9hjn

Structural highlights

Disease

GALE_HUMAN Defects in GALE are the cause of epimerase-deficiency galactosemia (EDG) [MIM:230350; also known as galactosemia type 3. Clinical features include early-onset cataracts, liver damage, deafness and mental retardation. There are two clinically distinct forms of EDG. (1) A benign, or 'peripheral' form with no detectable GALE activity in red blood cells and characterized by mild symptoms. Some patients may suffer no symptoms beyond raised levels of galactose-1-phosphate in the blood. (2) A much rarer 'generalized' form with undetectable levels of GALE activity in all tissues and resulting in severe features such as restricted growth and mental development.^{[1] [2] [3] [4] [5] [6] [7] [8]}

Function

GALE_HUMAN Catalyzes two distinct but analogous reactions: the epimerization of UDP-glucose to UDP-galactose and the epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine.

References

1. ↑ Timson DJ. Functional analysis of disease-causing mutations in human UDP-galactose 4-epimerase. FEBS J. 2005 Dec;272(23):6170-7. PMID:16302980 doi:10.1111/j.1742-4658.2005.05017.x
2. ↑ Maceratesi P, Daude N, Dallapiccola B, Novelli G, Allen R, Okano Y, Reichardt J. Human UDP-galactose 4' epimerase (GALE) gene and identification of five missense mutations in patients with epimerase-deficiency galactosemia. Mol Genet Metab. 1998 Jan;63(1):26-30. PMID:9538513 doi:S1096-7192(97)92645-7
3. ↑ Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM. Molecular basis for severe epimerase deficiency galactosemia. X-ray structure of the human V94m-substituted UDP-galactose 4-epimerase. J Biol Chem. 2001 Jun 8;276(23):20617-23. Epub 2001 Mar 7. PMID:11279193 doi:10.1074/jbc.M101304200
4. ↑ Quimby BB, Alano A, Almashanu S, DeSandro AM, Cowan TM, Fridovich-Keil JL. Characterization of two mutations associated with epimerase-deficiency galactosemia, by use of a yeast expression system for human UDP-galactose-4-epimerase. Am J Hum Genet. 1997 Sep;61(3):590-8. PMID:9326324 doi:S0002-9297(07)64322-5
5. ↑ Wohlers TM, Christacos NC, Harreman MT, Fridovich-Keil JL. Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia. Am J Hum Genet. 1999 Feb;64(2):462-70. PMID:9973283 doi:S0002-9297(07)61751-0
6. ↑ Henderson JM, Huguenin SM, Cowan TM, Fridovich-Keil JL. A PCR-based method for detecting known mutations in the human UDP galactose-4'-epimerase gene associated with epimerase-deficiency galactosemia. Clin Genet. 2001 Nov;60(5):350-5. PMID:11903335
7. ↑ Park HD, Park KU, Kim JQ, Shin CH, Yang SW, Lee DH, Song YH, Song J. The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia in Korean patients. Genet Med. 2005 Nov-Dec;7(9):646-9. PMID:16301867 doi:10.109701.gim.0000194023.27802.2d
8. ↑ Wasilenko J, Lucas ME, Thoden JB, Holden HM, Fridovich-Keil JL. Functional characterization of the K257R and G319E-hGALE alleles found in patients with ostensibly peripheral epimerase deficiency galactosemia. Mol Genet Metab. 2005 Jan;84(1):32-8. PMID:15639193 doi:S1096-7192(04)00242-2