Recent Advances in Hepatic Glucose 6-Phosphatase Regulation and Function

Areas which we believe merit immediate intensive study include (i) isolation and characterization, chemically and functionally, of all of the individual components of the system; (ii) characterization of possible multiple forms of transport components, as we have done with T2 (24, 25, 36); (iii) optimistically, the reassembly of these components into a functional unit within synthetic biomembranes; (iv) characterization of the impact of components of biomembranes upon function of the various components; (v) cloning of all of the individual proteins of the system; (vi) characterization of mechanisms regulating the biosynthesis of the individual proteins at the transcriptional and translational levels; (vii) demonstration of possible auxiliary functions of translocases other than exclusively with the glucose 6-phosphatase system; (viii) characterization of possible physical associations of some components of the system; (ix) characterization of the glucose 6-phosphatase system from nonhepatic sources; (x) characterization of physiologic roles of the glucose 6-phosphatase system, and possibly its individual components, in nonhepatic tissues; (xi) elucidation of the physiologic significance of differential rates of appearance of individual components of the system during development; (xii) further determination of the physiologic significance of the multiple activities (hydrolytic and biosynthetic) of the glucose 6-phosphatase system; and (xiii) identification of additional factors—metabolite inhibitions, co-valent modifications through protein phosphorylation/dephosphorylation and the like—which may regulate both hydrolytic and biosynthetic functions in discriminant, short-term fashion. Future studies of this least understood and most complex of gluconeogenic enzymes seem to us poised at the edge of a golden era. We have been a part of the events leading to that positioning, and hope to be a part of future exciting developments as well. The work from authors' laboratory described above was supported in part by Research Grant DK07141 from the National Institutes of Health, U.S. Public Health Service, and by the Dakota and Minnesota Aeries of Eagles.