title: UDP-galactose pyrophosphorylase in mice with galactose-1-phosphate uridyltransferase deficiency.
abstract: UDP-glucose pyrophosphorylase (E.C. 2.7.7.9), encoded by ugp, provides UDP-glucose which is critical to the synthesis of glycogen, and also catalyzes the reaction between UTP and galactose-1-phosphate, yielding UDP-galactose. This activity of UDP-gal pyrophosphorylase (UDP-galPP) suggests a role in an alternate pathway for galactose metabolism in patients with deficiency of galactose-1-phosphate uridyltransferase (GALT). We examined the effects of GALT deficiency and dietary galactose on UDP-glucose pyrophosphorylase (UDP-gluPP) and UDP-galactose pyrophosphorylase activity and ugp expression in liver of mice with homozygous deletion of the critical regions of galt. Activity with glucose-1-phosphate as substrate was significantly higher than that with galactose-1-phosphate. In liver from mice with GALT deficiency (G/G), UDP-galPP activity appeared to be lower than that measured in liver from control (N/N) animals. This difference disappeared when the N/N tissue homogenate was dialyzed to remove residual UDP-glucose, confirming that careful elimination of residual GALT activity is necessary, since GALT has 1000-fold greater activity toward galactose-1-phosphate than that of UDP-galPP in liver homogenates. Prior exposure to conventional mouse chow, high galactose chow, and high glucose chow did not alter UDP-glu PP or UDP-galPP activity. Steady state UGP mRNA levels were determined in tissues from normal and G/G animals. UGP expression was highest in liver, and did not differ by genotype or exposure to high galactose chow. UDP-galPP activity may account for unexplained ability to oxidize galactose in animals with no GALT activity, but is insufficient to alter accumulation of galactose metabolites.
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA. nancy.leslie@cchmc.org
authors.forename: Nancy
authors.initials: N
authors.lastname: Leslie
authors.forename: Claire
authors.initials: C
authors.lastname: Yager
authors.forename: Robert
authors.initials: R
authors.lastname: Reynolds
authors.forename: Stanton
authors.initials: S
authors.lastname: Segal
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D005690:Galactose / Q000378:metabolism*; D005693:Galactosemias / Q000201:enzymology* / Q000235:genetics; D007700:Kinetics; D051379:Mice; D006599:UDPglucose-Hexose-1-Phosphate Uridylyltransferase / Q000172:deficiency*; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000378:metabolism*
chemical_list: D005694:UTP-Hexose-1-Phosphate Uridylyltransferase; D006599:UDPglucose-Hexose-1-Phosphate Uridylyltransferase; D005690:Galactose