Fig. 1: Cellular energy metabolism: Linkage of OXPHOS to catabolic pathways for glucose, fatty acids, and glutamine.
From: Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia
Cells use OXPHOS to generate ATP, through the interlinkage of TCA cycle and electron transport chain (ETC). TCA cycle supplies NADH and FADH2 to the ETC. Electrons are donated by NADH to complex I and by FADH2 to complex II, then transferred to coenzyme Q, to complex III, to cytochrome c and finally to complex IV. This electron transport allows a series of oxidation and reduction reactions within complexes I, II and IV, which in turns allows these complexes to transfer hydrogen protons from inside the mitochondria to the mitochondrial intermembrane space. The accumulation of protons in this space creates a difference in the charge between the inner mitochondria and its intermembrane space. This mitochondrial potential allows protons to flow back into the mitochondria through complex V, providing the energy to bond an inorganic phosphate to a molecule of ADP, producing ATP. Glycolysis is the metabolic process in which glucose is converted into pyruvate, which can then convert pyruvate into acetyl-CoA used in TCA cycle, hence in OXPHOS. One molecule of fructose-6P yields two glyceraldehyde 3-P, thus, one molecule of glucose can yield two molecules of pyruvate. Fatty acid metabolism can also supply the TCA cycle with acetyl-CoA through the fatty acid β-oxidation. Glutamine metabolism is the process in which glutaminase (GLS) converts glutamine to glutamate, which can then be passed into the mitochondrion through the glutamate shuttle and can be converted into α-ketoglutarate, further supplying TCA cycle and enhance OXPHOS activity. (GLS: glutaminase; IDH2: isocitrate dehydrogenase: Lactate DH: lactate dehydrogenase; PFK: phosphofructokinase).
