SUGAR NUCLEOTIDE CONCENTRATIONS IN RED-BLOOD-CELLS OF PATIENTS ON PROTEIN-LIMITED AND LACTOSE-LIMITED DIETS - EFFECT OF GALACTOSE SUPPLEMENTATION

Uridine diphosphate (UDP) galactose, a pivotal compound in the metabol ism of galactose, is the obligate donor of galactose in the formation of complex glycoconjugates. The cellular UDP galactose concentration h as been thought to be maintained by the interconversion of UDP glucose and UDPgalactose by UDPgalactose-4-epimerase. However, recent finding s of lower average red blood cell (RBC) UDPgalactose concentrations in galactose-1-phosphate uridyltransferase-deficient patients suggest th at other factors play a role in determining its concentration. To test the hypothesis that the amount of galactose traversing the Leloir pat hway contributes to the cellular UDPgalactose pool, we determined RBC UDPgalactose in patients with maple syrup urine disease (MSUD), phenyl ketonuria (PKU), and other metabolic diseases who were treated with a low-protein, and consequently, low-lactose diet. Six patients with MSU D were also supplemented with 19 g galactose/d and their UDPhexose con centrations were measured at intervals. We show that young patients wi th MSUD or PKU have decreased average RBC UDPgalactose concentrations when compared with similarly aged healthy subjects. Galactose suppleme ntation of MSUD patients significantly increased their UDPgalactose co ncentrations in both RBCs and white blood cells (WBCs) from 29.5 +/- 1 .5 to 42.3 +/- 5.8 nmol/g hemoglobin and from 69.0 +/- 7.5 to 193.0 +/ - 49.0 nmol/g protein, respectively. Discontinuation of supplementatio n was associated with a return to basal values in RBCs and a reattainm ent of the pretreatrnent ratio of UDPglucose to UDPgalactose in WBCs. These observations demonstrate that dietary galactose is a factor in e stablishing the steady state concentrations of the uridine sugar nucle otides and imply that galactose metabolism modulates the achievement o f an epimerase-mediated equilibrium.