4 DISTINCT MEMBRANE-BOUND DIPEPTIDASE RNAS ARE DIFFERENTIALLY EXPRESSED AND SHOW DISCORDANT REGULATION WITH GAMMA-GLUTAMYL-TRANSPEPTIDASE

Membrane-bound dipeptidase (MBD) participates in the degradation of gl utathione by cleaving the cysteinylglycine bond of cystinyl bisglycine (oxidized cysteinylglycine) following removal of a gamma-glutamyl gro up by gamma-glutamyl transpeptidase (GGT). In the mouse, MBD RNA is mo st abundant in small intestine, kidney, and lung and is represented by four distinct RNA species, These are generated by transcription from two promoters located 6 kilobases apart in the 5' flanking region of t he gene and by the use of two different poly(A) addition sites, Promot er I is used primarily in small intestine and kidney, whereas promoter II is most active in lung and kidney, We found a discordance in the e xpected co-expression of MBD and GGT; as expected, MBD and GGT are bot h expressed at high levels in the kidney and small intestine, However, in the lung, MBD is expressed at high levels, whereas GGT is almost u ndetectable, The reverse is true in the seminal vesicles and fetal liv er. Thus, although both enzymes may function in concert to metabolize glutathione in kidney and small intestine, in other tissues they appea r to act independently, suggesting that they have independent roles in other biological processes.