Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-10T11:42:03.588Z Has data issue: false hasContentIssue false

Synthesis and intravenous infusion into the rat of glyceryl bisacetoacetate, 1-acetoacetamido-2, 3-propane diol, and partially reduced glucosyl pentaacetoacetate

Published online by Cambridge University Press:  09 March 2007

Ronald H Birkhahn
Affiliation:
Department of Surgery, Medical College of Ohio, Toledo, OH, USA
Robert J Clemens
Affiliation:
Eastman Chemical Company, Kingsport, TN, USA
John C Hubbs
Affiliation:
Eastman Chemical Company, Kingsport, TN, USA
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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 7d. The infusion rate provided 50% of the rats' estimated metabolic energy requirement, 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 l-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.

Type
General Nutrition
Copyright
Copyright © The Nutrition Society 1997

References

REFERENCES

Bach, A. C. & Babayan, V. K. (1982). Medium chain triglycerides: an update. American Journal of Clinical Nutrition 36, 950962.CrossRefGoogle ScholarPubMed
Bailey, J. W., Barker, R. L. & Karlstad, M. D. (1992). Total parenteral nutrition with short-chain and long-chain triglycerides - triacetin improves nitrogen balance in rats. Journal of Nutrition 122, 18231829.CrossRefGoogle ScholarPubMed
Birkhahn, R. H. (1982). Experience with alternative fuels. In Advances in Clinical Nutrition, Proceedings of the 2nd International Symposium, pp. 325337 [Johnston, I. D. A., editor]. Boston, MA: MTP Press.Google Scholar
Birkhahn, R. H., Askari, A. & Thomford, N. R. (1986). Total parenteral feeding of rats with an acetoacetate monoglyceride and glucose mixture. Journal of Nutrition 116, 851864.CrossRefGoogle ScholarPubMed
Birkhahn, R. H., Awad, S., Klaunig, J. E. & Thomford, N. R. (1989). Interaction of ketosis and liver regeneration in the rat. Journal of Surgical Research 47, 427432.CrossRefGoogle ScholarPubMed
Birkhahn, R. H. & Border, J. R. (1978). Intravenous feeding of the rat with short chain fatty acid esters. II. Monoacetoacetin. American Journal of Clinical Nutrition 31, 436441.CrossRefGoogle ScholarPubMed
Birkhahn, R. H. & Border, J. R. (1981). Alternate or supplemental energy sources. Journal of Parenteral and Enteral Nutrition 5, 2431.Google ScholarPubMed
Birkhahn, R. H., McMenamy, R. H. & Border, J. R. (1979). Monoglyceryl acetoacetate: a ketone bodycarbohydrate substance for parenteral feeding of the rat. Journal of Nutrition 109, 11681174.CrossRefGoogle Scholar
Birkhahn, R. H. & Robertson, L. A. (1984). Parenteral feeding at two hypocaloric levels for comparison of glucose-glycerol mixture with the monoglyceride of acetoacetate on urinary nitrogen losses. Journal of Nutrition 114, 15941601.CrossRefGoogle ScholarPubMed
Border, J. R., Burns, G. P., Rumph, C. & Schenk, W. G. Sr (1970). Carnitine levels in severe infection and starvation: a possible key to the prolonged catabolic state. Surgery 68, 175183.Google Scholar
Brennan, M. F., Fitzpatrick, G. F., Cohen, K. H. & Moore, F. D. (1975). Glycerol: major contributor to the short term protein sparing effect of fat emulsions in normal man. Annals of surgery 182, 386394.CrossRefGoogle Scholar
Cahill, G. F. (1981). Ketosis. Journal of Parenteral and Enteral Nutrition 5, 281287.CrossRefGoogle Scholar
Clemens, R. J. (1984). The chemistry of the diketene-acetone adduct. Kodak Laboratory Chemical Bulletin 55, 14.Google Scholar
Desrochers, S., Dubreuil, P., Brunet, J., Jette, M., David, F., Landau, B. R. & Brunengraber, H. (1995). Metabolism of (R,S)-l,3-butanediol acetoacetate esters, potential parenteral and enteral nutrients in conscious pigs. American Journal of Physiology 268, E660E667.Google Scholar
Elam, E. U. & Middleton, M. L. (1985). United States Patent 4, 521,523.Google Scholar
Glantz, S. A. (1992). Primer of Bio-statistics, 3rd ed. New York: McGraw-Hill, Inc.Google Scholar
Hauschildt, S., Chalmers, R. A., Lawson, A. M., Schultis, K. & Watts, R. W. E. (1976). Metabolic investigations after xylitol infusions in human subjects. American Journal of Clinical Nutrition 29, 258273.CrossRefGoogle ScholarPubMed
Heyman, E. (1980). Carboxylesterases and amidases. In Enzymatic Basis of Detoxicarion, vol. 2, pp. 291323 [Jakoby, W. B., editor]. New York: Academic Press, Inc.CrossRefGoogle Scholar
Holecek, M. & Simek, J. (1985). Effect of glucose, fructose, sorbitol and amino acid solutions employed in clinical medicine on the development of liver regeneration after partial hepatectomy. Physiologia Bohemoslovaca 34, 395402.Google ScholarPubMed
Kripke, S. A., Fox, A. D., Berman, J. M., Depaula, J., Birkhahn, R. H. & Rombeau, J. L. (1988). Inhibition of TPN-associated intestinal mucosal atrophy with monoacetoacetin. Journal of Surgical Research 44, 426444.CrossRefGoogle ScholarPubMed
Leveen, H. H., Papps, G. & Restuccia, M. (1950). Problems in the intravenous administration of synthetic and natural fats for nutritional purposes. American Journal of Digestive Diseases 17, 2024.CrossRefGoogle ScholarPubMed
Maiz, A., Moldawer, L. L., Bistrian, B. R., Birkhahn, R. H., Long, C. L. & Blackburn, G. L. (1985). Monoacetoacetin and protein metabolism during parenteral nutrition in burned rat. Biochemical Journal 226, 4350.CrossRefGoogle Scholar
Nagayama, M., Thomford, N. R. & Birkhahn, R. H. (1990). Feeding the rat intravenously with ketone bodies following colon anastomosis. Journal of Parenteral and Enteral Nutrition 14, 245249.CrossRefGoogle ScholarPubMed
Ulrich, H., Pastores, S. M., Katz, D. P. & Kvetan, V. (1996). Parenteral use of medium-chain triglycerides: a reappraisal. Nutrition 12, 231238.CrossRefGoogle ScholarPubMed
Wells, F. E. & Smits, B. J. (1978). Utilization and metabolic effects of a solution of amino acids, sorbitol and ethanol in parenteral nutrition. American Journal of Clinical Nutrition 31, 442450.CrossRefGoogle ScholarPubMed