George Albers-Schonberg

Phosphonomycin: Structure and Synthesis

Synthesis and resolution of the antibiotic phosphonomycin are described. The structure is (—)(IR, 2S)-1,2-epoxypropylphosphonic acid.

Avermectins, New Family of Potent Anthelmintic Agents: Isolation and Chromatographic Properties

The avermectins, a family of new anthelmintic agents, were isolated from the mycelia of Streptomyces avermitilis. Four closely related major components and four homologous minor components were separated from the complex. Solvent extraction, solvent partition, and adsorption methods were used to isolate and purify the complex; novel partition chromatography systems using Sephadex LH-20 were used to separate the components. A reverse-phase high-pressure liquid chromatography assay for the quantitative determination of all components was used extensively to monitor the purification methods.

Synthesis of ordinary and β-hydroxy fatty acids by heart mitochondria☆

Abstract The fatty acids (FA) synthesized from acetate by intact rabbit heart mitochondria were identified. These FA were mainly 12 to 16 carbons long. One-half were β-hydroxy FA, and mass spectrometric analysis after [1- 13 C)acetate incorporation showed them to be synthesized de novo . The latter were oxidized by the mitochondria with an ADP pulse, which means that they were L(+) isomers. β-Hydroxymyristate was the predominant endogenous saturated β-hydroxy FA detected in heart mitochondria. Only 10% of the product FA were esterified to coenzyme A and 4% were in phospholipid. Most of the FA were released from the mitochondria as free FA during incubation and were preferentially bound by serum albumin. Electron microscopy showed preservation of normal mitochondrial morphology. An ADP pulse caused prompt rapid oxidation only of the intramitochondrial labeled FA. The data confirm de novo FA synthesis in heart mitochondria and suggest the mechanism of reversal of the β-oxidation system. This process may have physiological importance by serving two functions: (1) the β-hydroxy FA, as CoA esters, could participate in an NADH “shuttle” to transfer cytoplasmic reducing equivalents into mitochondria; (2) FA synthesis could facilitate glycolysis during hypoxia by oxidizing NADH.