scholarly journals AMINO ACID MIXTURES EFFECTIVE PARENTERALLY FOR LONG CONTINUED PLASMA PROTEIN PRODUCTION. CASEIN DIGESTS COMPARED

1944 ◽  
Vol 79 (6) ◽  
pp. 607-624 ◽  
Author(s):  
S. C. Madden ◽  
R. R. Woods ◽  
F. W. Shull ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. The ten growth essential amino acids of Rose plus glycine will maintain nitrogen balance and produce as much new plasma protein as will good diet proteins. This good utilization is demonstrated over periods of several months when the amino acids are given either orally or parenterally. There is no evidence of toxicity in general nor to unnatural forms of these synthetic amino acids in particular. Given parenterally appropriate mixtures of these amino acids are well tolerated even upon rapid injection. The minimal daily requirements for a 10 kilo dog may be given intravenously in 10 minutes without reaction. Subcutaneously a 10 per cent solution may be given rapidly without reaction. Among various mixtures tested Vt approximates a minimum for a 10 kilo dog. It contains in grams (dl-threonine 0.7, dl-valine 1.5, l-(-) leucine 1.5, dl-isoleucine 1.4, dl-lysine hydrochloride 1.5, l(-) tryptophane 0.4, dl-phenylalanine 1.0, dl-methionine 0.6, l(+)-histidine hydrochloride 0.5, l(+)-arginine hydrochloride 0.5, and glycine 1.0. The presence of glycine improves tolerance to rapid intravenous injection, but excess glycine does not improve utilization of the mixture. Over a long period this mixture appears suboptimal in quantity. Doubled it is more than ample. Of two casein digests tested the one prepared by enzymatic hydrolysis provided good nitrogen retention and fairly good plasma protein production but was much less tolerable upon intravenous injection than certain mixtures of pure amino acids. The other one prepared by acid hydrolysis and tryptophane fortification afforded bare nitrogen equilibrium and produced virtually no plasma protein. Skin lesions observed after 10 to 20 weeks of synthetic diet probably reflect a deficiency of some member or members of the vitamin B2 group. A persistent slight weight loss in the face of a strongly positive nitrogen balance may accompany this deficiency.

1947 ◽  
Vol 85 (3) ◽  
pp. 267-275 ◽  
Author(s):  
L. L. Miller ◽  
F. S. Robscheit-Robbins ◽  
G. H. Whipple

Dogs with sustained anemia and hypoproteinemia due to bleeding and a continuing low protein or protein-free diet with abundant iron are used to test the value of food proteins as contrasted with mixtures of pure amino acids. The stimulus of double depletion (anemia and hypoproteinemia) drives the body to use every source of protein and all protein-building materials with the utmost conservation. Raiding of body tissue protein to produce plasma protein and hemoglobin is a factor when protein-building factors are supplied in small amounts. In this severe test (double depletion) the good food proteins in adequate amounts are able to maintain body weight, a strongly positive nitrogen balance, and produce considerable amounts of new hemoglobin and plasma protein. Casein, lactalbumin, whole egg protein, liver protein are all adequate in amounts of 150 to 250 gm. protein per week. Under comparable conditions mixtures of pure amino acids (essential for growth) do produce large amounts of new hemoglobin and plasma protein and a positive nitrogen balance but do not maintain body weight. The loss of weight is conspicuous even with large amounts of amino acids (200 to 300 gm. protein equivalent per week). Methionine, threonine, and phenylalanine are related to nitrogen conservation in growth mixtures of essential amino acids (Paper I) but when these three are given together they have little influence on the doubly depleted dog (Table 3). Some unidentified substance or compound present in certain proteins but absent in mixtures of the essential amino acids may be responsible for these differences in the response of the doubly depleted dog.


1943 ◽  
Vol 77 (3) ◽  
pp. 277-295 ◽  
Author(s):  
S. C. Madden ◽  
J. R. Carter ◽  
A. A. Kattus ◽  
L. L. Miller ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet protein intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. When the protein intake of such dogs is completely replaced by the growth mixture (Rose) of crystalline amino acids, plasma protein production is excellent, weight and nitrogen balance are maintained. This growth mixture consists of ten amino acids, threonine, valine, leucine, isoleucine, tryptophane, lysine, phenylalanine, methionine, histidine, arginine, and is as effective as most diet proteins in plasma protein production. The above amino acid mixture in aqueous solution may be given by vein with equally good plasma protein production and no apparent clinical disturbance even when given rapidly. Cystine may replace methionine in the above mixture with equally good plasma protein production for 7 to 10 days but at the expense of the body tissues, that is, with weight loss and a negative nitrogen balance. The addition of cystine to the protein-free, otherwise adequate diet may result in the production of considerable new plasma protein during a period as long as 1 week (cystine effect). This reaction may depend upon the amino acid constitution of the preceding diet protein in that it occurred following a liver feeding but did not occur after pancreas feeding. Arginine is required in the diet of the protein depleted dog for fabrication of plasma protein. It is apparently not needed for nitrogen balance for as long as 1 or 2 weeks. The omission of either threonine or valine from the growth mixture is quickly followed by a sharp decline in plasma protein formation and by a negative nitrogen balance. When histidine, arginine, and most of the lysine are omitted from the growth mixture, nitrogen balance and weight may be maintained for as long as 1 week but plasma protein production falls off markedly. The findings indicate that the growth mixture of amino acids should be a valuable addition to transfusion and infusion therapy in disease states associated with deficient nitrogen intake or tissue injury and accelerated nitrogen loss, including shock, burns, and major operative procedures.


1945 ◽  
Vol 82 (2) ◽  
pp. 77-92 ◽  
Author(s):  
S. C. Madden ◽  
F. W. Anderson ◽  
J. C. Donovan ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and intoxication and probably to vitamin deficiency. When the diet nitrogen is provided by certain mixtures of the ten growth essential amino acids plus glycine, given intravenously at a rapid rate, plasma protein production is good. The same mixture absorbed subcutaneously at a slower rate may be slightly better utilized. Fed orally the same mixture is better utilized and associated with a lower urinary nitrogen excretion. An ample amino acid mixture for the daily intake of a 10 kilo dog may contain in grams dl-threonine 1.4, dl-valine 3, dl-leucine 3, dl-isoleucine 2, l(+)-lysine·HCl·H2O 2.2, dl-tryptophane 0.3, dl-phenylalanine 2, dl-methionine 1.2, l(+)-histidine·HCl·H2O 1, l(+)-arginine·HCl 1, and glycine 2. Half this quantity is inadequate and not improved by addition of a mixture of alanine, serine, norleucine, proline, hydroxyproline, and tyrosine totalling 1.4 gm. Aspartic acid appears to induce vomiting when added to a mixture of amino acids. The same response has been reported for glutamic acid (8). Omission from the intake of leucine or of leucine and isoleucine results in negative nitrogen balance and rapid weight loss but plasma protein production may be temporarily maintained. It is possible that leucine may be captured from red blood cell destruction. Tryptophane deficiency causes an abrupt decline in plasma protein production. No decline occurred during 2 weeks of histidine deficiency but the urinary nitrogen increased to negative balance. Plasma protein production may be impaired during conditions of dietary deficiency not related to the protein or amino acid intake. Skin lesions and liver function impairment are described. Unidentified factors present in liver and yeast appear to be involved.


1947 ◽  
Vol 85 (3) ◽  
pp. 243-265 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
L. L. Miller ◽  
G. H. Whipple

Given healthy dogs fed abundant iron and protein-free or low protein diets with sustained anemia and hypoproteinemia, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein. Reserve stores of blood protein-building materials are measurably depleted and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for weeks or months depending upon the intake of food proteins or amino acid mixtures. These dogs are very susceptible to infection and various poisons. Dogs tire of these diets and loss of appetite terminates many experiments. Under these conditions (double depletion) standard growth mixtures of essential amino acids are tested to show the response in blood protein output and urinary nitrogen balance. As a part of each tabulated experiment one of the essential amino acids is deleted from the complete growth mixture to compare such response with that of the whole mixture. Methionine, threonine, phenylalanine, and tryptophane when singly eliminated from the complete amino acid mixture do effect a sharp rise in urinary nitrogen. This loss of urinary nitrogen is corrected when the individual amino acid is replaced in the mixture. Histidine, lysine, and valine have a moderate influence upon urinary nitrogen balance toward nitrogen conservation. Leucine, isoleucine, and arginine have minimal or no effect upon urinary nitrogen balance when these individual amino acids are deleted from the complete growth mixture of amino acids during 3 to 4 week periods. Tryptophane and to a less extent phenylalanine and threonine when returned to the amino acid mixture are associated with a conspicuous preponderance of plasma protein output over the hemoglobin output (Table 4). Arginine, lysine, and histidine when returned to the amino acid mixture are associated with a large preponderance of hemoglobin output. Various amino acid mixtures under these conditions may give a positive urinary nitrogen balance and a liberal output of blood proteins but there is always weight loss, however we may choose to explain this loss. These experiments touch on the complex problems of parenteral nutrition, experimental and clinical.


PEDIATRICS ◽  
1955 ◽  
Vol 16 (5) ◽  
pp. 672-672

If the sole purpose of protein in the diet is to furnish amino acids, the amount needed is that which provides the required quantities of essential amino acids. In these studies the requirement of an essential amino acid is determined by feeding a diet made up of purified amino acids and shown to support normal growth (as evidenced by weight nitrogen retention and plasma protein). The amino acid under study is omitted and then reintroduced in increments until normal growth is resumed; the least amount of the amino acid necessary is considered to be the minimum requirement. Using this technique the minimum requirement for infants between 1 and 6 months of age for threonine was 60 mg./kg./day and for phenylalanine, 90 mg./kg./day. An infant ingesting 200 ml./kg./day of woman's milk would receive approximately 104 mg. of threonine and 106 mg. of phenylalanine/kg./day.


PEDIATRICS ◽  
1990 ◽  
Vol 85 (1) ◽  
pp. 85-91 ◽  
Author(s):  
George G. Graham ◽  
Jorge Lembcke ◽  
Enrique Morales

Earlier studies demonstrated that quality protein maize (QPM), with increased lysine and tryptophan and decreased leucine contents, was more digestible and supported 45% greater nitrogen retention than common maize. Ten recovering malnourished children (ages 13 to 29 months, height-ages 5 to 15 months, weight-ages 3 to 11 months) have now received 90% of their diet energy and 100% of protein and fat from QPM. Energy intake was adjusted to allow them to reach the 50th centile of weight-for-length (according to the National Center for Health Statistics) in 90 days (two completed 60 days only). Growth was compared with that of 10 children receiving modified cow's milk formula (CMF). Energy intakes (QPM 110 ± 15, CMF 106 ± 12, corrected for absorption to 94 and 97 kcal/kg.d), crude energy costs of gain (43 ± 9 and 40 ± 10, corrected to 37 and 37 kcal/g), linear growth (1.23 ± 0.24 and 1.33 ± 0.26 cm/mo), gains in height-age (3.1 ± 0.7 and 3.3 ± 1.2 mo), weight gain (2.6 ± 0.6 and 2.6 ± 0.8 g/kg.d), and final sums of fat folds (24.3 ± 3.5 and 27.2 ± 2.9 mm) were not different. Gains in weight-age were greater (7.5 ± 2.3 vs 5.4 ± 1.6 months, P < .05) and serum albumin decreased (4.10 ± 0.24 to 3.77 ± 0.31 g/dL, P < .01) during QPM feeding. Plasma-free total essential amino acids and ratio of these to total essential amino acids were less after QPM than after CMF diets. Equal growth rates with QPM and CMF diets offer great potential for developing- and developed-country children.


1995 ◽  
Vol 1995 ◽  
pp. 36-36
Author(s):  
R.M. Kay ◽  
P.A. Lee

In the UK, pollution of the water system with nitrate nitrogen leaching from the soil is seen as a major problem and farm animal effluents have been identified as a major source of nitrate pollution. It would, therefore, be beneficial to the livestock producer and to the environment if the nitrogen excretion from animals could be kept to a minimum. To limit the excretion of nitrogen by the pig, it is necessary to supply amino acids in the diet in better agreement with its dietary requirements. This could be achieved either by feeding diets according to the pig's requirements based on age and/or weight (phase feeding) or by improving protein quality. The best protein quality would be that which has the same balance of essential amino acids (EAA) with respect to lysine as that required by the pig, i.e. ideal protein. Diets formulated on the basis of total dietary EAA on an ideal protein basis, using crystalline EAA, could enable lower crude protein (CP) diets to be offered whilst maintaining nitrogen retention (NR). An alternative approach to formulating diets would be to base the formulations on either: 1) currently available, commercial database values for ileal digestible EAA values of ingredients to achieve diets as close to ideal protein as possible but within least cost formulation constraints; or 2) ingredients limited simply to cereals and pulses and supplemented with crystalline EAA to formulate as close to ideal protein as possible. The object of the present experiment was to evaluate diets, formulated on this basis, in terms of nitrogen intake (NI), excretion (NE) and retention (NR) in pigs using balance studies.


Author(s):  
T. C. Wang ◽  
M. F. Fuller

An animal's rate of protein accretion (or nitrogen retention) is determined by the most deficient (or first limiting) amino acid in the diet, in a perfectly balanced (or ideal) protein all essential amino acids and the sum of the non-essential amino acids are equally limiting. If a dietary protein had any amino acids in excess of the ideal pattern, then the removal of any of the excess should not affect nitrogen retention. This principle was used to determine the ideal dietary amino acid pattern for growing pigs.Three nitrogen balance trials were carried out with a total of 64 gilts of weight from 30 to 55 kg. Casein and a mixture of amino acids were used in the semi-purified diets. The animals were given the diets at the rate of 93 g/kg BW0.75/d in three equal meals mixed with 0.3 L water. The feeding times were 08.30, 12.30 and 17.30. All pigs received their experimental diets for 7 days, made up of 3 days preliminary and a 4-day collection, except that the preliminary period before the first collection in the first period was 7 days. Before the first collection bladder catheters were introduced.


Sign in / Sign up

Export Citation Format

Share Document