galactose-1-phosphate uridyltransferase

ガラクトース-1-リン酸ウリジルトランスフェラーゼ

関

UTP-hexose-1-phosphate uridylyltransferase

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

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）』「2016/02/27 17:04:04」(JST)

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[Wiki en表示]

Galactose-1-phosphate uridylyltransferase
Cartoon diagram of an E. coli GALT dimer in complex with UDP-galactose. From PDB: 1GUP​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1R3A​
Identifiers
Symbol	GALT
External IDs	OMIM: 606999 MGI: 95638 HomoloGene: 126 GeneCards: GALT Gene
EC number	2.7.7.12
Gene ontology Molecular function • protein binding • UDP-glucose:hexose-1-phosphate uridylyltransferase activity • zinc ion binding Cellular component • Golgi apparatus • cytosol Biological process • carbohydrate metabolic process • galactose metabolic process • UDP-glucose catabolic process • galactose catabolic process • small molecule metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2592	14430
Ensembl	ENSG00000213930	ENSMUSG00000036073
UniProt	P07902	Q03249
RefSeq (mRNA)	NM_000155	NM_001302511
RefSeq (protein)	NP_000146	NP_001289440
Location (UCSC)	Chr 9: 34.64 – 34.65 Mb	Chr 4: 41.76 – 41.76 Mb
PubMed search	[1]	[2]

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 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 1.8 angstrom 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：マネージメントおよび転帰 galactosemia management and outcome
• 2. ガラクトース血症：臨床的特徴および診断 galactosemia clinical features and diagnosis
• 3. 関節リウマチの病因 pathogenesis of rheumatoid arthritis
• 4. 小児における慢性下痢の原因の概要 overview of the causes of chronic diarrhea in children
• 5. 肝臓の有機アニオン輸送能および薬物代謝能の検査 tests of the livers capacity to transport organic anions and metabolize drugs

English Journal

• Endogenous galactose formation in galactose-1-phosphate uridyltransferase deficiency.

• Schadewaldt P1, Kamalanathan L, Hammen HW, Kotzka J, Wendel U.
• Archives of physiology and biochemistry.Arch Physiol Biochem.2014 Dec;120(5):228-39. doi: 10.3109/13813455.2014.962547. Epub 2014 Sep 30.
• Abstract Patients with classical galactosaemia (galactose-1-phosphate uridyltransferase (GALT) deficiency) manifest clinical complications despite strict dietary galactose restriction. Therefore the significance of endogenous galactose production has been assessed. Previous in vivo studies primarily
• PMID 25268296

• Altered synaptic architecture and glycosylated synaptomatrix composition in a Drosophila classic galactosemia disease model.

• Jumbo-Lucioni P1, Parkinson W1, Broadie K2.
• Disease models & mechanisms.Dis Model Mech.2014 Oct 17. pii: dmm.017137. [Epub ahead of print]
• Classic galactosemia (CG) is an autosomal recessive disorder resulting from loss of galactose-1-phosphate uridyltransferase (GALT) that catalyzes conversion of galactose-1-phosphate and uridine diphosphate (UDP)-glucose to glucose-1-phosphate and UDP-galactose, immediately upstream of UDP-N-acetylga
• PMID 25326312

• Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity.

• Choi R, Jo KI, Ko DH, Lee DH, Song J, Jin DK, Ki CS, Lee SY, Kim JW, Lee YW1, Park HD.
• BMC medical genetics.BMC Med Genet.2014 Aug 15;15:94. doi: 10.1186/s12881-014-0094-5.
• BACKGROUND: Classic galactosemia (OMIM #230400) is an autosomal recessive metabolic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) protein due to mutations in the GALT gene. The aim of this study was to provide a comprehensive and updated mutation s
• PMID 25124065

Japanese Journal

• Improved isoelectric focusing of normal and variant forms of erythrocyte galactose-1-phosphate uridyltransferase.

• VACCARO AM.
• Electrophoresis 3, 58-61, 1982
• NAID 80001207207

• Pyrophosphorylase Activities towards Nucleoside Diphosphate Sugars in Bifidobacterium bifidum : Biochemical studies on Bifidobacterium bifidum(I)

• TOCHIKURA TATSUROKURO,LEE LYANG JA,KIMURA AKIRA
• Journal of fermentation technology 55(2), 122-129, 1977-04-25
• … The cell-free extract of Bifidobacterium bifidum grown on glucose, lactose, or galactose as a carbon source showed relatively high pyrophosphorylase activities towatds uridine diphosphate glucose (UDP-glucose) and uridine diphosphate galactose(UDP-galactose) and a slight activity towards uridine diphosphate xylose(UDP-xylose). …
• NAID 110002672392

• A method for galactose-1-phosphate uridyltransferase assay and the separation of its isozymes by DEAE-cellulose column chromatography.

• SHIN-BUHRING Y.
• Clinica Chimica Acta 70, 371-377, 1976
• NAID 30003260898

Related Links

• Galactose—1-phosphate uridylyltransferase - Wikipedia, the free ...

Galactose-1-phosphate uridylyltransferase (or GALT) is an enzyme (EC 2.7.7.12) responsible for converting ingested galactose ... Galactose-1-phosphate uridylyltransferase (GALT) catalyzes the second step of the Leloir pathway of galactose ...

Related Pictures

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★リンクテーブル★

リンク元	「解糖系」「代謝系」「UTP-hexose-1-phosphate uridylyltransferase」
関連記事	「phosphate」「galactose」

「解糖系」

　　[★]

英

glycolytic pathway

同

エムデン-マイヤーホフ経路 Embden-Meyerhof pathway

関

解糖、TCA回路

• CH(OH)-CH(OH)-C(OH)H-CH(OH)-C(CH2OH)H-O- グルコース (OHが↓↓↑↓↑)
• CH(OH)-CH(OH)-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- グルコース-6-リン酸 (OHが↓↓↑↓↑)
• C(CH2OH)OH-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- フルクトース-6-リン酸
• C(CH2O-PO3)OH-C(OH)H-CH(OH)-C(CH2O-PO3)H-O- フルクトース-1,6-リン酸

glucose
↓-hexokinase/glucokinase(liver)
glucose 6-phosphate
↓-phosphohexose isomerase
fructose 6-phosphate
↓-phosphofructokinase
fructose 1,6-bisphosphate
↓-aldolase
glyceraldehyde 3-phosphate
↓-glyceraldehyde-3-phosphate dehydrogenase
1,3-bisphosphoglycerate
↓-phosphoglycerate kinase →ATP
3-phosphoglycerate
↓-phosphoglyceate mutase
2-phosphoglycerate
↓-enolase
phosphoenolpyruvate
↓-pyruvate kinase → ATP
pyruvate
　－(pyruvate dehydrogenase)→acetyl-CoA
　－(pyruvate carboxylase)→oxaloacetate－(NADH+H+)→malate

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解糖系の酵素 (first aid step1 2006 p.87, FASTEP1_87_酵素一覧.xls)

1	galactokinase	キナーゼ
2	galactose-1-phosphate uridyltransferase	転移酵素
3	hexokinase/glucokinase	キナーゼ
4	glucose-6-phosphatase	ホスファターゼ
5	glucose-6-phosphate dehydrogenase	脱水素酵素
6	transketolase
7	phosphofructokinase	キナーゼ
8	fructose-1,6-bisphosphatase	ホスファターゼ
9	fructokinase	キナーゼ	フルクトキナーゼ
10	aldolase B		アルドラーゼ
11	pyruvate kinase	キナーゼ	ピルビン酸キナーゼ
12	pyruvate dehydrogenase	脱水素酵素	ピルビン酸デヒドロゲナーゼ
13	HMG-CoA reductase	還元酵素	HMG-CoA還元酵素
14	pyruvate carboxylase	カルボキシラーゼ	ピルビン酸カルボキシラーゼ
15	PEP carboxykinase	キナーゼ	PEPカルボキシキナーゼ
16	citrate synthase	合成酵素	クエン酸合成酵素
17	α-ketoglutarate dehydrogenase	脱水素酵素	α-ケトグルタミン酸脱水素酵素
18	ornithine transcarbamylase	転移酵素	オルニチンカルバモイルトランスフェラーゼ

「代謝系」

　　[★]

英

metabolic pathway

関

代謝経路

• 解糖系
• TCA回路
• 電子伝達系
• 尿酸回路
• 糖新生経路

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• 1 galactokinase
• 2 galactose-1-phosphate uridyltransferase
• 3 hexokinase/glucokinase
• 4 glucose-6-phosphatase
• 5 glucose-6-phosphate dehydrogenase
• 6 transketolase
• 7 phosphofructokinase
• 8 fructose-1,6-bisphosphatase
• 9 fructokinase
• 10 aldolase B
• 11 pyruvate kinase
• 12 pyruvate dehydrogenase
• 13 HMG-CoA reductase
• 14 pyruvate carboxylase
• 15 PEP carboxykinase
• 16 citrate synthase
• 17 α-ketoglutarate dehydrogenase
• 18 ornithine transcarbamylase

「UTP-hexose-1-phosphate uridylyltransferase」

　　[★]

UTPヘキソース-1-リン酸ウリジリルトランスフェラーゼ

関

galactose-1-phosphate uridyltransferase

「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

　 　 　

「galactose」

　　[★]

ガラクトース

関

D-galactose、gal、galactopyranose、galactopyranoside