GLUCOSE-6-PHOSPHATE-DEHYDROGENASE - A HOUSEKEEPING ENZYME SUBJECT TO TISSUE-SPECIFIC REGULATION BY HORMONES, NUTRIENTS, AND OXIDANT STRESS

The enzyme, glucose-6-phosphate dehydrogenase (G6PDH, EC1.1.1.49), has long been considered and studied as the archetypical X-linked ''house keeping'' enzyme that is present in all cells, where it plays the key role in regulating carbon how through the pentose phosphate pathway. S pecifically, the enzyme catalyzes the first reaction in the pathway le ading to the production of pentose phosphates and reducing power in th e form of NADPH for reductive biosynthesis and maintenance of the redo x state of the cell. It was in this latter function that the crucial i mportance 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, ther e are several other tissues (liver, adipose, lung, and proliferating c ells) wherein modulation of cellular G6PDH activity represents an impo rtant component of the integrated response to external stimuli (hormon es, growth factors, nutrients, and oxidant stress). In this regard, ad aptive regulation of G6PDH has been found to be exerted at transcripti onal 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 sin gle 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.