Year: 2012
Type: review
Abstract: The heart is nearly unique in the body in that it has a constant workload well beyond the normal maintenance of cellular integrity.In addition, the heart of a large animal such as man also has the capacity to increase its workload by nearly 10-fold for considerable amounts of time.A high steady state and peak work demand require the heart to use the space-and weightefficient mitochondria to provide an adequate energy conversion rate to support these activities.The heart's energy conversion results in remarkably high metabolite turnover rates (i.e., time to turnover the entire metabolite pool), with values ranging from resting to maximum workloads of 10-2 s for ATP, 170-40 ms for ADP, and 250-70 ms for mitochondrial nicotinamide adenine dinucleotide (NADH) (Mootha et al., 1997;Balaban, 2002).With this requirement for a constant workload coupled to large sustained changes in dynamic range, it is not surprising that cardiac energy conversion is highly specialized.As seen from the metabolic pool turnover estimates above, a slight mismatch between energy conversion rates and workload could severely impact metabolite levels in seconds.Thus, tight temporal coupling between mitochondrial energy conversion and heart workload is an absolute requirement of the metabolic control network.In addition, because oxygen extraction from the coronary vasculature is nearly complete, a tight coupling of coronary blood flow control to heart workload is important.Taking these data into consideration, it is not surprising that there is a linear relationship between the rate of mitochondrial respiration, blood flow, and workload (Starling and Visscher, 1927;Gutterman and Cowley, 2006).Remarkably, the heart is able to accomplish this over a wide workload range with very little change in the steady-state concentrations of ATP, ADP, and NADH associated with this energy conversion process, despite the approximately100-ms turnover of some metabolite pools.Even the metabolites creatine phosphate (CrP)
Author: Robert S. Balaban
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2132037876