Heart design: free ADP scales with absolute mitochondrial and myofibrillar volumes from mouse to human

Biochim Biophys Acta. 2002 Feb 15;1553(3):261-7. doi: 10.1016/s0005-2728(01)00247-x.

Abstract

Our aim was to estimate a number of bioenergetic parameters in the beating mouse, rat and guinea pig heart in situ and compare the values to those in hearts of mammals over a 2000-fold range in body mass. For the mouse, rat and guinea pig heart, we report a phosphorylation ratio of 1005+/-50 (n=16), 460+/-32 (n=10) and 330+/-22 (n=5) mM(-1) and a free cytosolic [ADP] concentration of 13, 18 and 22 microM, respectively. When each parameter was plotted against body mass, they scaled closely to the quarter power (-0.28, r=0.99 and -0.23, r=0.97). A similar regression slope was found when the inverse of free [ADP] was plotted against absolute mitochondrial (slope=-0.26, r=0.99) and myofibrillar volumes (slope=-0.24, r=0.99). The similar slopes indicate that the ratio of absolute mitochondria and myofibrillar volumes in the healthy mammalian heart is a constant, and independent of body size. In conclusion, our study supports the hypothesis that the mammalian heart has a number of highly conserved thermodynamic and kinetic parameters that obey quarter-power laws linking the phosphorylation ratio, ATP turnover rates, free [ADP] and absolute mitochondrial volumes to body size. The results are discussed in terms of possible mechanisms and potential deviations from these laws in some disease states.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / analysis
  • Adenosine Diphosphate / metabolism*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Body Weight
  • Cardiac Output
  • Cytosol / metabolism
  • Energy Metabolism*
  • Guinea Pigs
  • Heart / anatomy & histology
  • Heart / physiology*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mitochondria, Heart / metabolism*
  • Organ Size
  • Phosphorylation
  • Rats
  • Regression Analysis

Substances

  • Adenosine Diphosphate
  • Adenosine Triphosphate