The Pentose-Phosphate Pathway
Glucose is also metabolized by a second pathway, different from glycolysis, the pentose-phosphate pathway (PPP), also known as the hexose-monophosphate shunt (Fig. 3). While the role of the EMP has been extensively investigated in T. brucei, there have been only a limited number of studies on the PPP and its contribution to carbohydrate metabolism. Although there have been doubts as to the functioning of this pathway it is now clear that it plays a crucial role both in the metabolism of T. brucei bloodstream forms and its protection against oxidant stress.
An important role of the pentose phosphate pathway is to maintain a pool of cellular NADPH, which serves as a hydrogen donor in reductive biosynthesis, and in the defence against oxidative stress. The PPP itself serves to convert glucose 6-phosphate (G6P) to ribose 5-phosphate (R5P), which is used in nucleotide biosynthesis. The oxidative branch of the pathway converts G6P to ribulose 5-phosphate (Ru5P), a process which leads to the production of two moles of NADPH per mole of G6P consumed. The non-oxidative branch generates from various pentose-phosphates the substrates for the enzymes transketolase and transaldolase which transfer, respectively, two- and three-carbon units, between a variety of phosphorylated carbohydrates. End products of the non-oxidative branch are the glycolytic intermediates fructose 6-phosphate (F6P) and glyceraldehyde 3-phosphate (GA3P). The latter branch may also function in the other direction, where GA3P and F6P are used to generate other phosphorylated sugars.
All the enzymes of the classical PPP have been detected in the procyclic form (Cronin et al., 1989). However, in the bloodstream form two enzymes of the non-oxidative pathway, ribulose-5-phosphate epimerase and transketolase, were not detected, while transaldolase was present. The classical enzymes appear to be predominantly cytosolic, but there is some evidence to suggest that part of the G6PD and 6PGD may be associated with glycosomes (Heise and Opperdoes unpublished). Rat-liver peroxisomes contain separate isoenzymes for G6PD and 6PGD, which are involved in the formation of NADPH required for peroxisomal alkoxyphospholipid biosynthesis. As this biosynthetic pathway is also present in glycosomes, this may be the explanation why small amounts of the oxidative branch dehydrogenases are found in these organelles.