Submitted on February 11, 2009
Revised on June 5, 2009
Accepted on June 11, 2009
The Randle Cycle Revisited: A New Head for an Old Hat
Louis Hue1* and Heinrich Taegtmeyer2
1 Louvain University Medical School
2 University of Texas Medical School
* To whom correspondence should be addressed. E-mail: louis.hue{at}uclouvain.be.
In 1963 the Lancet published a paper by Randle, Garland, Hales and Newsholme, which proposed the 'glucose-fatty acid cycle' to describe fuel flux between and fuel selection by tissues. The original biochemical mechanism explained the inhibition of glucose oxidation by fatty acids. Since then the principle has been confirmed by many investigators. At the same time many new mechanisms controlling the utilization of glucose and fatty acids have been discovered. Here, we review the known short- and long-term mechanisms involved in the control of glucose and fatty acid utilization at the cytoplasmic and mitochondrial level in mammalian muscle and liver under normal and pathophysiological conditions. They include allosteric control, reversible phosphorylation and the expression of key enzymes. However, the complexity is formidable. We suggest that not all chapters of the Randle cyle have been written.
