Regulation of carbohydrate metabolism during Giardia encystment.
Giardia intestinalis trophozoites encyst when they are exposed to bile. During encystment, events related to the inducible synthesis of a novel N-acetyl-D-galactosamine (GalNAc) homopolymer, occur. Within the first 6 h of encystment, mRNA for glucosamine 6-P isomerase (GPI), the first inducible enzyme unique to this pathway appears, oxygen uptake rates double from non-encysting levels, and metronidazole (MTZ) inhibits oxygen uptake. Within 12 h, GPI and its activity are detectable and OU decreases 50% from non-encysting levels; glucose's stimulation and MTZ's inhibition of oxygen uptake cease. In contrast, aspartate uptake remained constant throughout the 40 h monitored. Two genes, gpi 1 and 2 encode for GPI, but only gpi1 is expressed during encystment. Glucosamine 6-P (GlcN6P), the synthetic product of GPI, activates UDP-N-acetylglucosamine (UDP-GlcNAc) pyrophosphorylase, a downstream enzyme, 3 to 5-fold in the direction of UDP-GlcNAc synthesis. UDP-GlcNAc is epimerized to UDP-GalNAc and UDP-GalNAc is polymerized by "cyst wall synthase" (beta 1 --> 3 GalNAc transferase) into a highly insoluble beta 1,3-linked homopolymer. This GalNAc polysaccharide, the major component of cyst wall filaments, forms, in conjunction with polypeptides, the outer cyst wall of Giardia.
Jarroll
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Department of Biology, Northeastern University, Boston, Massachusetts 02115, USA. ejarroll@lynx.neu.edu
Macechko
P T
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Steimle
P A
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Bulik
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D
Karr
C D
CD
van Keulen
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Paget
T A
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Gerwig
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Kamerling
J
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Vliegenthart
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Erlandsen
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D000116:Acetylgalactosamine / Q000235:genetics / Q000378:metabolism*; D019747:Aldose-Ketose Isomerases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D015971:Gene Expression Regulation, Enzymologic; D017125:Genes, Protozoan; D016829:Giardia lamblia / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D005873:Giardiasis / Q000469:parasitology; D006801:Humans; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000378:metabolism*
D011134:Polysaccharides; C020582:glucosamine-6-phosphate isomerase; D019747:Aldose-Ketose Isomerases; D000116:Acetylgalactosamine