trans

AMINO ACID METABOLISM 183
appears to be a circulating antigen in infected
humans, and may become useful for the
immunodiagnosis of malaria.
Aminotransferases and glutamate dehydrogenases
also have been described in many
helminths. Although many different substrate
specificities have been detected for aminotransferases,
most of the enzymes have not
yet been characterized. Alanine and aspartate
aminotransferase activities seem to be predominant,
as in protozoa. Ammonia, a product
of the glutamate dehydrogenase reaction,
is usually excreted directly into the medium.
Urea is excreted by a number of parasites;
however, it apparently arises from arginine
catabolism and not from the functioning of
the urea cycle, which has never been properly
demonstrated in any parasite.
Amino acid catabolism
Proline
This amino acid is an important source of
energy for some protozoa, particularly those
stages of hemoflagellates present in the insect
vector, where these parasites must live on
the products of protein digestion in the gut.
In addition, proline is a major energy source
for insects, and is present in large quantities
in the hemolymph. Proline catabolism leads
to the formation of glutamate, which, by
transamination, is able to enter the TCA cycle
as -ketoglutarate (Figure 8.2). Since the cycle
is frequently incomplete, or the respiratory
chain is not able to cope with the reducing
equivalents generated by catabolism, succinate,
alanine and aspartate often accumulate
as the final products of proline catabolism.
In T. brucei, bloodstream forms are incapable
of metabolizing proline, in contrast to insect
forms of the parasite. Although proline oxidase
has not been directly demonstrated in
Plasmodium spp., plasmodial mitochondria
are able to oxidize proline.
Proline metabolism has been studied in less
detail in helminths. All the enzymes of proline
catabolism have been detected in the nematodes
Heligmosomoides polygyrus and Panagrellus
redivivus, with activities similar to those
present in rat liver. Proline decarboxylation
has been detected in Ancylostoma ceylanicum
and Nippostrongylus brasiliensis. Proline oxidation
appears to be stage-dependent. Cell-free
extracts of Brugia pahangi microfilariae are
much more active in proline oxidation, measured
as 14 CO 2 formation, than are homogenates
of the adults. Some helminths contain
significant amounts of hydroxyproline, formed
by the post-translational modification of proline.
In F. hepatica, hydroxyproline is found
in a number of soluble proteins, including a
cysteine proteinase. In Onchocerca volvulus
hydroxyproline is found in the adult cuticle,
but is absent in eggs and nodular microfilariae,
suggesting that extensive proline hydroxylation
accompanies cuticular maturation of the
parasite in the human host.
Arginine
The three major pathways for arginine catabolism
are illustrated in Figure 8.2. In most parasites,
as well as in higher animals, arginine is
catabolized through the concerted action of
arginase and ornithine aminotransferase yielding
glutamate semialdehyde, which is then
converted to glutamate. Ornithine can be used
for polyamine biosynthesis (see below). The
-guanidinobutyramide pathway in L. donovani
leads to the formation of succinate which
enters the TCA cycle. Arginine decarboxyoxidase
uses O 2 in the presence of Mg 2 , Mn 2 ,
FMN and pyridoxal phosphate, to produce
CO 2 and -guanidinobutyramide. The arginine
dihydrolase pathway, present in G. lamblia,
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA