cellular activities. AGXT converts a compound called glyoxylate to glycine, an amino acid that is a building block for making enzymes and other proteins.

More than 40 AGXT mutations responsible for a disease called type 1 primary hyperoxaluria have been identified. In about two-thirds of type 1 primary hyperoxaluria cases, AGXT enzyme activity is partially or entirely absent because of a mutation. As a result of this enzyme shortage, glyoxylate accumulates and is converted to a compound called oxalate instead of glycine. Oxalate, in turn, combines with calcium to form calcium oxalate, which the body cannot readily eliminate. Deposits of calcium oxalate can lead to kidney stones, kidney damage or failure, and injury to other organs, which are characteristic features of primary hyperoxaluria.

In about one-third of people with type 1 primary hyperoxaluria, the AGXT enzyme is misplaced within the cell. Misplacement happens when certain mutations occur with a natural variation (polymorphism) in the gene. In most cases, a mutation replaces the amino acid glycine with arginine at position 170 in the enzyme's chain of amino acids (also written as Gly170Arg). The mutation is found with a polymorphism that replaces the amino acid proline with leucine at position 11 (or Pro11Leu). The combined effect of the mutation and the polymorphism alters the structure of AGXT and changes the cellular shipping address of the enzyme. Instead of locating in peroxisomes, the enzyme is misdelivered to mitochondria, the energy-producing centers of cells. Even though the enzyme retains some of its activity, it cannot make contact with glyoxylate, which is located in peroxisomes. As a result, glyoxylate accumulates, leading to the signs and symptoms of primary hyperoxaluria. The AGXT gene is located on the long (q) arm of chromosome 2 in 2q36-q37. See: hyperoxaluria.