Study Set Content:
These microsomal enzymes catalyze the(balnk) of an
activated endogenous substance (such as the UDP
derivative of glucuronic acid) with a drug (or endogenous
compound such as bilirubin, the end product of heme
metabolism).
coupling
how many UGT genes (UGTA1 and UGT2) encode UGT
proteins involved in the metabolism of drugs and xenobiotics.
19
how many human sulfotransferases (SULTs) catalyze the sulfation
of substrates using 3′-phosphoadenosine 5 -phosphosulfate
(PAPS) as the endogenous sulfate donor.
11
are also engaged in the metabolism of drugs and
xenobiotics, and in that of leukotrienes and prostaglandins,
respectively.
Cytosolic and microsomal glutathione (GSH) transferases
(GSTs)
Chemicals containing an aromatic amine or a hydrazine moiety
(eg, isoniazid) are substrates of
cytosolic N-
acetyltransferases (NATs),
Chemicals containing an aromatic amine or a hydrazine moiety
(eg, isoniazid) are substrates of cytosolic N-
acetyltransferases (NATs), encoded by
NAT1 and NAT2
genes,
Chemicals containing an aromatic amine or a hydrazine moiety
(eg, isoniazid) are substrates of cytosolic N-
acetyltransferases (NATs), encoded by NAT1 and NAT2
genes, which utilize
acetyl-COA.
S-Adenosyl-L-methionine (SAMe; AdoMet)-mediated O-
,N-, and S-methylation of drugs and xenobiotics by
methyltransferases (MTs)
PHASE II Reactions:
GLUCORONIDATION (most common)
SULFATION (less common)
AMINO ACID CONJUGATION
METHYLATION
GLUTATHIONE CONJUGATION
ACETYLATION
GLUCORONIDATION (most common)
Alcohols, phenols, Carboxylic acids
uses UDPG-A as the
co-factor to transfer glucuronic acid to several
functional groups.
Glucuronosyltransferase
– Increases the polarity of
the parent drug by conjugation an endogenous molecule
to the xenobiotics.
SULFATION (less common)
SULFATION (less common)
Phenols, alcohols, amines
uses the co-factor 3′-
phosphoadenosine 5′-phosphosulfate (PAPS) to
add a sulfate, hydroxyl and aryl amine groups.
Sulfotransferase
adds either glycine or
glutamine to carboxylic acid
AMINO ACID CONJUGATION
AMINO ACID CONJUGATION
carboxylic acids
catalyzes the reaction of the
activated xenobiotic to form amide containing
metabolite.
N-acyltransferase
addition of methyl group to a O,N,S
groups
METHYLATION
METHYLATION
Phenol,thiol,amino groups,
N- containing heterocycles
METHYLATION transferase
Methyl-transferase
