galactose-1-phosphate uridyl transferase

ガラクトース-1-リン酸ウリジルトランスフェラーゼ GALT

WordNet

1. a salt of phosphoric acid (同)orthophosphate, inorganic_phosphate
2. carbonated drink with fruit syrup and a little phosphoric acid
3. a simple sugar found in lactose (同)brain sugar
4. any of various enzymes that move a chemical group from one compound to another compound

PrepTutorEJDIC

1. 〈U〉リン酸塩 / 《複数形で》リン酸肥料
2. ガラクトース(乳糖から得られる六炭糖)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/01/07 15:48:27」(JST)

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GALT
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5IN3
Identifiers
Aliases	GALT, entrez:2592
External IDs	OMIM: 606999 MGI: 95638 HomoloGene: 126 GeneCards: GALT
Gene ontology Molecular function • transferase activity • nucleotidyltransferase activity • zinc ion binding • protein binding • catalytic activity • metal ion binding • UDP-glucose:hexose-1-phosphate uridylyltransferase activity Cellular component • cytosol • Golgi apparatus Biological process • UDP-glucose catabolic process • galactose metabolic process • galactose catabolic process • carbohydrate metabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2592	14430
Ensembl	ENSG00000213930	ENSMUSG00000036073
UniProt	P07902	Q03249
RefSeq (mRNA)	NM_001258332 NM_000155	NM_016658 NM_001302511
RefSeq (protein)	NP_000146 NP_001245261	NP_057867.2
Location (UCSC)	Chr 9: 34.64 – 34.65 Mb	Chr 4: 41.76 – 41.76 Mb
PubMed search
Wikidata
View/Edit Human		View/Edit Mouse

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

Galactose-1-phosphate uridyl transferase, C-terminal domain
structure of nucleotidyltransferase complexed with udp-galactose
Identifiers
Symbol	GalP_UDP_tr_C
Pfam	PF02744
Pfam clan	CL0265
InterPro	IPR005850
PROSITE	PDOC00108
SCOP	1hxp
SUPERFAMILY	1hxp
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Galactose-1-phosphate uridylyltransferase (or GALT) is an enzyme (EC 2.7.7.12) responsible for converting ingested galactose to glucose.

Galactose-1-phosphate uridylyltransferase (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.

• 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 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.

1. UDP-glucose + E-His ⇌ Glucose-1-phosphate + E-His-UMP
2. 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 discovered by Wedekind, Frey, and Rayment, and their structural analysis has found key amino acids essential for GALT function.

The important amino acids that Wedekind et al. found in their structural analysis of GALT, such as Leu4, Phe75, Asn77, Asp78, Phe79, and Val108, are consistent with residues that have been implicated both in point mutation experiments as well as in clinical screening to play a role in human galactosemia.

Clinical significance

Deficiency of GALT causes classic galactosemia. Galactosemia is a childhood disease of hereditary nature. The autosomal recessive trait affects 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 affliction, Duarte/Classica (D/G) arises from 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 amino acids can lead to attenuation or 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 (since it cannot be metabolized), although there is the potential for problems in neurological development, or other complications, even in those who avoid galactose.

Disease Database

Galactosemia (GALT) Mutation Database

References

Further reading

• Reichardt JK (1993). "Genetic basis of galactosemia". Hum. Mutat. 1 (3): 190–6. doi:10.1002/humu.1380010303. PMID 1301925. 
• Tyfield L, Reichardt J, Fridovich-Keil J, et al. (1999). "Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene". Hum. Mutat. 13 (6): 417–30. doi:10.1002/(SICI)1098-1004(1999)13:6<417::AID-HUMU1>3.0.CO;2-0. PMID 10408771. 
• Reichardt JK, Belmont JW, Levy HL, Woo SL (1992). "Characterization of two missense mutations in human galactose-1-phosphate uridyltransferase: different molecular mechanisms for galactosemia". Genomics. 12 (3): 596–600. doi:10.1016/0888-7543(92)90453-Y. PMID 1373122. 
• Leslie ND, Immerman EB, Flach JE, et al. (1992). "The human galactose-1-phosphate uridyltransferase gene". Genomics. 14 (2): 474–80. doi:10.1016/S0888-7543(05)80244-7. PMID 1427861. 
• Reichardt JK, Levy HL, Woo SL (1992). "Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure-function analysis of human galactose-1-phosphate uridyltransferase". Biochemistry. 31 (24): 5430–3. doi:10.1021/bi00139a002. PMID 1610789. 
• Reichardt JK, Packman S, Woo SL (1991). "Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase". Am. J. Hum. Genet. 49 (4): 860–7. PMC 1683190. PMID 1897530. 
• Reichardt JK, Woo SL (1991). "Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase". Proc. Natl. Acad. Sci. U.S.A. 88 (7): 2633–7. doi:10.1073/pnas.88.7.2633. PMC 51292. PMID 2011574. 
• Flach JE, Reichardt JK, Elsas LJ (1990). "Sequence of a cDNA encoding human galactose-1-phosphate uridyl transferase". Mol. Biol. Med. 7 (4): 365–9. PMID 2233247. 
• Reichardt JK, Berg P (1988). "Cloning and characterization of a cDNA encoding human galactose-1-phosphate uridyl transferase". Mol. Biol. Med. 5 (2): 107–22. PMID 2840550. 
• Bergren WG, Donnell GN (1974). "A new variant of galactose-1-phosphate uridyltransferase in man: the Los Angeles variant". Ann. Hum. Genet. 37 (1): 1–8. doi:10.1111/j.1469-1809.1973.tb01808.x. PMID 4759900. 
• Shih LY, Suslak L, Rosin I, et al. (1985). "Gene dosage studies supporting localization of the structural gene for galactose-1-phosphate uridyl transferase (GALT) to band p13 of chromosome 9". Am. J. Med. Genet. 19 (3): 539–43. doi:10.1002/ajmg.1320190316. PMID 6095663. 
• Ashino J, Okano Y, Suyama I, et al. (1995). "Molecular characterization of galactosemia (type 1) mutations in Japanese". Hum. Mutat. 6 (1): 36–43. doi:10.1002/humu.1380060108. PMID 7550229. 
• Elsas LJ, Langley S, Paulk EM, et al. (1995). "A molecular approach to galactosemia". Eur. J. Pediatr. 154 (7 Suppl 2): S21–7. doi:10.1007/BF02143798. PMID 7671959. 
• Elsas LJ, Langley S, Steele E, et al. (1995). "Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes". Am. J. Hum. Genet. 56 (3): 630–9. PMC 1801164. PMID 7887416. 
• Fridovich-Keil JL, Langley SD, Mazur LA, et al. (1995). "Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family". Am. J. Hum. Genet. 56 (3): 640–6. PMC 1801186. PMID 7887417. 
• Davit-Spraul A, Pourci ML, Ng KH, et al. (1994). "Regulatory effects of galactose on galactose-1-phosphate uridyltransferase activity on human hepatoblastoma HepG2 cells". FEBS Lett. 354 (2): 232–6. doi:10.1016/0014-5793(94)01133-8. PMID 7957929. 
• Lin HC, Kirby LT, Ng WG, Reichardt JK (1994). "On the molecular nature of the Duarte variant of galactose-1-phosphate uridyl transferase (GALT)". Hum. Genet. 93 (2): 167–9. doi:10.1007/BF00210604. PMID 8112740. 
• Elsas LJ, Dembure PP, Langley S, et al. (1994). "A common mutation associated with the Duarte galactosemia allele". Am. J. Hum. Genet. 54 (6): 1030–6. PMC 1918187. PMID 8198125. 
• Reichardt JK, Novelli G, Dallapiccola B (1993). "Molecular characterization of the H319Q galactosemia mutation". Hum. Mol. Genet. 2 (3): 325–6. doi:10.1093/hmg/2.3.325. PMID 8499924. 

External links

• Galactose-1-P-Uridyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
• GeneReviews/NIH/NCBI/UW entry on Galactosemia
• Galactosemia (GALT) Mutation Database
• GALT Protein Database

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. ガラクトース血症：臨床的特徴および診断galactosemia clinical features and diagnosis [show details]
  … distinct phenotype: Galactose-1-phosphate uridyl transferase (GALT) deficiency – The most common and severe form of galactosemia is caused by deficiency of GALT, the enzyme that converts galactose-1-phosphate …
• 2. ガラクトース血症：マネージメントおよび合併症galactosemia management and complications [show details]
  … rate of endogenous galactose production correlates inversely with age . Because the rate of endogenous production exceeds the amount of galactose in a nondairy diet, elevated galactose levels likely reflect …
• 3. 新生児や乳児に生じる胆汁うっ滞の原因causes of cholestasis in neonates and young infants [show details]
  …the result of galactose-1-phosphate uridyl transferase (GALT) deficiency. Affected infants present with mixed (conjugated and unconjugated) hyperbilirubinemia after the onset of galactose-containing feedings …
• 4. 乳児および小児における低血糖症の原因causes of hypoglycemia in infants and children [show details]
  …defects in the enzymes responsible for converting galactose to glucose in the liver. The most common and severe form is caused by a deficiency of galactose-1-phosphate uridyl transferase (GALT). Individuals …
• 5. 急性リン酸腎症acute phosphate nephropathy [show details]
  …following the use of bowel purgatives that contain oral sodium phosphate (OSP) and has been reported following the administration of sodium phosphate-containing enemas . OSP was formerly sold without prescription …

English Journal

• [Diagnosis of two neonates with galactosemia by using next generation sequencing].

• Zhang H1, Chen D, Liu C, Liu X, Gai Z, Liu Y.
• Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics.Zhonghua Yi Xue Yi Chuan Xue Za Zhi.2018 Apr 10;35(2):248-252. doi: 10.3760/cma.j.issn.1003-9406.2018.02.023.
• PMID 29653003

• Molecular basis and clinical presentation of classic galactosemia in a Croatian population.

• Ramadža DP1, Sarnavka V1, Vuković J1, Fumić K2, Krželj V3, Lozić B3, Pušeljić S4, Pereira H5, Silva MJ5, Tavares de Almeida I5, Barić I1, Rivera I5.
• Journal of pediatric endocrinology & metabolism : JPEM.J Pediatr Endocrinol Metab.2018 Jan 26;31(1):71-75. doi: 10.1515/jpem-2017-0302.
• PMID 29252199

• GALT Deficiency Galactosemia.

• Anderson S1.
• MCN. The American journal of maternal child nursing.MCN Am J Matern Child Nurs.2018 Jan/Feb;43(1):44-51. doi: 10.1097/NMC.0000000000000388.
• PMID 29215423

Japanese Journal

• Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT)

• CRAMER DW
• Mol Hum Reprod 2, 149-152, 1996
• NAID 30024988900

• Vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT)

• CRAMER DW
• Mol. Hum. Reprod. 2, 145-148, 1996
• NAID 30024988899

• Galactose-1-phosphate uridyl transferase欠損によるガラクト-ス白内障の1例

• 早坂 征次 [他]
• 眼科 24(3), p281-283, 1982-03
• NAID 40000531222

Related Links

• Galactose-1-phosphate uridyl transferase - South Tees ...

Background. Galactosemia is an autosomal recessive disorder that results from a deficiency of 1 of the three enzymes catalysing the conversion of galactose to glucose: galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALK), and uridine diphosphate galactose-4-epimerase (GALE). GALT deficiency is the most common cause of galactosemia, ...

• Galactose 1-Phosphate Uridyl Transferase – Supra-Regional ...

Galactose 1-Phosphate Uridyl Transferase Principle Of Method: The enzyme measured catalyses the reaction. Galactose 1-phosphate + UDP-glucose ® UDP-galactose + glucose 1-phosphate Two different assay methods are used, one for red cells and the other for fibroblasts, chorionic villi and amniotic cells.

• Galactose-1-Phosphate Uridyltransferase - an overview ...

Galactosemia is a rare genetic disorder caused by defective galactose-1-phosphate-uridyltransferase ( GALT; EC 2.7.7.12; OMIM 606999) or more rarely by mutations in the genes encoding galactokinase ( GALK; EC604313; OMIM 230200) or UDP-galactose-1,4-epimerase ( GALE; EC606953; OMIM 5.1.3.2). Symptoms in newborns appear within days of milk feedings.

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★リンクテーブル★

リンク元	「GALT」「ガラクトース-1-リン酸ウリジルトランスフェラーゼ」
拡張検索	「galactose-1-phosphate uridyl transferase deficiency」「galactose-1-phosphate uridyl transferase欠損症」
関連記事	「phosphate」「transferase」「galactose」「uridyl transferase」「transferases」

「GALT」

　　[★]

• 腸管関連リンパ組織, gut-associated lymphoid tissue
• ガラクトース-1-リン酸ウリジルトランスフェラーゼ, galactose-1-phosphate uridyl transferase

「ガラクトース-1-リン酸ウリジルトランスフェラーゼ」

　　[★]

英

galactose-1-phosphate uridyl transferase, galactose 1-phosphate uridyl transferase, GALT

関

UTPヘキソース-1-リン酸ウリジリルトランスフェラーゼ

「galactose-1-phosphate uridyl transferase deficiency」

　　[★] ガラクトース-1-リン酸ウリジルトランスフェラーゼ欠損症

「galactose-1-phosphate uridyl transferase欠損症」

　　[★] ガラクトース-1-リン酸ウリジルトランスフェラーゼ欠損症

「phosphate」

　　[★]

• n.

• (化合物)リン酸塩、リン酸エステル、ホスフェート、フォスフェート、リン酸

関

inorganic phosphate、orthophosphate、orthophosphoric acid、phospho、phosphoester、phosphoric、phosphoric acid、phosphoric acid ester、phosphorus

　 　 　

「transferase」

　　[★]

• n.

• トランスフェラーゼ、転移酵素、付加酵素

関

lyase、synthase、transposase

　

「galactose」

　　[★]

ガラクトース

関

D-galactose、gal、galactopyranose、galactopyranoside

　 　

「uridyl transferase」

　　[★]

ウリジルトランスフェラーゼ

関

UDPglucose-hexose-1-phosphate uridylyltransferase

「transferases」

　　[★] トランスフェラーゼ