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

Stable Identifier
Reaction [transition]
Homo sapiens
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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
16385452 Epimerase-deficiency galactosemia is not a binary condition

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

Am. J. Hum. Genet. 2006
22613355 Altered cofactor binding affects stability and activity of human UDP-galactose 4'-epimerase: implications for type III galactosemia

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

Biochim. Biophys. Acta 2012
9973283 Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia

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

Am. J. Hum. Genet. 1999
Catalyst Activity

UDP-glucose 4-epimerase activity of GALE V94M:GALE V94M:NAD+:NAD+ [cytosol]

Normal reaction
Functional status

Loss of function of GALE V94M:GALE V94M:NAD+:NAD+ [cytosol]

Name Identifier Synonyms
galactosemia DOID:9870 Galactose intolerance, Galactosaemia
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