Kletzien R F, Harris P K, Foellmi L A
Upjohn Laboratories, Upjohn Company, Kalamazoo, Michigan 49001.
FASEB J. 1994 Feb;8(2):174-81. doi: 10.1096/fasebj.8.2.8119488.
The enzyme, glucose-6-phosphate dehydrogenase (G6PDH, EC1.1.1.49), has long been considered and studied as the archetypical X-linked "housekeeping" enzyme that is present in all cells, where it plays the key role in regulating carbon flow through the pentose phosphate pathway. Specifically, the enzyme catalyzes the first reaction in the pathway leading to the production of pentose phosphates and reducing power in the form of NADPH for reductive biosynthesis and maintenance of the redox state of the cell. It was in this latter function that the crucial importance of the enzyme was first appreciated with the description of the human deficiency syndrome. While the gene can be considered to be a constitutively expressed "housekeeping" gene in many tissues, there are several other tissues (liver, adipose, lung, and proliferating cells) wherein modulation of cellular G6PDH activity represents an important component of the integrated response to external stimuli (hormones, growth factors, nutrients, and oxidant stress). In this regard, adaptive regulation of G6PDH has been found to be exerted at transcriptional and posttranscriptional levels. However, the regulation observed is tissue-specific, which elicits the central question of this review, "How can the G6PDH gene be constitutively expressed in some tissues while displaying adaptive regulation in others when there exists a single transcription unit for the gene?" Future studies utilizing cloned genomic fragments of the human and other mammalian G6PDH genes should provide answers to this question.
葡萄糖-6-磷酸脱氢酶（G6PDH，EC1.1.1.49）长期以来一直被视为并研究为典型的X连锁“管家”酶，存在于所有细胞中，在调节通过磷酸戊糖途径的碳流中起关键作用。具体而言，该酶催化该途径中的第一个反应，导致产生戊糖磷酸和以NADPH形式存在的还原力，用于还原生物合成和维持细胞的氧化还原状态。正是在这后一种功能中，随着人类缺乏综合征的描述，人们首次认识到该酶的至关重要性。虽然该基因在许多组织中可被视为组成型表达的“管家”基因，但还有其他几种组织（肝脏、脂肪、肺和增殖细胞），其中细胞G6PDH活性的调节是对外部刺激（激素、生长因子、营养物质和氧化应激）综合反应的重要组成部分。在这方面，已发现G6PDH的适应性调节在转录和转录后水平发挥作用。然而，观察到的调节是组织特异性的，这引发了本综述的核心问题，“当该基因存在单个转录单元时，G6PDH基因如何在某些组织中组成型表达而在其他组织中表现出适应性调节？”利用人类和其他哺乳动物G6PDH基因的克隆基因组片段进行的未来研究应该能回答这个问题。
