L3 (SULTs) Flashcards
True or false?
Sulfonylation of Drugs by SULT Enzymes
Cytosolic SULTs catalyze the transfer of the sulfonyl group of 3′-
phosphoadenosine 5′-phosphosulfate (PAPS) to hydroxyl, sulfhydryl,
amino, or N-oxide substituents in suitable endobiotics and xenobiotics
and generates sulfate conjugates that are readily excreted in urine.
True ✅
True or false ?
Sulfonation is a lower-capacity pathway than glucuronidation. Thus, many
drugs and other xenobiotics are substrates for both SULTs and UGTs, but
UGT-dependent pathways usually predominate.
True ✅
Complete :
There are two broad classes of SULTs:
1/ the membrane-bound SULTs that are
located in the Golgi apparatus and that mediate the sulfonation of proteins,lipids, and glycosaminoglycans
2/the cytosolic SULTs that mediate the sulfonation of drugs, other xenobiotics, and endogenous substrates include
steroids, bile acids.
Compete:
Three gene families of SULT Enzymes have been identified in humans:
1/SULT1 (located on
chromosome 16),
2/SULT2 (chromosome 19),
3/ SULT4 (chromosome 22).
True or false ?
SULT1A1 is the major SULT1A expressed in adult liver and
has also been detected in numerous extra-hepatic tissues.
True ✅
True or false ?
SULT1A3 is highly expressed in extra-hepatic tissues but only at
low level in liver.
True ✅
True or false?
SULT1A1 is active toward the substrates p-nitrophenol and minoxidil. SULT1A3 also sulfonates catecholamines such as dopamine. Together SULT1A1 and SULT1A3 are responsible for the metabolism of
most phenols, but the related SULT1A2 is less active in the sulfonation of
such substrates.
True ✅
True or false ?
SULT1A1 catalyzes the sulfonylation of 4-hydroxytamoxifen, to an important
active metabolite of the tamoxifen that is used in the treatment of breast
cancer patients.
True ✅
True or false ?
Arg213H is substitution in SULT1A1*2 alters activity, possibly by altering the
stability of the enzyme.
True ✅
True or false ?
A strong association between improving survival and the presence of the
SULT1A1*1 allele has been described in breast cancer patients who
received tamoxifen.
True ✅
True or false ?
Although not completely understood, sulfonylated 4-hydroxytamoxifen
potently activated programmed cell death in breast tumor cell lines.
True ✅
True or false ?
The rapid sulfonylation of active tamoxifen metabolites could stimulate tumor
cell apoptosis and improve survival in individuals with the high-activity wild-
type SULT1A1 alleles.
Conversely, individuals who are less competent in tamoxifen sulfonylation
may also be less responsive to the drug because formation of the pro-
apoptotic metabolite is diminished.
True ✅
