Variability of glutathione S-transferase alpha in human liver and plasma

BACKGROUND: Glutathione S-transferases are a family of enzymes involved in the binding, transport, and detoxification of a wide variety of endogenous and exogenous compounds. Little information is available about the variability of class alpha glutathione S-transferases in human liver, where they are highly expressed, or in serum. METHODS: Both total class alpha glutathione S-transferase (GST-alpha, composed of GSTA1-1, GSTA1-2, and GSTA2-2) as well as GSTA1-1 concentrations were measured by specific and sensitive ELISA in liver cytosols of 35 organ donors and in plasma samples of 350 healthy controls. RESULTS: The mean total GST-alpha and GSTA1-1 in liver cytosols were 25.1 +/- 9.4 and 10.7 +/- 5.3 microg/mg protein, respectively, and did not correlate with activities of aspartate aminotransferase or alanine aminotransferase. The mean total GST-alpha in liver was significantly higher in females compared with males (28.8 +/- 10.0 vs 22.0 +/- 7.8 microg/mg protein; P <0.05). In contrast, the median total GST-alpha in plasma was lower in females compared with males (2.0 and 2.8 microg/L, respectively; P <0.0001). The median ratios for GSTA1-1/total GST-alpha in liver and plasma were 0.42 and 0.58, respectively. CONCLUSIONS: GSTA1-1 constitutes approximately one-half of the total amount of alpha class GSTs in human plasma and liver. Total GST-alpha values are higher in female liver but lower in plasma compared with the respective values in males.