schisto glucose transport

[Shoemaker, Chuck]

Dear members of the Schistonet community,

     Many important issues have arisen in the literature concerning glucose 
uptake and metabolism in schistosomes.  We would like to initiate a 
discussion within the schisto community to consider all of the data and 
current opinion related to these issues.  The following are a few of the 
issues that we suggest as a starting point for discussion.  For each issue, 
we follow with a brief summary of selected relevant results from the 
literature, some of our own results where they contribute, and some proposed 
questions to discuss:

Issue 1.  How is sugar taken up by schistosomes from the host?  Early work 
showed that adults consume huge quantities of host hexose which is taken up 
across the adult schistosome tegument.  Some controversy remains whether 
uptake is entirely by passive diffusion or has an active transport 
component.  Other work indicated that males absorb sugar and pass it to 
females.  We have identified two functional schistosome facilitated 
diffusion glucose transporters that localize in the tegument, a basal 
membrane transporter, SGTP1, and an apical membrane transporter, SGTP4 
(PNAS, in press).  SGTP4 protein is rapidly synthesized and deposited on the 
somula surface coincident with cercarial transformation.  It is located 
within both bilayers of the apical membrane, at least in adults (EP, in 
press).  Males and females appear to have similar levels of these 
transporters distributed equally on the dorsal and ventral surfaces.  Our 
results therefore indicate that a single facilitated glucose transporter 
could be responsible for movement from host blood into the tegumental 
cytoplasm.   Based on the similar distribution of glucose transporters (and 
glucose metabolic enzymes) within males and females, our data do not support 
(nor rule out) the transfer of glucose from males to females.  Suggested 
discussion questions:

A.  Do schistosomes use active transport to absorb sugar from the host?

B.  Do schistosomes take up any glucose via the gut?  In vivo?

C.  Do females need males to obtain much of their glucose, and if so, why?


Issue 2:  What happens to the host glucose after absorption from the host?
Clearly glucose must be phosphorylated by hexokinase to trap it within the 
parasite and some results suggest that hexokinase is the rate limiting step 
in glucose metabolism.  We find that SGTP1 is localized in the basal 
membranes of the tegument and underlying muscle, suggesting that a part of 
the glucose transported through the apical membrane remains unphosphorylated 
until it is transported again through the basal membrane.   Certainly a 
significant share of glucose is needed by the tegument for protein and 
membrane biosynthesis and some is needed internally such as by muscle and 
reproduction organs.  But schistosomes are thought to lack a body fluid and, 
as most tissues (with the exception of the vitellaria and the gonads) are 
reportedly syncytial, the mechanism of internal nutrient distribution 
remains unclear.  This topic is complicated by the large, metabolically 
active glycogen reserves present in the parasites.  Suggested discussion 
questions:

A.  Where in the worm, and in what proportion, is the glucose utilized?

B.  How is glucose passed between the internal tissues of the worm?

C.  What is the function of glycogen in adult schistosomes?


Issue 3: How do schistosomes metabolize glucose at different stages and why? 
 Cercariae clearly perform oxidative glucose metabolism and newly 
transformed somula do not.  Early reports suggested that adults used only 
anaerobic glucose fermentation, but more recent data supports the use of 
oxidative metabolic processes in adults.  Suggested discussion questions:

A.  How does it benefit schistosomes to shut down oxidative metabolism upon 
cercarial transformation?

B.  How does it benefit adults to use limited (at best) oxidative glucose 
metabolism?


     We hope interested members of the schisto community will contribute to 
a dialogue on these issues and add additional issues to the discussion.


Dr. Patrick J. Skelly and Dr. Charles B. Shoemaker
Department of Tropical Public Health, Harvard School of Public Health