The nature of cGMP transport in human erythrocytes, its
relationship to glutathione conjugate transport, and pos-sible mediation by multidrug resistance-associated proteins
(MRPs) have been investigated. MRP1, MRP4 and MRP5
are detected in immunoblotting studies with erythrocytes.
MRP1and MRP5 are also detected in multidrug resistant
COR-L23/R and MOR/R cells but at greatly reduced levels
in the parent, drug sensitive COR-L23/P cells. MRP4 is
detected in MOR/R but not COR-L23/R cells.
GlutathioneS-transferases (GSTs) catalyze the conjugation of glutathione
to hydrophobic compounds, contributing to the metabolism of toxic
chemicals. In this study, we show that two naturally occurring tau GSTs
(GSTUs) exhibit distinctive kinetic parameters towards 1-chloro-2,4-dini-trobenzene (CDNB), although they differ only in three amino acids
(Arg89, Glu117 and Ile172 in GSTU1 are replaced by Pro89, Lys117 and
Val172 in GSTU2).
What is ‘biochemical pharmacology’?
• A fancy way of saying ‘pharmacology’, and of hiding
the fact that we are sneaking a subject of medical interest
into the UW biochemistry curriculum.
• An indication that we are not going to discuss prescriptions
for your grandmother’s aching knee; we will focus
on the scientific side of things but not on whether to take
the small blue pill before or after the meal.
What is it not?
• A claim that we accurately understand the mechanism
of action of each practically useful drug in biochemical
The human multidrug resistance-associated protein (MRP1) is an ATP-dependent eﬄux pump that transports anionic conjugates, and hydrophobic compounds in a glutathione dependent manner. Similar to the other, well-characterized multidrug transporter P-gp, MRP1 comprises two nucleotide-binding domains (NBDs) in addition to transmembrane domains. However, whereas the NBDs of P-gp have been shown to be functionally equivalent, those of MRP1 diﬀer signiﬁcantly.
Glutathione (GSH) conjugating enzymes, glutathioneS-transferases (GSTs),
are present in different subcellular compartments including cytosol,
mitochondria, endoplasmic reticulum, nucleus and plasma membrane. The
regulation and function of GSTs have implications in cell growth, oxidative
stress as well as disease progression and prevention.
TheSaccharomyces cerevisiae vacuolar ATP-binding cassette transporter
Ycf1p is involved in heavy metal detoxification by mediating the ATP-dependent transport of glutathione–metal conjugates to the vacuole. In the
case of selenite toxicity, deletion of YCF1was shown to confer increased
resistance, rather than sensitivity