Energy metabolism disorders and potential therapeutic drugs in heart failure

Figures

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  Figure 1. The energy metabolism process of fatty acid, glucose and ketone body. Various metabolic substrates are transported to the cytoplasm to form corresponding intermediate product, such as pyruvate, fatty acyl CoA, etc. These intermediates enter the mitochondrial matrix through a specific transport system and generate NADH, FADH2, GTP through the TCA cycle, fatty acid oxidation and other pathways. Then NADH and FADH2 produce ATP through the electron transfer chain, which provides energy for cardiomyocytes.

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  Figure 2. Energy produce of glucose (A) and fatty acid (B) oxidation. In an ideal state, 1 mol glucose is converted into 2 mol pyruvic acid and 2 mol NADH. 1 mol pyruvic acid can produce 1 mol acetyl CoA and 1 mol NADH. 1 mol acetyl CoA can generate 1 mol ATP, 3 mol NADH and 1 mol FADH2 after one TCA cycle. 1 mol NADH and FADH2 can generate corresponding 2.5 mol ATP and 1.5 mol ATP through electron chain transfer respectively. 1 mol glucose is completely oxidized to produce 30 mol ATP. 1 mol fatty acid (20C) consumes 2 ATP can produce 1 mol fatty acyl CoA (20C). After β oxidation, 10 mol of acetyl-CoA can be generated by 1 mol fatty acyl CoA (20C), and then enter the TCA cycle. Therefore, 1 mol of fatty acid can be completely oxidized to generate 134 mol of ATP.

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  Figure 3. AMPK and mTOR signaling pathway. When energy is insufficient, AMPK can be activated to increase the intake of fatty acids and glucose, inhibit glycogen synthesis, promote fatty acid oxidation and increase energy production. At the same time, it can promote the synthesis of mitochondria by regulating PGC-α. AMPK activation, hypoxia conditions and insulin can also inhibit mTORC1 activation, so as to regulate fatty acid metabolism, protein synthesis, autophagy, etc. Insulin can also directly activate mTORC2, regulate cell survival and cytoskeleton formation.