Адам ағзасындағы галактоза метаболизміне жауапты GALT ферменті

Mammalian protein found in Homo sapiens

Galactose 1 phosphate uridyltransferase (or GALT, G1PUT) is an enzyme responsible for converting ingested galactose to glucose. Galactose 1 phosphate uridyltransferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, namely:
UDP glucose + galactose 1 phosphate glucose 1 phosphate + UDP galactose
The expression of GALT is controlled by the actions of the FOXO3 gene. The absence of this enzyme results in classic galactosemia in humans and can be fatal in the newborn period if lactose is not removed from the diet. The pathophysiology of galactosemia has not been clearly defined. This means that the net reaction consists of two reactants and two products (see the reaction above) and it proceeds by the following mechanism: the enzyme reacts with one substrate to generate one product and a modified enzyme, which goes on to react with the second substrate to make the second product while regenerating the original enzyme. In the case of GALT, the His166 residue acts as a potent nucleophile to facilitate transfer of a nucleotide between UDP hexoses and hexose 1 phosphates. UDP glucose + E His Glucose 1 phosphate + E His UMP
Galactose 1 phosphate + E His UMP UDP galactose + E His]]

The three dimensional structure at 180 pm resolution (x ray crystallography) of GALT was determined by Wedekind, Frey, and Rayment, and their structural analysis found key amino acids essential for GALT function. GALT also has minimal (~0.1%) GalNAc transferase activity. X ray crystallography revealed that the side chain of Tyr289 forms a hydrogen bond with the N acetyl group of UDP GalNAc. Point mutation of residue Tyr289 to Leu, Ile, or Asn eliminates this interaction, enhancing GalNAc transferase activity, with the Y289L mutation showing comparable GalNAc transferase activity as the wild type enzyme's Gal transferase activity.

Deficiency of GALT causes classic galactosemia. Galactosemia is an autosomal recessive inherited disorder detectable in newborns and childhood. It occurs at approximately 1 in every 40,000 60,000 live born infants. Classical galactosemia (G/G) is caused by a deficiency in GALT activity, whereas the more common clinical manifestations, Duarte (D/D) and the Duarte/Classical variant (D/G) are caused by the attenuation of GALT activity. Symptoms include ovarian failure, developmental coordination disorder (difficulty speaking correctly and consistently), and neurologic deficits. For example, a single mutation from A to G in exon 6 of the GALT gene changes Glu188 to an arginine and a mutation from A to G in exon 10 converts Asn314 to an aspartic acid. However, those afflicted with galactosemia can live relatively normal lives by avoiding milk products and anything else containing galactose (because it cannot be metabolized), but there is still the potential for problems in neurological development or other complications, even in those who avoid galactose.