Defective GALE does not epimerise UDP-Gal to UDP-Glc

Stable Identifier
R-HSA-5610036
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Cytosolic UDP galactose 4 epimerase (GALE) catalyses the interconversion of UDP-D-galactose (UDP-Gal) and UDP-D-glucose (UDP-Glc), the third reacton in the Leloir pathway of galactose metabolism. GALE can also catalyse the epimerisation of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The active form of the enzyme is a homodimer with one molecule of bound NAD+ per monomer (GALE:NAD+ dimer). Defects in GALE can cause Epimerase deficiency galactosemia (EDG; MIM:230350), or type III galactosemia (diseases of galactose metabolism) whose clinical features include early onset cataracts, liver damage, deafness and mental retardation. The disease is now considered to be a continuum from mild to severe phenotypes (Openo et al. 2006). A mutation causing the severe form of EDG is V94M (Wohlers et al. 1999). Protein misfolding is the underlying cause of the disease and this leads to loss of enzymatic activity and, in some cases, reduced affinity for the NAD+ cofactor (McCorvie et al. 2012).

Literature References
PubMed ID Title Journal Year
22613355 Altered cofactor binding affects stability and activity of human UDP-galactose 4'-epimerase: implications for type III galactosemia

McCorvie, TJ, Liu, Y, Frazer, A, Gleason, TJ, Fridovich-Keil, JL, Timson, DJ

Biochim. Biophys. Acta 2012
16385452 Epimerase-deficiency galactosemia is not a binary condition

Openo, KK, Schulz, JM, Vargas, CA, Orton, CS, Epstein, MP, Schnur, RE, Scaglia, F, Berry, GT, Gottesman, GS, Ficicioglu, C, Slonim, AE, Schroer, RJ, Yu, C, Rangel, VE, Keenan, J, Lamance, K, Fridovich-Keil, JL

Am. J. Hum. Genet. 2006
9973283 Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia

Wohlers, TM, Christacos, NC, Harreman, MT, Fridovich-Keil, JL

Am. J. Hum. Genet. 1999
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
UDP-glucose 4-epimerase activity of GALE V94M:GALE V94M:NAD+:NAD+ [cytosol]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
galactosemia 9870 Galactose intolerance, Galactosaemia
Authored
Reviewed
Created
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