Giardia Metabolism

Abstract

This chapter describes key aspects of our basic knowledge of Giardia metabolism. It is well known that this organism has minimal biosynthetic capacity: it lacks de novo lipid, de novo purine, and de novo pyrimidine syntheses (relying solely on salvage pathways). Giardia also lacks mitochondria and cytochrome-mediated oxidative phosphorylation and thus trophozoites use glycolysis (from glucose only) and the arginine dihydrolase pathways relying on substrate level phosphorylation for energy production; glucose is also shunted through a pentose phosphate pathway. The enzymes responsible for end product and energy production in Giardia are soluble—not found in subcellular organelles. The end products of glucose fermentation are acetate, ethanol, alanine, carbon dioxide, and hydrogen. Thus, it is clear that Giardia is well adapted to its environment; however, this comes at a cost because this organism must scavenge nearly all of its biosynthetic pre-cursors from an environment containing a thriving microbial flora. Additionally, Giardia’s metabolism seems to be exquisitely balanced — and this would mean that processes such as the formation of the cyst wall carbohydrate have to be tightly controlled and regulated: encysting Giardia slows their catabolism of glucose for energy, and begin converting glucose to the synthesis of a cyst wall specific sugar, N- acetylgalactosamine, for the synthesis of giardan. A complete pathway of enzymes is induced during encystment for this synthesis including a novel enzyme, cyst wall synthase, that synthesized the giardanhomopolymer [β-1,3-N-acetylgalactosamine]n. At the same time, trophozoites increase their catabolism of arginine ostensibly to offset the energy lost from slowing glycolysis.Also highlighted in this chapter is the fact that most studies on the metabolism, proteomics, and transcriptomics have been performed on a limited number of isolates, and there are few reports detailing comparative studies of metabolism and biochemistry of isolates. Those studies do indicate metabolic differences among isolates and comparative metabolic studies of genetically distinct isolates are vital to understanding how Giardia survives in the gut and responds to changes in this environment. Variation in metabolism may also be responsible for variation in reproduction rates and virulence among isolates.