Effect of Malnutrition on Activity of Two Enzymes Concerned With Aminoacid Metabolism in Human Liver

Stephen, J. M. L.; Waterlow, J. C.

doi:10.1016/s0140-6736(68)92724-4

Cited by 57 publications

(17 citation statements)

References 7 publications

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“…All these experiments on the activity of liver enzymes were made in rats. In a study on malnourished children, liver samples were obtained by biopsy before and after recovery (Stephen & Waterlow, 1968). In the malnourished state ASS, which was then considered to be the rate-limiting enzyme, was reduced and the activity of the`amino acid activating enzymes', as the amino acyl t-RNA synthetases were then called, was increased, in agreement with earlier ®ndings in rats (Mariani et al 1963).…”

Section: The Biochemical Evidencesupporting

confidence: 71%

The mysteries of nitrogen balance

Waterlow¹

1999

Nutr. Res. Rev.

113

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The ®rst part of this review is concerned with the balance between N input and output as urinary urea. I start with some observations on classical biochemical studies of the operation of the urea cycle. According to Krebs, the cycle is instantaneous and automatic, as a result of the irreversibility of the ®rst enzyme, carbamoyl-phosphate synthetase 1 (EC 6.3.5.5; CPS-I), and it should be able to handle many times the normal input to the cycle. It is now generally agreed that acetyl glutamate is a necessary co-factor for CPS-1, but not a regulator. There is abundant evidence that changes in dietary protein supply induce coordinated changes in the amounts of all ®ve urea-cycle enzymes. How this coordination is achieved, and why it should be necessary in view of the properties of the cycle mentioned above, is unknown. At the physiological level it is not clear how a change in protein intake is translated into a change of urea cycle activity. It is very unlikely that the signal is an alteration in the plasma concentration either of total amino-N or of any single amino acid. The immediate substrates of the urea cycle are NH 3 and aspartate, but there have been no measurements of their concentration in the liver in relation to urea production. Measurements of urea kinetics have shown that in many cases urea production exceeds N intake, and it is only through transfer of some of the urea produced to the colon, where it is hydrolysed to NH 3 , that it is possible to achieve N balance. It is beginning to look as if this process is regulated, possibly through the operation of recently discovered urea transporters in the kidney and colon. The second part of the review deals with the synthesis and breakdown of protein. The evidence on whole-body protein turnover under a variety of conditions strongly suggests that the components of turnover, including amino acid oxidation, are in¯uenced and perhaps regulated by amino acid supply or amino acid concentration, with insulin playing an important but secondary role. Molecular biology has provided a great deal of information about the complex processes of protein synthesis and breakdown, but so far has nothing to say about how they are coordinated so that in the steady state they are equal. A simple hypothesis is proposed to ®ll this gap, based on the self-evident fact that for two processes to be coordinated they must have some factor in common. This common factor is the amino acid pool, which provides the substrates for synthesis and represents the products of breakdown. The review concludes that although the achievement and maintenance of N balance is a fact of life that we tend to take for granted, there are many features of it that are not understood, principally the control of urea production and excretion to match the intake, and the coordination of protein synthesis and breakdown to maintain a relatively constant lean body mass.

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Section: The Biochemical Evidencesupporting

confidence: 71%

The mysteries of nitrogen balance

Waterlow¹

1999

Nutr. Res. Rev.

113

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“…In addition, when omnivorous and herbivorous animals are given diets of varying protein contents the activities of the urea cycle enzymes are positively correlated with the level of protein in the diet of rats (Schimke, 1962(Schimke, , 1963Freedland, 1964;Das & Waterlow, 1974), children (Stephen & Waterlow, 1968), pigs (Rosebrough et al 1983;Chen et al 1999) and sheep (Payne & Morris, 1969;Payne & Laws, 1976, 1978. The increased activity facilitates disposal of the higher N loads from high-protein diets through the synthesis of urea from ammonia.…”

Section: High Protein Requirement and Amino Acid Metabolismmentioning

confidence: 99%

Idiosyncratic nutrient requirements of cats appear to be diet-induced evolutionary adaptations

Morris

2002

NRR

140

147

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Cats have obligatory requirements for dietary nutrients that are not essential for other mammals. The present review relates these idiosyncratic nutritional requirements to activities of enzymes involved in the metabolic pathways of these nutrients. The high protein requirement of cats is a consequence of the lack of regulation of the aminotransferases of dispensable N metabolism and of the urea cycle enzymes. The dietary requirements for taurine and arginine are consequences of low activities of two enzymes in the pathways of synthesis that have a negative multiplicative effect on the rate of synthesis. Cats have obligatory dietary requirements for vitamin D and niacin which are the result of high activities of enzymes that catabolise precursors of these vitamins to other compounds. The dietary requirement for pre-formed vitamin A appears to result from deletion of enzymes required for cleavage and oxidation of carotenoids. The n-3 polyunsaturated fatty acids (PUFA) requirements have not been defined but low activities of desaturase enzymes indicate that cats may have a dietary need for pre-formed PUFA in addition to those needed by other animals to maintain normal plasma concentrations. The nutrient requirements of domestic cats support the thesis that their idiosyncratic requirements arose from evolutionary pressures arising from a rigorous diet of animal tissue. These pressures may have favoured energy conservation through deletion of redundant enzymes and modification of enzyme activities to result in metabolites more suited to the cat's metabolism. However, this retrospective viewpoint allows only recognition of association rather than cause and effect.

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“…In malnourished children, however, urea excretion is low, and considerable amounts of nitrogen derived from ammonia are found in blood proteins where the label persists for a considerable period of time. Alterations in activity of liver enzymes recently reported to occur in malnourished children would help to explain such changes (16 kwashiorkor. It is evident that marasmus is not just calorie deficiency, as has been suggested (22), and the present study provides further justification for retaining the term protein-calorie malnutrition to include kwashiorkor, marasmus, and intermediate forms (23).…”

Section: Discussionmentioning

confidence: 92%