title: Synthesis and intravenous infusion into the rat of glyceryl bisacetoacetate, 1-acetoacetamido-2, 3-propane diol, and partially reduced glucosyl pentaacetoacetate.
abstract: The efficacy of parenteral nutrition could be improved by finding a more effective energy source. Esters of short-chain fatty acids have exhibited some promise as alternatives to glucose. The present study reports on two new esters and one amide, each containing acetoacetate as the organic acid. The three compounds: glyceryl bisacetoacetate, N-2',3'-dihydroxypropyl-3-oxo-butanamide (1-acetoacetamido-2,3-propane diol), and partially reduced glucosyl pentaacetoacetate, were synthesized and then continuously infused into rats for 7 d. The infusion rate provided 50% of the rats' estimated metabolic energy requirements, and rats were fed with a reduced-energy oral diet that provided the remaining 50% of energy plus adequate protein. Rat groups for each compound were: (1) experimental-compound-infused and ad libitum-fed, (2) isoenergetic glucose-infused and pairfed, and (3) saline infused and pair-fed. Body-weight changes, N losses and N retention were measured daily. All rats died from partially reduced glucosyl pentaacetoacetate infusion at 100% and 50% of the intended rate. Rats infused with 1-acetoacetamido-2,3-propane diol failed to gain weight and to increase the plasma ketone-body concentration. Glyceryl bisacetoacetate produced hyperketonaemia, and weight gain and N variables that were similar to those for glucose-infused rats. It was concluded that only glyceryl bisacetoacetate would make a satisfactory parenteral nutrient.
authors.affiliation: Department of Surgery, Medical College of Ohio, Toledo, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Birkhahn
authors.forename: R J
authors.initials: RJ
authors.lastname: Clemens
authors.forename: J C
authors.initials: JC
authors.lastname: Hubbs
mesh_terms: D000090:Acetoacetates / Q000008:administration & dosage* / Q000138:chemical synthesis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004734:Energy Metabolism; D005526:Food, Formulated; D007262:Infusions, Intravenous; D008297:Male; D009584:Nitrogen / Q000378:metabolism / Q000652:urine; D010288:Parenteral Nutrition; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000090:Acetoacetates; D009584:Nitrogen