trans

AMINO ACID METABOLISM 187
α-ketobutyrate
Threonine dehydratase
NH 3
THREONINE
Threonine dehydrogenase
2-amino-3-ketobutyrate
LIPIDS
Amino acetone synthase
GLYCINE Acetyl-CoA
Deacylase
OH 2
Acetate
FIGURE 8.4 Catabolic pathways for threonine.
PHENYLALANINE, TYROSINE, TRYPTOPHAN
TAT
Phenyl pyruvate, p-OH-phenyl pyruvate,
Indolyl pyruvate
NADH
AHADH
NAD
Phenyl lactate, p-OH-phenyl lactate,
Indolyl lactate
Pyruvate, oxaloacetate,
-ketoglutarate
alanine, aspartate,
glutamate
FIGURE 8.5 Catabolism of aromatic amino acids in
Trypanosoma cruzi. TAT, tyrosine aminotransferase;
AHADH, aromatic L--hydroxy acid dehydrogenase.
The pyridoxal 5-phosphate-dependent enzyme
threonine dehydratase, present in trichomonads,
Entamoeba and Giardia, dehydrates and
deaminates threonine yielding -ketobutyrate
and ammonia. In T. brucei, this enzyme is
absent and a different pathway is operative.
Threonine dehydrogenase produces 2-amino-
3-ketobutyrate, which is split into glycine
and acetyl-CoA in the reaction catalyzed by
aminoacetone synthase (acetyl-CoA:glycine
C-acetyl transferase). This acetyl-CoA is not
oxidized in the TCA cycle, but instead the
acetate moiety is incorporated into fatty
acids. The dehydrogenase is strongly inhibited
by tetraethylthiouram disulfide (disulfiram),
which also inhibits parasite growth.
As noted above, serine can be interconverted
with cysteine in some protozoan parasites.
Serine dehydratase has been detected in trophozoites
of E. histolytica. Serine and glycine can
also be interconverted in the serine hydroxymethyltransferase
reaction (see below).
Aromatic amino acids
The catabolism of aromatic amino acids in
T. brucei results in the excretion of the aromatic
lactate derivatives into the medium; indeed, in
animals with heavy parasitemias, some of these
catabolites can be detected in blood and urine.
Epimastigotes of T. cruzi also excrete into the
medium small amounts of phenyl lactate and
p-hydroxyphenyl lactate, as well as a derivative
of indolyl lactate. Tyrosine aminotransferase
(TAT) and aromatic L--hydroxy acid dehydrogenase
(AHADH) (Figure 8.5), have been characterized
from epimastigotes of T. cruzi.
The T. cruzi TAT has high homology with the
mammalian TAT, although, in contrast to the
mammalian enzyme, also exhibits substantial
alanine aminotransferase activity. AHADH,
the first enzyme described with this stereospecificity,
has high homology with cytosolic
malate dehydrogenases (cMDHs). T. cruzi has
two MDH activities, one mitochondrial and
the other glycosomal, and no evidence for
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA