Biology Reference
In-Depth Information
Fig. 13.1 The three possible irreversible precursor-product relationships between two precursors
(
P
,
A
) and one end product (
B
) (Adapted from Rebeiz et al.
1988
)
where:
QB
2
¼
amount of radiolabel incorporated into compoundB during time interval t
1
-t
2
;
*A
1
,*A
2
¼
specific radioactivity of compound A at the beginning and end of time
interval t
1
-t
2
respectively.
*B
2
¼
amount of compound B synthesized during time interval t
1
-t
2
.
By comparing expected radiolabel incorporation into compound B, as calculated
from Eq.
13.1
, with experimentally determined incorporations into compound B,it
is possible to tell whether compound B was formed exclusively from compound
A or not. If compound B is formed exclusively from compound A, then within
the range of experimental error, the theoretical and experimental radiolabel incor-
porations into compound B should be identical or reasonably similar. On the other
hand, if compound B is not formed from compound A, or is partially formed from
compound A, then the calculated and experimental radiolabel incorporations into
compound B will be different. The difference between the calculated and experi-
mental values may then depend, among other things, on the extent of partial
contribution of compound A to the synthesis of compound B.
If comparison of calculated and experimental results indicates that compound
B is not totally formed from compound A via pathway 1 (Fig.
13.1
), then the
question arises as to whether compound B is formed via pathway 2 or 3. Further-
more if compound B is found to be formed via pathway 2, then the contribution of
compound A to the formation of compound B needs to be assessed. The determina-
tion of whether compound B is formed via pathway 2 or 3 can be achieved from
conventional in vitro investigations of precursor product relationship between
compound A and compound B. In other words, if pathway 2 is found to be opera-
tional then the contribution of compound A to the formation of compound B can be
assessed from Eq.
13.2
(Rebeiz et al.
1988
):
Conversion
¼
100
½
ð
j
Exp
QB
X
j
=
Exp
Þ
100
(13.2)
%
where:
% Conversion
maximum possible percent conversion of compound A to com-
pound B during any time interval X,
Exp
¼
actual
14
C-incorporation into compound B by the end of time interval X, as
determined experimentally,
¼
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