Figure 2. Cycles improve efficiency of energy transfer.

The three panels show six compound-conserved cycles, beginning with the circulation (first cycle on the left) and ending with the cross-bridges in the sarcomeres (last cycle on the right). There are four interlinked cycles in the mitochondria: the Krebs cycle, the NAD⁺/NADH-H⁺ and FAD⁺/FADH-H⁺ cycle, the build-up and collapse of the proton (H⁺) gradient across the inner mitochondrial membrane, and the ADP/ATP cycle. Release and reuptake of Ca²⁺ by the sarcoendoplasmic reticulum regulates cross-bridge formation in the sarcomeres and also regulates dehydrogenase activities of the Krebs cycle in the mitochondria. Panel A depicts a model of normal energy transfer (arrow on top of each panel). Panel B depicts a model of increased energy transfer in the adaptive response to an increase in workload of the heart. Panel C depicts a model of decreased energy transfer in the maladaptive state of heart failure. Note the feedback loop from crossbridges to the circulation (arrow on the bottom of each panel). In the text we propose that boosting the circulation (↑) with mechanical support may restore the flow of energy through the series of interconnected moiety-conserved cycles (lower panel).

Abbreviations: ADP, adenosine diphosphate; ATP, adenosine triphosphate; FAD, flavine adenine dinucleotide; FADH, reduced flavine adenine dinucleotide; NAD, nicotinamide adenine dinucleotide; NADH, reduced nicotinamide dinucleotide.