Amino acid and protein metabolism 631 General features

The topic of amino acid and protein metabolism is vast; twenty1 different amino acids can be incorporated into proteins and several others exist in the body, and each has its own pathway for synthesis and degradation (except that the so-called essential amino acids are not synthesised in the human body). Furthermore, the synthesis and degradation of individual proteins (e.g. enzymes under hormonal control) is so specific that it may appear very difficult to make generalisations. The emphasis here will be on aspects that relate to energy metabolism, and on aspects of the control of protein turnover at a whole-body and tissue level where general features of hormone action can be distinguished.

Amino acids can be oxidised just as can glucose and fatty acids. In fact, very little amino acid is lost from the body intact - we shed some in skin cells, and we lose some in faeces and a tiny amount of free amino acid and some protein in the urine. But most of the amino acids we ingest are ultimately oxidised. At a whole-body level, therefore, the total oxidation of amino acids (per day) roughly balances the daily intake of protein, around 70-100 g in the typical Western diet. Amino acid oxidation contributes around 10 -20% of the total oxidative metabolism of the body under normal conditions (Fig. 6.14).

The total content of amino acids in the body (present in proteins) could therefore represent a large store of energy. One important difference between amino acids and carbohydrates and fatty acids, however, is that (in mammals) amino acids are not stored simply for energy production: all proteins have some

Protein 100 g/day

Protein 100 g/day

CO2 plus urea, NH3, equivalent to protein 100 g/day

10 kg protein ? 100 g amino acids Nucleotides, hormones, etc.

CO2 plus urea, NH3, equivalent to protein 100 g/day

300 g/day

10 kg protein ? 100 g amino acids Nucleotides, hormones, etc.

300 g/day

Fig. 6.14 Overview of protein and amino acid turnover in the body. We eat (very approximately) 100 g protein per day and therefore (unless we are growing) must dispose of an equal amount, mainly by oxidation of amino acids with generation of CO2, H2O, urea and some NH3. Of the (approximately) 10 kg of protein in the body, there is continuous synthesis and breakdown of (about) 300 g/day (i.e. a 3% 'turnover'), although this varies greatly from tissue to tissue (Table 6.1). Some of the amino acid pool is used for synthesis of purines, pyrimidines and hormones. This may also be put in terms of nitrogen balance. Each 6.25 g protein contains about 1 g nitrogen. Therefore (in round figures) we take in about 16 g N per day. Each day, around 2 g is lost in faeces, 0.5 g in shed skin cells, etc., and the remainder of the 16 g as urea and NH3 in urine. Reproduced from Frayn (in press).

biological function apart from storage. For this reason, body protein is largely preserved during normal conditions; the amount does not fluctuate like the glycogen store, for instance. However, unlike fatty acids, amino acids can be converted into glucose. This gives the body's protein store a special role during starvation, when the body must maintain the availability of circulating glucose despite the absence of an external carbohydrate supply. (The utilisation of protein in starvation will be considered further in Chapter 8.)

Protein is a constituent of all tissues, but some tissues play a more important role than others in amino acid metabolism. Skeletal muscle, in particular, is important mainly because of its bulk - about 40% of body weight. The liver is important for a number of reasons: because it is the first organ through which amino acids pass after absorption from the intestine; because some important links between amino acid and carbohydrate metabolism occur there; and because it is the organ where urea synthesis takes place.

Both protein and the pools of individual amino acids turn over in a constant cycle of breakdown or utilisation, and replenishment. The rate of protein turnover varies from tissue to tissue. It is normally measured in terms of percentage replacement per day. These estimations are made by studying the incorporation of isotopically labelled amino acids into protein. Usually they measure turnover of mixed proteins. More specific measurements of the turnover of individual proteins can be made (for instance, by isolating them with immuno-logical techniques after incorporation of an isotopically labelled amino acid), and of course the turnover of some individual proteins is controlled on a very specific basis. We can generalise, however, about rates of protein turnover in different tissues (Table 6.1). The percentage replacement rates are very high in liver and the intestine, but muscle, despite a low fractional protein turnover,

Table 6.1 Protein turnover in the whole body and in various tissues.

Organ

% Replacement

Total protein

% Contribution to

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