Figure 4.

The Randle cycle in RVH. The reciprocal relationship between GO and FAO is referred to as Randle's cycle. The production of citrate and acetyl CoA from β-oxidation inhibits HK1/2, PFK and PDH, thereby inhibiting glucose oxidation. In PAB-induced RVH, increased FAO inhibits GO. Conversely, FAO inhibitors (TMZ and Ran) increase PDH activity and restore GO. FAO: fatty acid oxidation; GO: glucose oxidation; Glut1: glucose transporter 1; HK1/2: hexokinase1/2; PFK: phosphofructokinase; LDHA: lactate dehydrogenase A; PDH: pyruvate dehydrogenase; FATP1: fatty acid transport protein 1; FA-CoA: fatty acyl-CoA; OMM and IMM: outer and inner mitochondrial membrane; CPT1 and CPT2: carnitine palmitoyltransferase I and II; TMZ: trimetazidine; RAN: ranolazine. The diagram is adapted from reference 34, with permission.