R,S-1,3-BUTANEDIOL ACETOACETATE ESTERS, POTENTIAL ALTERNATES TO LIPIDEMULSIONS FOR TOTAL PARENTERAL-NUTRITION

We present the preparation and characterization of totally and partial ly water-soluble forms of fat which could replace emulsions of long-ch ain triacylglycerols for total parenteral nutrition. R,S-1,3-butanedio l acetoacetate monoesters and diester represent pH-neutral, sodium-fre e, diffusible precursors of ketone bodies. The latter are water-solubl e forms of fat that are well used by peripheral tissues except in prol onged starvation and diabetic ketoacidosis. The esters are rapidly hyd rolyzed by plasma and tissue esterases. R,S-1,3-butanediol liberated i s oxidized in liver to R,S-beta-hydroxybutprate. Reducing equivalents generated during this oxidation are trapped in the conversion of aceto acetate to R-beta-hydroxybutyrate. So both the carbon and the hydrogen of the esters are exported from the liver to peripheral tissues in th e form of R- + S-beta-hydroxybutyrate. Thus, contrary to what occurs a fter administration of ethanol or R,S-1,3-butanediol alone, administra tion of the R,S-1,3-butanediol acetoacetate esters does not lead to ma jor shifts in the liver's [NADH]/[NAD(+)] ratio. Such shifts are respo nsible for the toxic effects of ethanol on the liver. It is therefore likely that long-term administration of the R,S-1,3-butanediol acetoac etate esters will not lead to liver toxicity.