Figure 5

Carbohydrate metabolism in daf-2 worms. Five signature metabolites - malate, acetate, succinate, glucose and trehalose - are linked by three major pathways: the glyoxylate shunt, gluconeogenesis, and starch metabolism. Expression data [20] shows that these three pathways (blue lines) are upregulated in daf-2(e1370) worms. Glycolysis and citric acid cycle genes (brown lines) are, by contrast, generally downregulated or unregulated. In this model, carbon from acetate or fatty acid metabolism enters the glyoxylate pathway mediated by increased expression isocitrate lyase (4.1.3.1) and malate synthase (4.1.3.2) which are encoded by a single gene, gei-7. The product of this pathway, malate, is then converted to oxaloacetate by cytosolic malate dehydrogenase (1.1.1.37) which then results, via gluconeogenesis, to the production of carbohydrates. The irreversible steps of gluconeogenesis are catalysed by phosphoenolpyruvate carboxykinase (4.1.1.32, PEPCK), pyruvate carboxylase (6.4.1.1), and fructose 1,6-biphosphatase (3.1.3.11). Most of the genes encoding components of these enzymes are upregulated in daf-2(-) worms. In most animals, glucose is synthesized from glucose-6-phosphate by glucose-6-phosphatase (3.1.3.9) but C. elegans does not contain a homologue of this gene. We suppose, then, that glucose is produced by the metabolism of trehalose by trehalase (3.2.1.28). Several trehalase genes are downregulated in daf-2 worms implying a reduced flux to glucose. However, glucose demand is also probably reduced since two genes encoding hexokinase (2.7.1.1), responsible for a irreversible reaction in glycolysis, are repressed in daf-2 worms as are many of the genes encoding the pyruvate dehydrogenase complex that links glycolysis to the citric acid cycle via acetyl-CoA. In contrast to the glyoxylate pathway genes, TCA genes are not generally regulated in daf-2(-) worms. Genes and metabolites are taken to be regulated if P = 0.05 (Additional file 2).