Pyruvate exerts several effects that could prove beneficial to humans, including improved function of failing heart, enhanced effectiveness of insulin to control blood sugar levels, reduction in amount of fat tissue, and increased lean muscle mass.  These effects of pyruvate could assist in the treatment of congestive heart failure, diabetes, and obesity and thus favorably impact the lives of millions of Americans, especially if pyruvate could be conveniently administered as a dietary supplement.  Unfortunately, pyruvate consumed orally does not reach the organs it could potentially benefit.  To enter the systemic bloodstream, substances consumed in the diet must be absorbed from the gut by special cells that line the gut and must pass through the liver, a metabolically active organ that heavily modifies dietary substances.  Both the gut lining and liver can transform pyruvate to other compounds that lack its beneficial properties.  For dietary pyruvate to be an effective treatment, it must pass through the gut lining and liver without being metabolized.

          Our objective is to protect pyruvate from gut and liver metabolism, making it accessible to heart, brain and other vital organs.  This aim will be accomplished by chemically linking pyruvate to amino acids, the building blocks of proteins, to form pyruvate-amino acid conjugates and administering these novel compounds to rats and guinea-pigs in the diet.  Co-investigator John Ivy has demonstrated that such chemical modification enables pyruvate to traverse the gut and liver and enter the systemic bloodstream intact.  Heart, muscle and brain cells take up the pyruvate-amino acid compound and break the chemical link between pyruvate and amino-acid to release pyruvate within the cells.  Thus, the amino acid will serve to shield pyruvate from metabolism until it reaches the target organs where it can exert its beneficial effects.

          In this investigation, novel chemical derivatives of pyruvate will be developed that enable pyruvate to traverse the metabolic barriers imposed by the intestinal lining and liver and thereby gain access to vital organs.  The ability of daily dietary consumption of pyruvate-amino acid conjugates to produce beneficial effects on the body, including metabolic protection of the heart, reduction of fat tissue, increased lean muscle mass, and augmentation of insulin control of blood sugar will be characterized.  It is anticipated that the novel compounds developed in this investigation could potentially benefit millions of people suffering from heart disease, diabetes and obesity.

© Cardiovascular Research Institute, February 2000
An Institute of Discovery at the University of North Texas Health Science Center at Fort Worth