O -P -O —P -O — P-O-CH
o —S -O — P-O-CH
Adenosine 5 -phosphosulfate (APS)
5 -Phosphoadenosine 3 -phosphosulfate (PAPS)
P A P S
P A P
Figure 40-2. Formation of 5'-phosphoadenosine 3'-phosphosulfate (PAPS)
and sulfated acetaminophen.
two phases. The first phase consists of preparing activated sulfate for transfer
as 5'-phosphoadenosine 3'-phosphosulfate (PAPS), and the second consists
of transfer of the sulfate moiety to acetaminophen. In the first step of the
first phase, ATP-sulfurylase catalyzes the formation of pyrophosphate and
adenosine-5'-phosphosulfate (APS) from ATP and sulfate. In the second step,
APS-kinase catalyzes the formation of PAPS and adenosine diphosphate
(ADP) from ATP and APS. (The structure for PAPS is shown in Figure 40-2.)
In the second phase, phenolsulfotransferase, one of a group of sulfotrans-
ferases, transfers the sulfate group from PAPS to acetaminophen to yield
adenosine-3',5'-bisphosphate and acetaminophen sulfate, which is eliminated.
In the event that this pathway and the glucuronide forming pathway are both
overwhelmed by overdose, more acetaminophen is metabolized by the
cytochrome P450 pathway.
Oxidative metabolism of acetaminophen by the cytochrome P450 system,
shown in Figure 40-3, is catalyzed by various cytochromes P450 such as
quinoneimine, an unstable intermediate shown in Figure 40-3, which can