Deranged energy substrate metabolism in the failing heart

2006 ◽  
Vol 8 (6) ◽  
pp. 465-471 ◽  
Author(s):  
Qi Tian ◽  
Philip M. Barger
Author(s):  
Jan F.C. Glatz ◽  
Miranda Nabben ◽  
Martin E. Young ◽  
P. Christian Schulze ◽  
Heinrich Taegtmeyer ◽  
...  

Author(s):  
Abdullah F. Alghannam ◽  
Mazen M. Ghaith ◽  
Maha H. Alhussain

The human body requires energy to function. Adenosine triphosphate (ATP) is the cellular currency for energy-requiring processes including mechanical work (i.e., exercise). ATP used by the cells is ultimately derived from the catabolism of energy substrate molecules—carbohydrates, fat, and protein. In prolonged moderate to high-intensity exercise, there is a delicate interplay between carbohydrate and fat metabolism, and this bioenergetic process is tightly regulated by numerous physiological, nutritional, and environmental factors such as exercise intensity and duration, body mass and feeding state. Carbohydrate metabolism is of critical importance during prolonged endurance-type exercise, reflecting the physiological need to regulate glucose homeostasis, assuring optimal glycogen storage, proper muscle fuelling, and delaying the onset of fatigue. Fat metabolism represents a sustainable source of energy to meet energy demands and preserve the ‘limited’ carbohydrate stores. Coordinated neural, hormonal and circulatory events occur during prolonged endurance-type exercise, facilitating the delivery of fatty acids from adipose tissue to the working muscle for oxidation. However, with increasing exercise intensity, fat oxidation declines and is unable to supply ATP at the rate of the exercise demand. Protein is considered a subsidiary source of energy supporting carbohydrates and fat metabolism, contributing to approximately 10% of total ATP turnover during prolonged endurance-type exercise. In this review we present an overview of substrate metabolism during prolonged endurance-type exercise and the regulatory mechanisms involved in ATP turnover to meet the energetic demands of exercise.


Shock ◽  
2020 ◽  
Vol 53 (2) ◽  
pp. 236-241
Author(s):  
Takayuki Irahara ◽  
Norio Sato ◽  
Kosuke Otake ◽  
Satoru Murata ◽  
Kazuo Inoue ◽  
...  

2007 ◽  
Vol 150 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Matti Virkkunen ◽  
Aila Rissanen ◽  
Hannu Naukkarinen ◽  
Anja Franssila-Kallunki ◽  
Markku Linnoila ◽  
...  

2003 ◽  
Vol 98 (2) ◽  
pp. 379-386 ◽  
Author(s):  
Barry A. Finegan ◽  
Manoj Gandhi ◽  
Matthew R. Cohen ◽  
Donald Legatt ◽  
Alexander S. Clanachan

Background Isoflurane enhances mechanical function in hearts subject to normothermic global or regional ischemia. The authors examined the effectiveness of isoflurane in preserving mechanical function in hearts subjected to cardioplegic arrest and prolonged hypothermic no-flow storage. The role of isoflurane in altering myocardial glucose metabolism during storage and reperfusion during these conditions and the contribution of adenosine triphosphate-sensitive potassium (K(atp)) channel activation in mediating the functional and metabolic effects of isoflurane preconditioning was determined. Methods Isolated working rat hearts were subjected to cardioplegic arrest with St. Thomas' II solution, hypothermic no-flow storage for 8 h, and subsequent aerobic reperfusion. The consequences of isoflurane treatment were assessed during the following conditions: (1) isoflurane exposure before and during storage; (2) brief isoflurane exposure during early nonworking poststorage reperfusion; and (3) isoflurane preconditioning before storage. The selective mitochondrial and sarcolemmal K(atp) channel antagonists, 5-hydroxydecanoate and HMR 1098, respectively, were used to assess the role of K(atp) channel activation on glycogen consumption during storage in isoflurane-preconditioned hearts. Results Isoflurane enhanced recovery of mechanical function if present before and during storage. Isoflurane preconditioning was also protective. Isoflurane reduced glycogen consumption during storage under the aforementioned circumstances. Storage of isoflurane-preconditioned hearts in the presence of 5-hydroxydecanoate prevented the reduction in glycogen consumption during storage and abolished the beneficial effect of isoflurane preconditioning on recovery of mechanical function. Conclusions Isoflurane provides additive protection of hearts subject to cardioplegic arrest and prolonged hypothermic no-flow storage and favorably alters energy substrate metabolism by modulating glycolysis during ischemia. The effects of isoflurane preconditioning on glycolysis during hypothermic no-flow storage appears to be associated with activation of mitochondrial K(atp) channels.


2016 ◽  
Vol 311 (4) ◽  
pp. H881-H891 ◽  
Author(s):  
Scott B. Crown ◽  
Joanne K. Kelleher ◽  
Rosanne Rouf ◽  
Deborah M. Muoio ◽  
Maciek R. Antoniewicz

In many forms of cardiomyopathy, alterations in energy substrate metabolism play a key role in disease pathogenesis. Stable isotope tracing in rodent heart perfusion systems can be used to determine cardiac metabolic fluxes, namely those relative fluxes that contribute to pyruvate, the acetyl-CoA pool, and pyruvate anaplerosis, which are critical to cardiac homeostasis. Methods have previously been developed to interrogate these relative fluxes using isotopomer enrichments of measured metabolites and algebraic equations to determine a predefined metabolic flux model. However, this approach is exquisitely sensitive to measurement error, thus precluding accurate relative flux parameter determination. In this study, we applied a novel mathematical approach to determine relative cardiac metabolic fluxes using 13C-metabolic flux analysis (13C-MFA) aided by multiple tracer experiments and integrated data analysis. Using 13C-MFA, we validated a metabolic network model to explain myocardial energy substrate metabolism. Four different 13C-labeled substrates were queried (i.e., glucose, lactate, pyruvate, and oleate) based on a previously published study. We integrated the analysis of the complete set of isotopomer data gathered from these mouse heart perfusion experiments into a single comprehensive network model that delineates substrate contributions to both pyruvate and acetyl-CoA pools at a greater resolution than that offered by traditional methods using algebraic equations. To our knowledge, this is the first rigorous application of 13C-MFA to interrogate data from multiple tracer experiments in the perfused heart. We anticipate that this approach can be used widely to study energy substrate metabolism in this and other similar biological systems.


Metabolism ◽  
1990 ◽  
Vol 39 (8) ◽  
pp. 876-881 ◽  
Author(s):  
T.P. Stein ◽  
C. Nutinsky ◽  
D. Condoluci ◽  
M.D. Schluter ◽  
M.J. Leskiw

2019 ◽  
Vol Volume 15 ◽  
pp. 659-668 ◽  
Author(s):  
Jia Yao ◽  
Weijia Han ◽  
Xiaojing Ren ◽  
Lili Yuan ◽  
Jun Xu ◽  
...  

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