Galactose-1-phosphate uridylyltransferase
GALT | |||
---|---|---|---|
Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
---|---|---|---|---|---|---|---|---|---|
UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) |
| ||||||||
Location (UCSC) | Chr 9: 34.64 – 34.65 Mb | Chr 4: 41.76 – 41.76 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Galactose-1-phosphate uridyl transferase, N-terminal domain | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | GalP_UDP_transf | ||||||||
SCOP2 | 1hxp / SCOPe / SUPFAM | ||||||||
|
Galactose-1-phosphate uridyl transferase, C-terminal domain | |||||||||
---|---|---|---|---|---|---|---|---|---|
|
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
- UDP-glucose + galactose 1-phosphateUDP-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
- UDP-glucose + E-His ⇌ Glucose-1-phosphate + E-His-UMP
- Galactose-1-phosphate + E-His-UMP ⇌ UDP-galactose + E-His[8]
Structural studies
The three-dimensional structure at 180
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
Disease database
Galactosemia (GALT) Mutation Database
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000213930 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036073 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: GALT galactose-1-phosphate uridylyltransferase".
- PMID 4606575.
- ^ "Double displacement mechanism - Definition". Archived from the original on 2016-03-03. Retrieved 2010-05-19.
- ^ PMID 7669762.
- ^ "Untitled Document". Archived from the original on 2008-12-04. Retrieved 2010-05-19.
- PMID 10220154.
- PMID 11916963.
- ^ S2CID 32233614.
- ^ S2CID 11937698.
- ^ "Apraxia of Speech". Archived from the original on 2006-02-28. Retrieved 2010-05-19.
- PMID 12552079.
- PMID 19859980.
- ^ "Galactosemia - Treatment". Archived from the original on 2002-08-28.
Further reading
- Reichardt JK (1993). "Genetic basis of galactosemia". Human Mutation. 1 (3): 190–6. S2CID 504197.
- Tyfield L, Reichardt J, Fridovich-Keil J, Croke DT, Elsas LJ, Strobl W, Kozak L, Coskun T, Novelli G, Okano Y, Zekanowski C, Shin Y, Boleda MD (1999). "Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene". Human Mutation. 13 (6): 417–30. S2CID 34860932.
- Reichardt JK, Belmont JW, Levy HL, Woo SL (March 1992). "Characterization of two missense mutations in human galactose-1-phosphate uridyltransferase: different molecular mechanisms for galactosemia". Genomics. 12 (3): 596–600. PMID 1373122.
- Leslie ND, Immerman EB, Flach JE, Florez M, Fridovich-Keil JL, Elsas LJ (October 1992). "The human galactose-1-phosphate uridyltransferase gene". Genomics. 14 (2): 474–80. PMID 1427861.
- Reichardt JK, Levy HL, Woo SL (June 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. PMID 1610789.
- Reichardt JK, Packman S, Woo SL (October 1991). "Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase". American Journal of Human Genetics. 49 (4): 860–7. PMID 1897530.
- Reichardt JK, Woo SL (April 1991). "Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase". Proceedings of the National Academy of Sciences of the United States of America. 88 (7): 2633–7. PMID 2011574.
- Flach JE, Reichardt JK, Elsas LJ (August 1990). "Sequence of a cDNA encoding human galactose-1-phosphate uridyl transferase". Molecular Biology & Medicine. 7 (4): 365–9. PMID 2233247.
- Reichardt JK, Berg P (April 1988). "Cloning and characterization of a cDNA encoding human galactose-1-phosphate uridyl transferase". Molecular Biology & Medicine. 5 (2): 107–22. PMID 2840550.
- Bergren WG, Donnell GN (July 1973). "A new variant of galactose-1-phosphate uridyltransferase in man: the Los Angeles variant". Annals of Human Genetics. 37 (1): 1–8. S2CID 22699183.
- Shih LY, Suslak L, Rosin I, Searle BM, Desposito F (November 1984). "Gene dosage studies supporting localization of the structural gene for galactose-1-phosphate uridyl transferase (GALT) to band p13 of chromosome 9". American Journal of Medical Genetics. 19 (3): 539–43. PMID 6095663.
- Ashino J, Okano Y, Suyama I, Yamazaki T, Yoshino M, Furuyama J, Lin HC, Reichardt JK, Isshiki G (1995). "Molecular characterization of galactosemia (type 1) mutations in Japanese". Human Mutation. 6 (1): 36–43. S2CID 23500152.
- Elsas LJ, Langley S, Paulk EM, Hjelm LN, Dembure PP (1995). "A molecular approach to galactosemia". European Journal of Pediatrics. 154 (7 Suppl 2): S21-7. S2CID 11937698.
- Elsas LJ, Langley S, Steele E, Evinger J, Fridovich-Keil JL, Brown A, Singh R, Fernhoff P, Hjelm LN, Dembure PP (March 1995). "Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes". American Journal of Human Genetics. 56 (3): 630–9. PMID 7887416.
- Fridovich-Keil JL, Langley SD, Mazur LA, Lennon JC, Dembure PP, Elsas JL (March 1995). "Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family". American Journal of Human Genetics. 56 (3): 640–6. PMID 7887417.
- Davit-Spraul A, Pourci ML, Ng KH, Soni T, Lemonnier A (November 1994). "Regulatory effects of galactose on galactose-1-phosphate uridyltransferase activity on human hepatoblastoma HepG2 cells". FEBS Letters. 354 (2): 232–6. S2CID 45242645.
- Lin HC, Kirby LT, Ng WG, Reichardt JK (February 1994). "On the molecular nature of the Duarte variant of galactose-1-phosphate uridyl transferase (GALT)". Human Genetics. 93 (2): 167–9. S2CID 42558872.
- Elsas LJ, Dembure PP, Langley S, Paulk EM, Hjelm LN, Fridovich-Keil J (June 1994). "A common mutation associated with the Duarte galactosemia allele". American Journal of Human Genetics. 54 (6): 1030–6. PMID 8198125.
- Reichardt JK, Novelli G, Dallapiccola B (March 1993). "Molecular characterization of the H319Q galactosemia mutation". Human Molecular Genetics. 2 (3): 325–6. PMID 8499924.
External links
- Galactose-1-P-Uridyltransferase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- GeneReviews/NIH/NCBI/UW entry on Galactosemia
- Galactosemia (GALT) Mutation Database
- GALT Protein Database
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Galactose-1-phosphate uridylyltransferase