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140 ENERGY METABOLISM – TRYPANOSOMATIDAE
PART II: AEROBIC PROTISTS – TRYPANOSOMATIDAE
Fred R. Opperdoes and Paul A.M. Michels
Christian de Duve Institute of Cellular Pathology,
Catholic University of Louvain, Brussels, Belgium
INTRODUCTION
This chapter focuses on the carbohydrate
metabolism of the Trypanosomatidae, protozoan
parasites responsible for a number of
important diseases of man. Many enzymes of
glycolysis and related pathways in trypanosomatids
are sequestered inside microbodies,
which renders them interesting not only as a
drug target but also for basic research. The
potential for chemotherapeutic exploitation of
carbohydrate metabolism is significant. Questions
such as: which enzymes are the best to
target; what further information is required to
allow their use for rational drug development;
what compounds would constitute the best
inhibitors and which of the enzymes of the
hexose-monophosphate pathway are present
inside the glycosomes, are addressed (see also
Chapter 17).
The biochemistry of trypanosomes has
been studied in great detail, mainly owing to
the fact that these organisms harbor many
peculiarities which have attracted biochemists
interested in fundamental aspects of these
organisms. The fact that trypanosomes are
amongst the few parasitic organisms that can
easily be grown in large numbers in the blood
of infected rodents has facilitated their study.
The advent of molecular biology, where the
number of cells available for research is no
longer a limiting factor, has led to an enormous
growth of the literature over recent years. The
expected availability of the complete genome
sequence of Trypanosoma brucei is expected to
give a tremendous boost to our understanding
of trypanosome biology.
T. brucei is one of the best studied representatives
of the so-called African trypanosomes.
T.b. brucei, T.b. rhodesiense and T.b. gambiense
are responsible for nagana in cattle, and human
sleeping sickness in East and West Africa,
respectively. One of the most exciting areas of
research has been the remarkable organization
of the trypanosome’s carbohydrate metabolism,
where many enzymes of this pathway are
sequestered within a peroxisome-like organelle
called the glycosome. For a more detailed
description of the earlier work the reader is
referred to a number of older reviews (Further
Reading). The more recent information about
the bloodstream-form trypanosomes will be
discussed here, together with what is known
about the procyclic insect stage.
THE EMBDEN–MEYERHOF–
PARNAS (EMP) PATHWAY
OF GLYCOLYSIS
In the bloodstream-form trypanosome, glucose
serves essentially as the sole source of carbon
and energy, but fructose, mannose and glycerol
can be metabolized as well. This stage dwells in
the blood and tissue fluids of its mammalian
host, where it has access to an unlimited source
of glucose which is maintained relatively constant
at a concentration of 5 mM. Glucose is
metabolized by a form of aerobic fermentation
at a rate exceeding that found in most other
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA