<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto"
id="d114197e86">Metabolic diseases, including obesity, type 2 diabetes, and metabolic
syndrome arise
because of disturbances in glucose and fat metabolism, which impact associated physiological
events such as insulin secretion and action, fat storage and oxidation. Even though,
decades of research has contributed to our current understanding of the components
involved in glucose and fat metabolism and their regulation, that led to the development
of many therapeutics, there are still many unanswered questions. Glycerol-3-phosphate
(Gro3P), which is formed during glycolysis, is at the intersection of glucose and
fat metabolism, and the availability of this metabolite can regulate energy and intermediary
metabolism in mammalian cells. During the course of evolution, mammalian cells are
assumed to have lost the capacity to directly hydrolyze Gro3P to glycerol, until the
recent discovery from our laboratory showing that a previously known mammalian enzyme,
phosphoglycolate phosphatase (PGP), can function as a Gro3P phosphatase (G3PP) and
regulate this metabolite levels. Emerging evidence indicates that G3PP/PGP is an evolutionarily
conserved "multi-tasking" enzyme that belongs to the superfamily of haloacid dehalogenase-like
phosphatase enzymes, and is capable of hydrolyzing Gro3P, an abundant physiologically
relevant substrate, as well as other metabolites including 2-phosphoglycolate, 4-phosphoerythronate
and 2-phospholactate, which are present in much smaller amounts in cells, under normal
conditions. G3PP, by regulating Gro3P levels, plays a critical role in intermediary
metabolism, including glycolysis, glucose oxidation, cellular redox and ATP production,
gluconeogenesis, esterification of fatty acids towards glycerolipid synthesis and
fatty acid oxidation. Because of G3PP's ability to regulate energy and intermediary
metabolism as well as physiological functions such as insulin secretion, hepatic glucose
production, and fat synthesis, storage and oxidation, the pathophysiological role
of this enzyme in metabolic diseases needs to be precisely defined. In this review,
we summarize the present knowledge on the structure, function and regulation of G3PP/PGP,
and we discuss its potential therapeutic role for cardiometabolic diseases.
</p>