Lipid emulsions used extensively for parenteral nutrition have undesirable side effects which are, in part, caused by the insolubility of fat in water. We would like to explore the potential of 1,3-butanediol and 1,3-pentanediol either as DL mixtures or as L-isomers, as fuels for intravenous nutrition. These diols are water soluble and non-ionized. They are at the same time carbohydrates and lipid precursors. D-1,3-butanediol is metabolized to physiological ketone bodies D-3-hydroxybutyrate and acetoacetate. Ketone bodies are excellent fuels for peripheral tissues. The other diols (L-1,3-butanediol, D and L-1,3-pentanediol) are oxidized to hydroxyacids which are analogs of physiological D-3-hydroxybutyrate. Ultimately the diols are converted to acetyl-CoA (butanediol) or acetyl-CoA + propionyl-CoA (pentanediol). Propionyl-CoA is a gluconeogenic precursor in liver and an anaplerotic substrate in all tissues. There is good reason to hypothesize that the diols, in particulr the L-diols, are a good source of calories for parenteral nutrition. The investigations for which support is sought will study the metabolism of the diols and of the corresponding hydroxyacids in perfused livers and hearts from rats. We shall also conduct intravenous infusion studies on live rats and dogs. We hope that these studies will generate the biochemical and physiological basis for clinical trials on human to be conducted in a subsequent project.
Showing the most recent 10 out of 62 publications
