schisto discussion reply

A.G.M. Tielens tielens at biochem.dgk.ruu.nl
Tue Jun 18 06:07:23 EST 1996


Dear colleagues,

I think the initiative of Patrick Skelly and Chuck Shoemaker to start
scientific Schistonet dialogues on selected aspects of schistosome research
is good and could be very stimulating.  I will gladly add some comments and
additional discussion topics.

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Regarding Issue 1-A:
Do females need males to obtain much of their glucose?

I don't think there is enough evidence to state that males transfer glucose
to females. Our experiments on paired and unpaired worms showed that females
do not need males for the synthesis of glycogen [Tielens et al. Pararasitol.
98 (1889) 67-73]. Unpaired females were well able to consume glucose without
the assistance of males, and unpaired females synthesized glycogen at the
same rate as paired females. Apparently the capacity for glucose uptake of
unpaired females is not only sufficient for the amount required for
immediate use, it is even large enough for the replenishment of depleted
glycogen stores. Our results do not exclude the possibility that, in vivo,
males stimulate the intake of host erythrocytes by the female [Gupta and
Basch, J.Par. 73(1987) 481]. However, an essential role of the male in the
uptake of glucose by the female is very unlikely now it is known that female
S. mansoni worms do not require any help for the uptake of glucose.



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Regarding issue 2:
What happens to the host glucose after absorption from the host?
What is the function of glycogen in adult schistosomes?

Relatively large glycogen stores are present in all stages of schistosomes.
The function of glycogen in free-living stadia is obvious as they have no
access to external food resources, and glycogen is their indispensible
energy reserve for the time they need to reach and penetrate a new host.
However, adult schistosomes also have large glycogen reserves throughout
their body, and these are metabolically active. We showed that these stores
are continuously replenished in vivo [MBP 39(1990)195-202]. Energy reserves
seem not necessary as these adult worms are surrounded by blood of the host
which provides a continuous supply of glucose. We suggested that glycogen is
used intermittently, for instance, for the muscle contractions necessary for
crawling, and that the glycogen stores are then (almost) instantaneously
replenished. Are there any other reasonable alternatives?

Additional question:
If these glycogen reserves are to be used in other cells than the ones the
glycogen is stored in, the gluconeogenic enzyme glucose 6-phosphatase will
have to be present in S. mansoni. We showed that this enzyme is indeed
present in adult schistosomes [Tielens et al., Parasitol. 102 (1991)
267-276]. In that same article we demonstrated that the other gluconeogenic
enzymes (Pyruvate carboxylase, FBPase and PEPCK) are also present in adult
schistosomes.
What can be the function of these enzymes in adult schistosomes?
Gluconeogenesis could not be demonstrated in that and other studies and,
indeed, it is difficult to conceive of this process in adults, as they never
encounter circumstances in which glucose is scarce or absent, and in which
at the same time gluconeogenic substrates are available. As long as the host
is alive, its glucostatic mechanisms will provide ample glucose for the
parasite in the bloodstream. However, no other function, for example
catabolic, could be assigned for the observed gluconeogenic enzymes. So, why
are they present? What is their function?


Maybe PEPCK, which is remarkably active in schistosomes, has a catabolic
function also in this parasite?
In other parasitic helminths PEPCK is known to be a catabolic enzyme,
necessary for malate dismutation. Adult schistosomes are known, however, to
degrade glucose mainly to lactate, but to rely also on Krebs cycle activity
for energy generation. Malate dismutation had never been demonstrated in
schistosomes. Recently, however, we showed that the sporocysts (in this case
in vitro transformed miracidia) produce a large amount of succinate via
PEPCK under anaerobic conditions [Tielens et al. MBP (1992) 49-58] This
succinate production does not occur in the preceding stage, the miracidia,
nor in cercariae or adults. Or does it occur and is the succinate further
metabolized or used for anabolic functions?, which would explain the
presence of the large PEPCK activity in adults that I mentioned above.

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Regarding issue 3
How does it benefit schistosomes to shut down oxidative metabolism upon
cercarial transformation?

I have discussed this matter in earlier publications [MBP 51(1992) 73-80,
Parasitol Today 10 (1994) 346-352].
I want to suggest that schistosomes switch for economic reasons to rapid
lactate production as soon as external glucose becomes available. Several
systems are known with a comparable rapid glycolytic flux. Hexokinase could
play a distinct role in this proces and we have recently shown that the
schistosomal hexokinase indeed has the required properties: a high affinity
for glucose and a moderate sensitivity to inhibition by glucose 6-phosphate
[Tielens et al. JBC 269(1994) 24736-24741].
See the 3 above mentioned papers for a more elaborate discussion on this topic.

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All the questions raised by Skelly and Shoemaker clearly demonstrate that
the metabolism of schistosomes is still far from being resolved, but I do
hope this discussion on internet will help to get a better picture of OUR worm.

Best regards, 
Louis Tielens


****************************************************************
Dr. A.G.M. Tielens
Laboratory of  Veterinary Biochemistry
Utrecht University
P.O.Box 80176
3508 TD Utrecht The Netherlands

tel:	(+31 30) 2535380
fax:	(+31 30) 2535492
e-mail:	tielens at biochem.dgk.ruu.nl

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