A historical perspective
The early history of protein metabolism and nutrition is closely tied to the discovery of nitrogen and its distribution in nature. The reason for this is that pro-teins, on average, contain about 16% nitrogen by weight (to convert nitrogen to protein it is necessary to multiply by 6.25). Daniel Rutherford, in Edinburgh, can be regarded as the discoverer of nitrogen, which he called “phlogisticated air” in his Doctorate in Medicine thesis in 1792.
The first amino acid to be discovered was cystine, which was extracted from a urinary calculus by Wallaston in England in 1810. It was not until 1935 that threonine, the last of the so-called nutritionally indispensable (essential) amino acids for mammals, including man, was discovered by WC Rose at the University of Illinois. Finally, the term “protein” was invented by the Swedish chemist Jons Jakob Berzelius (1779–1848) and this was later accepted and promoted by the influential Dutch chemist Gerhardus Mulder in 1838.
The nutritional importance of nitrogenous com-ponents in the diet was first recognized in 1816 by Magendie. He described experiments in dogs that received only sugar and olive oil until they died within a few weeks. It was concluded that a nitrogen source was an essential component of the diet. Magendie’s insightful views on nitrogen metabolism and nutri-tion were followed by studies carried out by the French scientific school, including Justus von Leibig, who investigated the chemical basis of protein meta-bolism and discovered that urea was an end-product of protein breakdown in the body. Later, Leibig founded a school of biochemical studies in Gissen and later in Munich, Germany, from which Carl Voit emerged as a distinguished scientist and laid the foundations of modern studies of body nitrogen balance. He, in turn, trained many famous scientific celebrities, including Max Rubner, from Germany, who studied the specific dynamic action of proteins and their effects on energy metabolism, and Wilbur Atwater and Graham Lusk, from the USA, who studied food composition, protein requirements, and energy metabolism. Through their work, and that of others, theories of protein metabolism were proposed and challenged, leading to the more or less contemporary view which was established through the seminal work of Rudolf Schoenheimer, conducted at Columbia University, New York, in the mid-1930s and early 1940s. He applied the new tracer tool of stable isotope-enriched compounds, especially amino acids, in the study of dynamic aspects of protein turnover and amino acid metabolism. Stable isotopes (such as 13C, 18O, and 15N) are naturally present in our environ-ment, including the foods we eat, and they are safe to use in human metabolic studies. Using this approach, Schoenheimer established the fundamental biological principle of a continued tissue and organ protein loss and renewal, which forms the basis for the dietary need for protein or supply of amino acids and a utiliz-able form of nitrogen.
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