2. Nitrogen balance and amino acid oxidation

The manner in which nitrogen balances vary as a function of protein-N intake in adults is illustrated in the upper panel of Figure 1. Three typical conditions are represented: (A) When common foods are consumed, so that dietary protein is accompanied by carbohydrates and fats to the tune of about 150 kcal/g protein-N (i.e., 17% of dietary energy as protein). When no food is consumed, urinary nitrogen excretion is shown here to be about 10 g/d; this amount varies somewhat, depending in particular on the length of the fasting period. (B) When foods high in carbohydrate, but containing essentially no protein, are consumed in amounts sufficient to cover daily energy needs (i.e., - 1500 kcal/d), nitrogen losses are reduced to some 5 g N/d. This corresponds to the minimal or 'obligatory N loss'. Consumption of increasing amounts of protein in addition to the protein-free foods causes the nitrogen balance to become less negative. With an intake of about 12 g of nitrogen/d, the situation is similar to that where usual foods are consumed in amounts covering daily needs, N balance being achieved with intakes of about 12 g of protein-N/d and about 1800 kcal/d. (C) When only protein is consumed, nitrogen balances are less negative than during total food deprivation, but ingestion of 12 g of protein-N per day is not sufficient to achieve N balance. Nitrogen balance can be approached even while the energy balance remains markedly negative, but substantially higher protein intakes are required. This situation is commonly encountered during a 'protein-sparing modified fast', where, after one week of adaptation, a dose of 1.5 g protein/kg body weight/d is generally sufficient to maintain N balance (LINDNER and BLACKBURN, 1976). In subjects affected by trauma or disease, the three curves are all shifted downward, as these conditions bring about increased protein breakdown to amino acids as well as a more rapid amino acid oxidation (KINNEY and ELWYN, 1983). In protein-depleted individuals, on the other hand, N balances are generally less negative and they become more markedly positive during reconvalescence than in well-fed subjects, so that the three curves shown in the upper panel of Figure 1 are shifted upward in such conditions (WATERLOW, 1987). However, even then, N balances do not rise much above a few grams of protein-N retained per day, regardless of the fact that protein and other nutrients may be consumed (or infused parenterally) in amounts greatly exceeding protein and energy requirements (KINNEY and ELWYN, 1983).

Figure 1. (a) N balances and amino acid oxidation.

Upper panel: Nitrogen balances in adults as a function of protein nitrogen intake: (A) when consuming mixed foods (-), (B) 1500 kcal/d of non-protein energy plus variable amounts of protein (-), or (C) only protein (---).

Figure 1. (b) N balances and amino acid oxidation.

Lower panel: Nitrogen excretion rates as a function of protein-N intakes, as implied by the nitrogen balances shown in the upper panel. (Nitrogen balance is shown by.....)

Restatement of these quite familiar N-balance patterns allows us to examine what they imply about rates of amino acid degradation (lower panel of Figure 1), of which one is generally less well aware. The thin dotted line shows the conditions for which N excretion matches N intake, i.e. when N balance is equal to zero. It can be seen that on high protein and energy intakes, nitrogen excretion increases in direct proportion to further increments in protein intake. On the other hand, amino acid oxidation rates vary substantially when food intake is restricted, as they are then markedly influenced by the availability of other fuels, i.e., glucose, free fatty acids (FFA) and ketone bodies (FLATT and BLACKBURN, 1976). This reflects the fact that maintenance of ATP levels takes priority in all cells, so that any available substrates will be used to regenerate ATP from ADP and phosphate. Consuming carbohydrate to maintain glucose availability reduces the need to obtain energy by amino acid oxidation. Ingestion of some 100 g of carbohydrate per day reduces N excretion by about half, a phenomenon well known as the 'protein-sparing effect of dietary carbohydrate' (GAMBLE, 1946). Unfortunately, influx of exogenous carbohydrates is much less effective in curtailing N losses in the face of disease, even in high doses (KINNEY and ELWYN, 1983). During prolonged starvation, mobilization of endogenous fat reserves can yield enough substrates to meet almost all of the body's energy needs, thanks to the production of ketone bodies by the liver which can be used by the brain instead of glucose (CAHILL, 1970). However, about two weeks of starvation elapse before circulating ketone body levels rise enough for the combined availability of FFA, ß-hydroxy-butyrate and acetoacetate to allow maximal curtailment of amino acid oxidation. Having learned to recognize the importance of energy metabolism on the nitrogen balance, much attention has been focused on the interactions between metabolic fuels, hormone levels and the protein economy (CAHILL, 1971; FLATT and BLACKBURN, 1974). However, the concepts which have evolved and which shape much of our thinking in this area are based primarily on observations made under conditions of protein and/or energy deprivation. They are of little help in explaining the control of amino acid oxidation under conditions of plenty.