galactose-1-phosphate uridylyltransferase galactose-1-phosphate uridylyltransferase galactose-1-phosphate uridylyltransferase (or galt, g1put) is an enzyme (ec 2.7.7.12) responsible for converting ingested galactose to glucose. galtavailable structurespdbortholog search: pdbe rcsb list of pdb id codes5in3identifiersaliasesgalt, entrez:2592, galactose-1-phosphate uridylyltransferaseexternal idsomim: 606999 mgi: 95638 homologene: 126 genecards: galt gene location (human)chr.chromosome 9 (human)band9p13.3start34,638,133 bpend34,651,035 bpgene location (mouse)chr.chromosome 4 (mouse)band4 a5|4 22.07 cmstart41,755,228 bpend41,758,695 bprna expression patternbgeehumanmouse (ortholog)top expressed inright lobe of liverright adrenal glandright lobe of thyroid glandanterior pituitaryleft lobe of thyroid glandright coronary arterytibial nerveright uterine tubeleft uterine tubespleentop expressed insuperior frontal gyruscerebellumcerebellar cortexrenal cortexproximal tubuleheartadrenal glandmuscle tissuekidneyolfactory bulbmore reference expression databiogpsn/agene ontologymolecular 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 / quickgoorthologsspecieshumanmouseentrez259214430ensemblensg00000213930ensmusg00000036073uniprotp07902q03249refseq (mrna)nm_001258332nm_000155nm_147131nm_147132nm_016658nm_001302511refseq (protein)np_000146np_001245261np_001289440np_057867np_001356064np_001356069np_001356070np_001356071np_001356072np_001356073np_001356076np_001382559location (ucsc)chr 9: 34.64 – 34.65 mbchr 4: 41.76 – 41.76 mbpubmed searchwikidataview/edit humanview/edit mouse galactose-1-phosphate uridyl transferase, n-terminal domainidentifierssymbolgalp_udp_transfpfampf01087pfam clancl0265prositepdoc00108scop21hxp / scope / supfamavailable protein structures:pfam structures / ecod pdbrcsb pdb; pdbe; pdbjpdbsumstructure summary galactose-1-phosphate uridyl transferase, c-terminal domainstructure of nucleotidyltransferase complexed with udp-galactoseidentifierssymbolgalp_udp_tr_cpfampf02744pfam clancl0265interproipr005850prositepdoc00108scop21hxp / scope / supfamavailable protein structures:pfam structures / ecod pdbrcsb pdb; pdbe; pdbjpdbsumstructure summary galactose-1-phosphate uridylyltransferase (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. galactose glucose mechanism galt catalyzes the second reaction of the leloir pathway of galactose metabolism through ping pong bi-bi kinetics with a double displacement mechanism. 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 two-step action of galactose-1-phosphate uridylyltransferase. image adapted from 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. 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. clinical significance 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. a single mutation in any of several base pairs can lead to deficiency in galt activity. 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. these two mutations also add new restriction enzyme cut sites, which enable detection by and large-scale population screening with pcr (polymerase chain reaction). 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. 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. disease database galactosemia (galt) mutation database