The development of the concepts of intermediary metabolism of protein and amino acids - that is, the stepwise conversion of these materials to the end products, urea, water, and CO2, with the liberation of energy - has been a continuously evolving process since the early years of the twentieth century. Hopkins in 1913 emphasized that “in the study of the intermediate processes of metabolism we have to deal, not with complex substances which elude ordinary chemical methods, but with simple substances undergoing comprehensible reactions” (Hopkins 1913: 653). Probably the major event in this progression of knowledge was the discovery of the Krebs-Henseleit cycle (Krebs and Henseleit 1932; Cohen 1981).The concept of the “cycle” became fundamental, not only for understanding the excretion of urea but also to the whole future of biochemistry. As Krebs remarked (see Estabrook and Srere 1981) at his 80th birthday symposium:
Perhaps the most novel and fundamental contribution was the discovery of the urea cycle.
It preceded the tricarboxylic cycle for the Nobel Prize. It was very important to have the concept of “the cycle.’’. . .And we know, of course, by now that there are many dozens, if
Not hundreds, of cyclic processes (Estabrook and Srere 1981: xvii).
Dietary proteins are subjected in the body to a series of metabolic reactions, which are outlined in Figure IV. C.3.3. Following ingestion, protein foods undergo digestion, whereupon the amino acids are liberated by the digestive enzymes. Amino acids are then absorbed as free amino acids and as two and three amino acid compounds (di - and tripeptides). Nonabsorbed protein and/or nitrogen compounds appear in the fecal material but may have been subjected to further bacterial reactions in the large intestine. For most protein foods, nitrogen absorption is in excess of 90 percent. Following the distribution of the free amino acids between the extra - and intracellular amino acid pools, subsequent reactions can be considered in four categories:
1. Part of the free amino acid pool is incorporated into tissue proteins. Because of subsequent protein breakdown, these amino acids return to the free pool after a variable length of time and thus become available for reutilization for protein synthesis or for catabolism.
2. Part of the intracellular amino acid pool undergoes catabolic reactions, mainly in the liver. This process leads to loss of the carbon skeleton as CO2 or its deposition as glycogen and fat, whereas the nitrogen is eliminated as urea via the Krebs-Henseleit cycle.
3. Nonessential amino acids are made in the body using amino groups derived from other amino acids (including the EAAs if they are in excess of requirement) and from carbon skeletons formed by reactions common to the intermediary metabolism of carbohydrate (Table rV. C.3.9).
Figure IV. C.3.3. Metabolism of dietary protein. After the absorption of amino acids they are either incorporated into protein or are metabolized into a ketoacids and amino groups. Acetyl coenzyme A may either be used for energy or stored as fat. Pyruvate or Krebs cycle intermediaries may be used for the synthesis of glucose. Additional pathways involve the special role of amino acids for other uses as described in Table IV. C.3.10.
Abbreviations: GDH glutamic dehydrogenase.
AKG alpha ketoglutaric acid OAA oxaloacetic acid THF tetrahydrofolate
Note: Methionine is an essential amino acid but can be synthesized from homocysteine, which, however, is not a normal dietary constituent.
4. Some free amino acids are used for synthesis of a number of new and important N-containing compounds. Examples are shown in Table rVC.3.10 and include purine bases, creatine, gamma amino butyric acid, serotonin, and catecholamines. However, the portion of the total amino acid requirement devoted to this important function is small in absolute terms in comparison with the amount of amino acids needed for protein synthesis.
A summary listing of the end products formed from both the nitrogen and the carbons of the major amino acids as they are degraded is shown in Table rVC.3.11, and a diagrammatic overview of the breakdown of the amino acids for energy and for other purposes is also illustrated in Figure IVC.3.4.
Amino Acid Scoring Systems
Overlapping the development of animal assays for evaluating protein quality were significant advances in organic chemistry that allowed purification and isolation of both proteins and the amino acids. The next major advances in studies of protein metabolism were made by W. C. Rose and his associates at the University of Illinois. Their investigations, which began in the 1920s and extended until the 1950s, were able to distinguish, as unequivocally as is possible in the biological sciences, between the essential (indispensable) and the nonessential (dispensable) amino acids (Rose 1957).
Note: These functions are additional to the roles as constituents of proteins and as energy sources.
The early studies were on rats fed rations containing mixtures of the then-known amino acids in place of protein. The rats did not grow, despite the fact that the concentrations of amino acids were similar to those in milk protein (casein). They did grow, however, when a small amount of intact casein was added. This suggested the presence of an unknown substance in casein, which was later identified as threonine, the last of the essential amino acids in proteins to be recognized.
By the omission of amino acids one at a time, the 10 essential amino acids required by the rat were identified, and their daily needs could be estimated. Similar techniques were subsequently extended to humans, with the help of graduate students who not only isolated or synthesized the amino acids but also served as experimental subjects for nitrogen balance studies.
As human amino acid requirements became known, comparisons were made with the amino acid composition of foods and diets. Subsequently, the capacity of various proteins to meet human protein and amino acid requirements was compared and evaluated, and the results were called protein or amino
Acid scores (Block and Mitchell 1946).The amino acid composition of egg protein was the first reference pattern proposed because it was known to be of high quality in animal-feeding studies. It did not, however, prove to be a suitable pattern, and many proteins scored poorly in relation to egg. This was because the levels of indispensable amino acids contained in egg were well above estimated human needs.
Direct comparison with human amino acid requirements soon followed as these data became available (FAO 1957; FAO/WHO 1973; FAO/WHO/UNU 1985; FAO/WHO 1991). The general expectation developed that not only should the score be able to predict the potential nutritional value of a food (or diet) for humans but that such a score should also correlate directly with the results of animal assays, such as net protein utilization (NPU). This did not always follow, and we now consider that the appropriate standard for dietary assessment for humans should be the human amino acid requirement pattern. Some amino acid scoring patterns recommended for protein evaluation purposes in recent years are shown in Table IVC.3.12.
World History
