Figure 4: Pathways of non-oxidative glucose metabolism whose by-products contribute to cardiac remodeling.

Schematic summary of glucose uptake via GLUT1 and GLUT4 transporters and entry of glucose into the glycolytic pathway (purple arrows) leading to the generation of pyruvate. In heart failure, impaired entry of pyruvate into mitochondria or decreased mitochondrial pyruvate metabolism leads to accumulation of glycolytic intermediates and increased flux into accessory pathways (blue arrows) such as the polyol pathway, pentose phosphate pathway, hexosamine biosynthetic pathway, mannose and galactosamine synthetic pathways and one carbon metabolism pathways, products of which have been linked to the activation of signaling pathways that may contribute to left ventricular modelling. Regulatory steps in glycolysis that have been implicated in heart failure include phosphofructokinase (PFK), pyruvate kinase (PKM1), the mitochondrial pyruvate carrier (MPC) and pyruvate dehydrogenase (PDH). (Illustration credit: Ben Smith).