Regulatory Metabolic Complex for Glucose Metabolism
in Living Cells: the Glucosome, Dr. Songon An; UMBC
Sequential metabolic enzymes of glucose
metabolism have long been hypothesized to form multienzyme complexes that
regulate glucose flux in living cells. However, it has been challenging to
directly observe these complexes and their functional roles in living systems.
Using quantitative live-cell imaging, we provide multiple lines of compelling
evidence that the cytosolic, rate-limiting enzymes in human glucose metabolism
are spatially organized into various sizes of cytosolic clusters in cells.
Subsequent biophysical characterizations further support the formation of
multienzyme metabolic complexes in cells. Importantly, high-content metabolic
flux assays reveal that the direction of glucose flux between glycolysis, the
pentose phosphate pathway and serine biosynthesis is spatially regulated by the
multienzyme complexes in a cluster size-dependent manner. Collectively, we demonstrate
a functionally active, multienzyme metabolic complex for glucose metabolism in
living human cells.