trans

190 PROTEIN METABOLISM
Urea
ARGININE
(1)
Ornithine
(3)
CO CO 2 2
Urea
(2)
(10)
Agmatine
(4)
Putrescine
(12)
SAM
Dec-SAM
(5)
N-acetyl spermidine
ATP
(9)
5-MTA
(11)
METHIONINE
MR
(7)
ATP
Spermidine
(6)
(12)
N-acetyl spermine
Glutathionyl spermidine
GSH
GSH
(8)
Spermine
(11)
ATP
TRYPANOTHIONE
FIGURE 8.7 Role of methionine and arginine in polyamine biosynthesis. SAM, S-adenosylmethionine; Dec-SAM,
decarboxylated S-adenosylmethionine; MR, methionine recycling (Figure 8.3); GSH, reduced glutathione.
(1) arginase; (2) ornithine decarboxylase; (3) arginine decarboxylase; (4) agmatine deiminase; (5) spermidine
synthase; (6) spermine synthase; (7) glutathionylspermidine synthetase; (8) trypanothione synthetase;
(9) S-adenosylmethionine synthetase; (10) S-adenosylmethionine decarboxylase; (11) polyamine acetylase;
(12) diamine oxidase.
for the metabolic instability of mammalian
ODC. However, the C. fasciculata ODC, which
has a short half-life, also lacks this sequence,
so that there is clearly more to this story.
The crystal structure of a recombinant ODC
from T. brucei indicates that the active site is
identical to that of the mammalian enzyme.
L. donovani ODC deletion mutants behave as
polyamine auxotrophs. An alternative to ODC
is arginine decarboxylase, which decarboxylates
arginine to agmatine, which is then converted
to putrescine by agmatine deiminase.
This enzyme has been recently described in
Cryptosporidium parvum. Although arginine
decarboxylase activity has been reported in
T. cruzi, this is still controversial, and the parasite
usually behaves as a polyamine auxotroph.
The second enzyme in the biosynthetic
pathway, spermidine synthase (Figure 8.7)
transfers the aminopropyl group from decarboxylated
S-adenosyl methionine (decSAM)
to putrescine to yield spermidine. Although
P. falciparum contains spermine, it is probably
taken up from the medium.
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA