Because of turnover, protein synthesis and breakdown can each be involved in the regulation of the growth of tissue protein. To investigate the regulation of skeletal-muscle-protein growth we measured rates of protein synthesis and breakdown in growing rats during development on a good diet, during development on a marginally low-protein diet and during rehabilitation on a good diet after a period of severe protein deficiency. Rates of protein synthesis were measured in vivo with a constant intravenous infusion of [14C]tyrosine. The growth rate of muscle protein was measured and the rate of breakdown calculated as breakdown rate=synthesis rate-growth rate. These measurements showed that during development on a good diet there was a fall with age in the rate of protein synthesis resulting from a fall in capacity (RNA concentration) and activity (synthesis rate per unit of RNA). There was a fall with age in the breakdown rate so that the rate was highest in the weaning rats, with a half-life of 3 days. There was a direct correlation between the fractional growth and breakdown rates. During rehabilitation on the good diet, rapid growth was also accompanied by high rates of protein breakdown. During growth on the inadequate diet protein synthesis rates were lesss than in controls, but growth occurred because of decreased rates of protein breakdown. This compression was not complete, however, since ultimate muscle size was only one-half that of controls. It is suggested that increased rates of protein breakdown are a necessary accompaniment to muscle growth and may result from the way in which myofibrils proliferate.

Skeletal-muscle growth and protein turnover.

1. Rats which have been maintained for ten to twelve generations on diets of low protein value were rehabilitated in utero (group P), from birth (group F) and from 4 weeks of age (group W). 2. Group W showed little change in physique, behaviour or learning, indicating that for recovery to be effective refeeding must begin earlier. 3. Group F just failed to attain full physical recovery (90%) whereas group P overgrew by 18.6% in weight and 8.5% in length. 4. In a test designed to evaluate learning ability rehabilitated rats of groups P and F were significantly less successful than normal rats, but more successful than rats of group W or rats of the original undernourished colony. 5. Rehabilitation for a further two generations in groups F and P corrected any residual physical and behavioural defects but produced no further improvement on the Lashley (1938) jumping platform.

/pdf/the-effect-of-rehabilitation-at-different-stages-of-47u714a082.pdf

The effect of rehabilitation at different stages of development of rats marginally malnourished for ten to twelve generations.

1. Measurements were made, at 6 h intervals, of urinary nitrogen output and of the activity of some hepatic enzymes in the rat during adaptation from one level of dietary protein to another. The enzymes measured were arginase (EC 3.5.3.1), argininosuccinate lyase (EC 4.3.2.1), argininosuccinate synthetase (EC 6.3.4.5), glutamate dehydrogenase (EC 1.4.1.2) and alanine and aspartate aminotransferases (EC 2.6.1.2 and EC 2.6.1.1).2. Completeness of urine collection, which was essential for these experiments, was checked by recovery of injected [131I]iodide.3. When the dietary protein content was reduced from 135 to 45 g casein/kg, the urinary N output and the activities of the hepatic enzymes reached their new steady-state levels in 30 h. The reverse adaptation, from 45 to 135 g casein/kg, was also complete in 30 h.4. The rate of change of enzyme activity and the final activity as percentage of initial activity were very similar for all six enzymes, suggesting a common control mechanism. The calculated half-lives of the enzymes were of the order of 7 h, which is very much shorter than those found by previous workers.5. There was no simple relationship between the activity of the urea cycle enzymes and the amount of N excreted. When an equal amount of gelatin was substituted for casein the N output was doubled but there was no change in the activity of the liver enzymes.6. The results suggest that the activity of the urea cycle enzymes depends in part on the amount of N available for excretion after the demands for synthesis have been met. The enzymes, however, appear to be present in excess so that an increased N load was not necessarily accompanied by an increase in enzyme activity.

/pdf/the-rate-of-adaptation-of-urea-cycle-enzymes-2z2uae8oij.pdf

The rate of adaptation of urea cycle enzymes, aminotransferases and glutamic dehydrogenase to changes in dietary protein intake.

Male weanling rats were fed on diets either adequate (55 mg/kg), or severely deficient (0.4 mg/kg) in zinc, either ad lib. or in restricted amounts in four experiments. Measurements were made of growth rates and Zn contents of muscle and several individual tissues. Zn-deficient rats exhibited the expected symptoms of deficiency including growth retardation, cyclic changes in food intake and body-weight. Zn deficiency specifically reduced whole body and muscle growth rates as indicated by the fact that (a) growth rates were lower in ad lib.-fed Zn-deficient rats compared with rats pair-fed on the control diet in two experiments, (b) Zn supplementation increased body-weights of Zn-deficient rats given a restricted amount of diet at a level at which they maintained weight if unsupplemented, (c) Zn supplementation maintained body-weights of Zn-deficient rats fed a restricted amount of diet at a level at which they lost weight if unsupplemented (d) since the ratio, muscle mass: body-weight was lower in the Zn-deficient rats than in the pair-fed control groups, the reduction in muscle mass was greater than the reduction in body-weight. Zn concentrations were maintained in muscle, spleen and thymus, reduced in comparison to some but not all control groups in liver, kidney, testis and intestine, and markedly reduced in plasma and bone. In plasma, Zn concentrations varied inversely with the rate of change of body-weight during the cyclic changes in body-weight. Calculation of the total Zn in the tissues examined showed a marked increase in muscle Zn with a similar loss from bone, indicating that Zn can be redistributed from bone to allow the growth of other tissues. The magnitude of the increase in muscle Zn in the severely Zn-deficient rat, together with the magnitude of the total losses of muscle tissue during the catabolic phases of the cycling, indicate that in the Zn-deficient rat Zn may be highly conserved in catabolic states.

/pdf/growth-and-zinc-homeostasis-in-the-severely-zn-deficient-rat-5c0knny9r7.pdf

Growth and zinc homeostasis in the severely Zn-deficient rat.

1. Colonies of rats have been maintained for twleve generations on diets adequate (dietary protein energy: total metabolizable energy (NDp: E) 0-1) or marginally deficient in protein (NDp: E 0-068). 2. In the malnourished colony, the proportion of "small-for-gestational-age" offspring was ten times as high as amongst the well-nourished colony, growth was slow, sexual maturation delayed, especially in the females, and, when adult, both sexes were significantly lighter and shorter than adults of the well-nourished colony. Organs, other than the eye, weighed less than those of well-nourished "age" controls, but when expressed relative to body-weight, the brain, pituitary, thyroid, adrenals, testes, thymus and eyes were larger, the pancreas unchanged and the kidneys smaller than those of the well-nourished "age" controls. The relative weight of the liver showed little change, being slightly increased in the males and, like the ovaries, slightly reduced in the females. On a body-weight basis, the brains were about 50 percent heavier than normal, but in absolute terms were 5-5-5 percent lighter than those of the well-nourished animals, the cerebellum (10-5 percent lighter in males and 12-9 percent lighter in females) being more severely affected than the cerebrum (4 percent lighter). 3. The young malnourished rats showed increased exploratory activity, transient head tremors and an increased sensitivity to noises, the latter being long-lasting if not permanent. When adult, they showed marked differences in behaviour and learning patterns and it was difficult to attract and hold their attention. In situations demanding a choice the animals were very excited, emitted loud squeals and tried to escape from what was clearly a stressful situation. However, a casual examination of the malnourished adults revealed a rather small, badly groomed, excitable rat without gross abnormalities. 4. The findings are discussed in relation to changes found in malnourished human communities.

/pdf/twelve-generations-of-marginal-protein-deficiency-584hpn4knu.pdf

Twelve generations of marginal protein deficiency.

Cubed diets have been produced with protein values of 6.8 and 10 net dietary protein-calories per cent. Both diets support reproduction over several generations but the colony maintained on the diet of low protein value has low birth weights, slow rates of growth and small adult size. It is suggested that these diets will enable workers to test for possible adaptations in the physical and mental development of rats and dogs over many generations.

P. R. Payne

Papers

Cubed diets of high and low protein values