Gibson J B, Berry G T, Palmieri M J, Reynolds R A, Mazur A T, Segal S
Division of Biochemical Development, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 19104, USA.
Am J Clin Nutr. 1996 May;63(5):704-8. doi: 10.1093/ajcn/63.5.704.
Uridine diphosphate (UDP) galactose, a pivotal compound in the metabolism of galactose, is the obligate donor of galactose in the formation of complex glycoconjugates. The cellular UDPgalactose concentration has been thought to be maintained by the interconversion of UDPglucose and UDPgalactose by UDPgalactose-4-epimerase. However, recent findings of lower average red blood cell (RBC) UDPgalactose concentrations in galactose-1-phosphate uridyltransferase-deficient patients suggest that other factors play a role in determining its concentration. To test the hypothesis that the amount of galactose traversing the Leloir pathway contributes to the cellular UDPgalactose pool, we determined RBC UDPgalactose in patients with maple syrup urine disease (MSUD), phenylketonuria (PKU), and other metabolic diseases who were treated with a low-protein, and consequently, low-lactose diet. Six patients with MSUD were also supplemented with 19 g galactose/d and their UDPhexose concentrations were measured at intervals. We show that young patients with MSUD or PKU have decreased average RBC UDPgalactose concentrations when compared with similarly aged healthy subjects. Galactose supplementation of MSUD patients significantly increased their UDPgalactose concentrations 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 supplementation was associated with a return to basal values in RBCs and a reattainment of the pretreatment ratio of UDPglucose to UDPgalactose in WBCs. These observations demonstrate that dietary galactose is a factor in establishing the steady state concentrations of the uridine sugar nucleotides and imply that galactose metabolism modulates the achievement of an epimerase-mediated equilibrium.
尿苷二磷酸（UDP）半乳糖是半乳糖代谢中的关键化合物，是复杂糖缀合物形成过程中半乳糖的专一性供体。细胞内UDP半乳糖浓度一直被认为是通过UDP半乳糖-4-表异构酶催化UDP葡萄糖和UDP半乳糖的相互转化来维持的。然而，最近在1-磷酸半乳糖尿苷酰转移酶缺乏症患者中发现平均红细胞（RBC）UDP半乳糖浓度较低，这表明其他因素在决定其浓度方面也发挥作用。为了验证穿过Leloir途径的半乳糖量有助于细胞UDP半乳糖池的这一假说，我们测定了枫糖尿症（MSUD）、苯丙酮尿症（PKU）和其他接受低蛋白（因此低乳糖）饮食治疗的代谢性疾病患者的红细胞UDP半乳糖水平。6例MSUD患者还每日补充19 g半乳糖，并定期测量其UDP己糖浓度。我们发现，与年龄相仿的健康受试者相比，患有MSUD或PKU的年轻患者平均红细胞UDP半乳糖浓度降低。给MSUD患者补充半乳糖后，其红细胞和白细胞（WBC）中的UDP半乳糖浓度显著增加，分别从29.5±1.5增至42.3±5.8 nmol/g血红蛋白，以及从69.0±7.5增至193.0±49.0 nmol/g蛋白质。停止补充后，红细胞中的浓度恢复到基础值，白细胞中UDP葡萄糖与UDP半乳糖的比例恢复到治疗前水平。这些观察结果表明，饮食中的半乳糖是建立尿苷糖核苷酸稳态浓度的一个因素，并意味着半乳糖代谢调节着表异构酶介导的平衡的实现。
