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Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Galactose-1-phosphate uridyl transferase, N-terminal domain
Galactose-1-phosphate uridyl transferase, N-terminal domain
Identifiers
Symbol	GalP_UDP_transf
Pfam	PF01087
Pfam clan	CL0265
PROSITE	PDOC00108
SCOP2	1hxp / SCOPe / SUPFAM
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

GALT
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	5IN3
Identifiers
Aliases	GALT, entrez:2592, galactose-1-phosphate uridylyltransferase
External IDs	OMIM: 606999; MGI: 95638; HomoloGene: 126; GeneCards: GALT; OMA:GALT - orthologs
Gene location (Human)
Chr.	Chromosome 9 (human)
End	34,651,035 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	41,758,695 bp
RNA expression pattern
	Top expressed in
	right lobe of liver; ; right adrenal gland; ; apex of heart; ; right adrenal cortex; ; left adrenal cortex; ; right lobe of thyroid gland; ; granulocyte; ; right ovary; ; anterior pituitary; ; left lobe of thyroid gland;
	Top expressed in
	superior frontal gyrus; ; Cerebellum; ; cerebellar cortex; ; renal cortex; ; proximal tubule; ; primary visual cortex; ; striatum of neuraxis; ; right kidney; ; heart; ; adrenal gland;
	More reference expression data
	n/a
Gene ontology
Molecular function	transferase activity; nucleotidyltransferase activity; protein binding; metal ion binding; UDP-glucose:hexose-1-phosphate uridylyltransferase activity; zinc ion binding;
Cellular component	cytosol; Golgi apparatus; cytoplasm;
Biological process	UDP-glucose catabolic process; galactose catabolic process; galactose catabolic process via UDP-galactose; UDP-glucose metabolic process; galactose metabolic process; carbohydrate metabolic process;
	Sources:Amigo / QuickGO
Orthologs
	2592
	14430
	ENSG00000213930
	ENSMUSG00000036073
	P07902
	Q03249
	NM_001258332; NM_000155; NM_147131; NM_147132
	NM_016658; NM_001302511
	NP_000146; NP_001245261
NP_001289440; NP_057867; NP_001356064; NP_001356069; NP_001356070;
	NP_001356071; NP_001356072; NP_001356073; NP_001356076; NP_001382559
	Wikidata
View/Edit Human	View/Edit Mouse

Galactose-1-phosphate uridyl transferase, C-terminal domain

structure of nucleotidyltransferase complexed with udp-galactose

Identifiers

Symbol

GalP_UDP_tr_C

Pfam clan

1hxp / SCOPe / SUPFAM

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Galactose-1-phosphate uridyltransferase (or GALT, G1PUT) is an enzyme (EC 2.7.7.12) responsible for converting ingested galactose to glucose.^[5]

Galactose-1-phosphate uridyltransferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, namely:

UDP-glucose + galactose 1-phosphate

\rightleftharpoons

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.^[5]

Mechanism

GALT catalyzes the second reaction of the Leloir pathway of galactose metabolism through ping pong bi-bi kinetics with a double displacement mechanism.^[6] 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.^[7] 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.^[8]

UDP-glucose + E-His ⇌ Glucose-1-phosphate + E-His-UMP
Galactose-1-phosphate + E-His-UMP ⇌ UDP-galactose + E-His^[8]

Two-step action of galactose-1-phosphate uridylyltransferase. Image adapted from ^[9]

Structural studies

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.^[8] Among these are Leu4, Phe75, Asn77, Asp78, Phe79, and Val108, which are consistent with residues that have been implicated both in point mutation experiments as well as in clinical screening that play a role in human galactosemia.^[8]^[10]

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.^[11]

Clinical significance

Deficiency of GALT causes classic galactosemia. Galactosemia is an autosomal recessive inherited disorder detectable in newborns and childhood.^[12] 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.^[13] Symptoms include ovarian failure, developmental coordination disorder (difficulty speaking correctly and consistently),^[14] and neurologic deficits.^[13] A single mutation in any of several base pairs can lead to deficiency in GALT activity.^[15] 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.^[13] These two mutations also add new restriction enzyme cut sites, which enable detection by and large-scale population screening with PCR (polymerase chain reaction).^[13] Screening has mostly eliminated neonatal death by G/G galactosemia, but the disease, due to GALT’s role in the biochemical metabolism of ingested galactose (which is toxic when accumulated) to the energetically useful glucose, can certainly be fatal.^[12]^[16] 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.^[17]