Schoenheimer

The isotope dilution principle, first employed by Hevesy and Hobbie (133) in 1932 for the determination of lead in ores, was applied by Schoenheimer et al. (241) to the determination of amino acids. [Shemin and Foster (248) have reviewed this topic.] An N15-amino acid derivative was added to a protein hydrolyzate, a sample of the amino acid to be determined was isolated and purified, the excess N15 in this product was estimated with the mass spectrograph, and the grams of amino acid originally present were calculated from Equation 2. 

In 1933, Schoenheimer, who was medically qualified and had been working with Aschoff in the Pathology Institute in Freiburg, moved to Columbia University, New York, and was joined the next year by David Rittenberg. Rittenberg had just spent some time in Urey s laboratory in the Rockefeller Institute learning techniques for handling deuterium. Their first experiments concerned the metabolism of deuterated fatty acids in rats and the demonstration (see below) that 2H from heavy water was incorporated by the animals into fatty acids and cholesterol. 

If 15N ammonium citrate was administered, and glutamate, aspartate, and glycine isolated from liver and intestinal wall protein, all showed 15N uptake. From the results of labeling studies, Schoenheimer finished his Edward K.Dunham lectures in Harvard in 1941 with the phrase— the structural materials [of the body] are in a steady state of flux. The classical picture must thus be replaced by one which takes account of the dynamic state of body structure —an idea which has become an integral part of biochemistry since that time, and which was almost totally dependent on the introduction of isotopes for its discovery. 

Schoenheimer, R. (1942). The Dynamic State of Body Constituents. (Republished 1964). Hafner Publishing, New York. 

Schoenheimer s concept of the dynamic state of body proteins did not remain unchallenged. In 1955, Monod and co-workers studied the origin of amino acids utilized for the synthesis of newly induced j8-galactosidase in growing E. coli [4]. 

Schoenberg R, Zink S, Staubwasser M, von Blanckenburg F (2008) The stable Crisotope inventory of solid Earth reservoirs determined by double-spike MC-ICP-MS. Chem Geol 249 294-306 Schoenheimer R, Rittenberg D (1939) Studies in protein metabolism I, General considerations in the application of isotopes to the study of protein metabolism. The normal abundance of nitrogen isotopes in amino acids, J Biol Chem 127 285-290... 

For many years, I have been interested in the problem of how proteins are degraded in cells. The dynamic state of cellular proteins (Schoenheimer, 1942) and the important roles of protein degradation in the control of cellular enzyme levels (Schimke Doyle, 1970) have been recognized for a long time, but the underlying molecular mechanisms remained unknown. A clue to an unusual mechanism was provided by observations indicating that the... 

An initially surprising conclusion drawn from the studies of Schoenheimer and Rittenberg was that proteins within cells are in a continuous steady state of synthesis and degradation. The initial biosynthesis, the processing, oxidative and hydrolytic degradative reactions of peptides, and further catabolism of amino acids all combine to form a series of metabolic loops as discussed in Chapter 17 and dealt with further in Chapters 12 and 29. Within cells some proteins are degraded much more rapidly than others, an important aspect of metabolic control. This is accomplished with the aid of the ubiquitin system (Box 10-C) and proteasomes (Box 7-A).107 Proteins secreted into extracellular fluids often undergo more rapid turnover than do those that remain within cells. 

Work on the biosynthesis of cholesterol began in earnest after Rudolf Schoenheimer and David Rittenberg, at Columbia University, developed isotopic tracer techniques for the analysis of biochemical pathways. In 1941, Rittenberg and Konrad Bloch were able to show that deuterium-labeled acetate (C2H, COO ) was a precursor of cholesterol in rats and mice. In 1949, James Bonner and Barbarin Arreguin postulated that three acetates could combine to form a single five-carbon unit called isoprene. 

Schoenheimer and Rittenberg first used isotopes as tracers in the study of intermediary metabolism. 

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