Berry Gerard T, Reynolds Robert A, Yager Claire T, Segal Stanton
Department of Pediatrics, Division of Human Genetics and Molecular Biology and the Metabolic Research Laboratory, University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, PA 19104, USA.
Mol Genet Metab. 2004 Jun;82(2):130-6. doi: 10.1016/j.ymgme.2004.03.003.
Since patients with galactose-1-phosphate uridyltransferase (GALT) deficiency have considerable endogenous galactose formation and only limited urinary excretion of galactose metabolites, there must be mechanisms for disposal of the sugar. Otherwise, a steady-state could not be maintained and there would be continuous body accumulation of galactose and alternate pathway products. Previous studies quantitating the amount of galactose handled by oxidation to CO2 focused on short collection periods of expired air after administering isotopically labeled galactose mainly designed for discerning differences in the capacity to oxidize the sugar in relation to genotype. Assuming that there may be more extensive oxidation than that observed in short-term studies in order to dispose the daily galactose burden, we have examined the amount of [1-13C]galactose oxidized to 13CO2 over a 24-h period after either a single bolus or continuous IV administration by 11 patients with classic galactosemia including patients homozygous for the Q188R gene mutation. As much as 58% of the administered galactose was oxidized to 13CO2 in 24 h. The pathways involved remain to be determined but a significant amount may be metabolized by non-GALT pathways since a patient homozygous for gene deletion had an oxidative capability. We conclude that classic patients have the ability to slowly oxidize galactose to CO2 in 24 h in amounts comparable to that which a normal handles in approximately one-fifth the time. This capacity enables the galactosemic to maintain a balance of galactose disposal with the galactose burden imposed by endogenous formation and dietary intake.
由于1-磷酸半乳糖尿苷转移酶（GALT）缺乏症患者体内有相当数量的内源性半乳糖生成，而半乳糖代谢产物的尿排泄量有限，因此必然存在处理这种糖类的机制。否则，无法维持稳态，半乳糖及其替代途径产物会在体内持续蓄积。以往对通过氧化生成二氧化碳来处理的半乳糖量进行定量的研究，主要关注在给予同位素标记的半乳糖后短时间内收集呼出气体，其目的主要是辨别不同基因型在氧化该糖类能力上的差异。假设为了处理每日的半乳糖负荷，可能存在比短期研究中观察到的更广泛的氧化作用，我们检测了11例经典型半乳糖血症患者（包括Q188R基因突变纯合子患者）在单次推注或持续静脉输注[1-¹³C]半乳糖后24小时内氧化生成¹³CO₂的量。在24小时内，高达58%的输注半乳糖被氧化生成¹³CO₂。其中涉及的途径尚待确定，但由于一名基因缺失纯合子患者具有氧化能力，可能有相当数量的半乳糖通过非GALT途径代谢。我们得出结论，经典型半乳糖血症患者有能力在24小时内将半乳糖缓慢氧化为二氧化碳，其氧化量与正常人在大约五分之一的时间内处理的量相当。这种能力使半乳糖血症患者能够在内源性生成和饮食摄入所带来的半乳糖负荷与半乳糖处理之间维持平衡。
