Hermann Dugas

R,S-1,3-butanediol acetoacetate esters, potential alternates to lipid emulsions for total parenteral nutrition

Abstract We present the preparation and characterization of totally and partially water-soluble forms of fat which could replace emulsions of long-chain triacylglycerols for total parenteral nutrition. R,S-1,3-butanediol acetoacetate monoesters and diester represent pH-neutral, sodium-free, diffusible precursors of ketone bodies. The latter are water-soluble forms of fat that are well used by peripheral tissues except in prolonged starvation and diabetic ketoacidosis. The esters are rapidly hydrolyzed by plasma and tissue esterases. R,S-1,3-butanediol liberated is oxidized in liver to R,S-β-hydroxybutyrate. Reducing equivalents generated during this oxidation are trapped in the conversion of acetoacetate to R-β-hydroxybutyrate. So both the carbon and the hydrogen of the esters are exported from the liver to peripheral tissues in the form of R- + S-β-hydroxybutyrate. Thus, contrary to what occurs after administration of ethanol or R,S-1,3-butanediol alone, administration of the R,S-1,3-butanediol acetoacetate esters does not lead to major shifts in the livers [NADH] [NAD + ] ratio. Such shifts are responsible for the toxic effects of ethanol on the liver. It is therefore likely that long-term administration of the R,S-1,3-butanediol acetoacetate esters will not lead to liver toxicity.

Catalase activity measurement with the disk flotation method

Activity measurements of catalase are usually performed with a spectrophotometric method by monitoring the decrease of H2O2 at 240 nm. A different method presented here uses an instrument named Catalase-meter and yields flotation time data which are expressed in tenth of seconds. For the first time, solutions of catalase of different concentrations were tested simultaneously with the two methods, and the Catalase-meters flotation data were submitted to correlation with international units calculated from spectrophotometric data. The corresponding calibration curve correlates flotation time data to international units. The r2 values thus obtained for the two calibration curves were 0.960 and 0.929, for a range of activity varying from 9.3 to 144.5 international units/ml.

Bioorganic Chemistry of the Amino Acids

Bioorganic chemistry provides a link between the work of the organic chemist and biochemist, and this chapter is intended to serve as a link between organic chemistry, biochemistry, and protein and medicinal chemistry or pharmacology. The emphasis is chemical and one is continually reminded to compare and contrast biochemical reactions with mechanistic and synthetic counterparts. The organic synthesis and biosynthesis of the peptide bond and the phosphate ester linkage (see Chapter 3) are presented “side-by-side”; this way, a surprising number of similarities are readily seen. Each amino acid is viewed separately as an organic entity with a unique chemistry. Dissociation behavior is related in terms of other organic acids and bases, and the basic principles are reviewed so that one is not left with the impression of the amino acid as being a peculiar species. The chemistry of the amino acids is presented as if part of an organic chemistry text, (alkylations, acylations, etc.), and biochemical topics are then discussed in a chemical light.

Introduction to Bioorganic Chemistry

Among the first persons to develop biooriented organic projects was F.H. Westheimer, in the 1950s. He was probably the first physical organic chemist to do serious studies of biochemical reactions. However, it was only twenty years later that the field blossomed to what is now accepted as bioorganic chemistry.

Bioorganic Chemistry of Amino Acids and Polypeptides

Bioorganic chemistry provides a link between the work of the organic chemist and biochemist, and this chapter is intended to serve as a link between organic chemistry, biochemistry, and protein and medicinal chemistry or pharmacology. The emphasis is chemical and one is continually reminded to compare and contrast biochemical reactions with mechanistic and synthetic counterparts. The organic chemistry of the peptide bond and the phosphate ester linkage (see Chapter 3) are presented “side by side”; this way, a surprising number of similarities are readily seen.

Bioorganic Chemistry of the Phosphates

Too often a detailed description of the synthesis and properties of peptides is given without consideration of the analogous, but equally important, synthesis and properties of phosphodiesters, and vice versa. Indeed many of the problems and strategies (i.e., use of DCC, common protecting groups, polymeric synthesis, etc.) are similar, if not the same, yet they are never presented “side-by-side.” It is with this purpose in mind that this chapter is written. Again, for the sake of comparison, biological synthesis of the phosphate bond is also presented. As such, a chemical and biological comparison (bioorganic) of the two functionally important classes of macro-molecules, the proteins and the nucleic acids, are presented. Of course, the picture is completed by examining two mononucleotides which are essential to the biological process: nucleoside triphosphates and cyclic nucleotides. This emphasizes that, as with the amino acids, not only polymers are important to the biological system. Again, a novel comparison of the chemical and biological synthesis is presented. This includes material which has been made available as recently as 1980.