Deletion studies

It Is logical to expect that dietary deletion of one particular essential amino acid should impair growth to the same extent as the omission of another essential amino acid. However, the results of many studies show distinct differences between individual amino acids. Thus, lysine deprivation in fish, chickens and rats (see D'Mello and Lewis, 1978) is accompanied by relatively modest weight losses, whereas isoleucine or threonine defi-inhibit growth more severely. Median survival times for chicks fed diets devoid of lysine or histidine were 53 and 60 days. Isoleucine or valine deprivation reduced median survival times to 18 and 19 days respectively (Ousterhout, 1960). Chicks fed diets lacking in lysine or histidine were also stronger and more active than those deprived of isoleucine or valine. It has been postulated that certain peptides such as carnosine and proteins such as haemoglobin may serve as sources of histidine and lysine in times of restricted supply. Appreciable reserves of carnosine occur in muscle (Maynard et al., 2001). Nevertheless, mortality will occur if animals are deprived of histidine or lysine for prolonged periods of time. Dietary omission of a single essential amino acid might be expected to induce effects similar to deprivation of all amino acids. The experimental evidence indicates that, for example, chicks deprived of lysine survived for longer and lost less weight than those fed a protein-free diet. Similarly in rats fed a diet devoid of lysine, body water losses were less than in those fed a protein-free diet. However, rats fed diets devoid of threonine, isoleucine or methionine plus cystine lost body water to the same extent as those in the protein-free group (see D'Mello and Lewis, 1978).

Extensive morphological changes have been recorded following the imposition of severe amino acid deficiencies. It has been consistently recorded that during acute amino acid deprivation or deficiency in ad libitum-fed animals, there is a severe inhibition of food intake. Diet selection may also be altered under certain conditions (Hrupka et al., 1997, 1999). The resulting morphological responses (Table 1.5) have been attributed to the combined effects of amino acid deficiency and energy restriction. Attempts have, therefore, been directed at overcoming the marked differences in food intake between deficient and control groups by pair-feeding or by force-feeding. However, D'Mello and

Table 1.5. Morphological effects of amino acid deficiencies3.

(Adapted from D'Mello and Lewis, 1978.)

Ad libitum feeding conditions

Force-feeding conditions

Organ affected

(long-term studies'3)

(short-term studies0)

Liver

Enhanced glycogen levels;

Excess glycogen levels; lipid

hepatocytes in periportal region

accumulation in hepatic cells in

distended by lipid droplets

periportal areas; nucleolar

enlargement

Pancreas

Reduced zymogen granules; lipid

Decreased cytoplasm and zymogen

droplets in acinar cells; mitochondria

granules in acinar cells; nucleolar

swollen and deformed

enlargement; oedema

Thymus

Thymic involution; formation of giant

Decrease of lymphocytes in cortex;

cells; loss of normal architecture;

loss of distinction between cortex

depletion of thymocytes

and medulla

Muscle

Degenerative changes; lack of cross-

No changes

striations in fibres; damaged fibres

swollen, hyalinized and fragmented

Testes

Atrophy of seminiferous tubules and

No data

testicular interstitial cells; inhibition of

spermatogenesis

aAs observed in rats deprived of isoleucine, threonine, lysine or histidine. bDuration: 30 days or more. "Feeding period: 3-8 days.

aAs observed in rats deprived of isoleucine, threonine, lysine or histidine. bDuration: 30 days or more. "Feeding period: 3-8 days.

Lewis (1978) concluded that feeding method was less important than duration of exposure to the deficient diet. Thus, similar morphological effects were observed in long-term deprivation of an amino acid under ad libitum conditions as in short-term force-feeding conditions (Table 1.5). Exposure time appears to be a significant factor in the induction of morphological changes during amino acid deprivation. Although ad libitum feeding over a period of about 8 days of a diet devoid of an essential amino acid elicits no adverse histological changes in animals (D'Mello and Lewis, 1978), extensive aberrations do emerge in long-term investigations lasting 30 days or more. In many instances, these abnormalities reflect those observed in animals force-fed incomplete amino acid diets over a shorter duration (typically 3-8 days). It was noted that morphological abnormalities occur even in animals deprived of lysine or histidine (Table 1.5).

Predictably, extensive biochemical changes also occur during acute amino acid deficiency, irrespective of feeding method (Table 1.6). Under these conditions, muscle protein synthesis is rapidly reduced (Tesseraud et ai, 1996), and amino acids including the one missing from the diet are released into the systemic circulation. These amino acids, together with those derived from intestinal absorption, cause an increase in hepatic protein synthesis. The partition of amino acids, however, depends on the dietary level and intake of carbohydrate. Low carbohydrate intake diminishes or eliminates the changes in hepatic protein synthesis. Thus, the biochemical effects of acute amino acid deficiencies represent the consequence of a complex nutritional imbalance rather than that of a simple deficiency (D'Mello and Lewis, 1978).

Insulin-like growth factor-1 (IGF-1) exerts an important effect on whole-body protein synthesis. This factor is complexed with up to six specific binding proteins, which are believed to modulate the biological activity of IGF-1. The results of Takenaka et ai (2000) indicate that a single essential amino acid deficiency may reduce IGF-1 production in rats without affecting plasma IGF-1 binding protein-1. The molecular action of specific amino acids is likely to be an important area for further research.

Table 1.6. Effects of acute amino acid deficiency on protein metabolism. (Adapted from D'Mello and Lewis, 1978.)

Aspect of protein metabolism

Force-feeding studies

Ad //Mum-feeding studies

Protein content of: Liver Muscle Pancreas Free amino acid levels in: Liver Muscle Blood plasma Protein synthesis in: Liver Heart Blood Muscle Kidney

No change Decrease

Decrease

Decrease

Increase

Increase

Increase Increase Increase Decrease No change

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Increase Increase

Increase [Decrease Marginal decrease

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