IN VITRO REGULATION OF RAT LIVER GLYOXALASE II ACTIVITY BY NUCLEOTIDES

The glyoxalase system comprises two enzymes, namely glyoxalase I (E.C 4.4.1.5) and glyoxalase II (E.C 3.1.2.6). Glyoxalase II (Glo II) catalyzes the hydrolysis of S-D-Lactoylglutathione (SLG) to D-Lactate and Glutathione. This is the rate-limiting step in the conversion of methylglyoxal to D-Lactate. In addition to its role in the detoxification of cytotoxic 2-oxo-aldehydes, specifically methlyglyoxal, it has been suggested that the glyoxalase enzyme system may also play a role in controlling cell differentiation and proliferation. The purpose of this study was to determine whether or not a relationship exists between some nucleotides and in vivo modulation of Glo II. This study demonstrated that some nucleotides, such as Guanosine and Adenosine triphosphates, inhibit Glo II activity in vitro. We observed a non-competitive inhibition (=49%) of Glo II in crude preparation of rat liver by GTP (0.3 mM). A GTP analogue, 5′-guanylylimido diphosphate (GppNHp), showed similar inhibition to that of GTP, thereby suggesting the absence of involvement of GTPase activity. These inhibitions of Glo II by nucleotides suggest a mechanism whereby SLG levels can be modulated in vivo.