Background/aims:
GAPD has been exhaustively investigated as a key cytosolic
enzyme in glycolysis. In recent years
GAPD has also been implicated in many cellular activities unrelated to glycolysis. However, although various functions have been ascribed to
GAPD from rabbit muscle, human blood and rat tissues, no information is available on human liver
GAPD. We have recently demonstrated that, as a cellular
kinase,
GAPD might interfere in the life-cycle of hepatitis B virus. We therefore investigated the enzymatic activities and subcellular localization of
GAPD in normal human liver. Methods:
GAPD and hepatocyte membranes were isolated from human liver homogenates to study the subcellular localization and enzymatic activities of GADP (
kinase and
ADP-ribosyltransferase). Results: (i)
GAPD was recovered from the plasma-membrane-enriched fraction, in internal membranes, and in the cytosol; (ii)
GAPD could be phosphorylated, a phenomenon inhibited by both GAP and
NADH; and (iii)
GAPD exhibits
ADP-ribosyltransferase activity, which is stimulated by
nitric oxide in a concentration-dependent manner. Conclusions: Human liver
GAPD may play significant
biological roles in addition to glycolysis, especially in signal transduction and in intracellular processes possibly involved in HBV
infection.