scholarly journals PLASMA PROTEIN PRODUCTION INFLUENCED BY AMINO ACID MIXTURES AND LACK OF ESSENTIAL AMINO ACIDS

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.


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.


1996 ◽  
Vol 75 (2) ◽  
pp. 217-235 ◽  
Author(s):  
G. E. Lobley ◽  
A. Connell ◽  
D. K. Revell ◽  
B. J. Bequette ◽  
D. S. Brown ◽  
...  

AbstractThe response in whole-body and splanchnic tissue mass and isotope amino acid transfers in both plasma and blood has been studied in sheep offered 800 g lucerne (Medicago sutiva) pellets/d. Amino acid mass transfers were quantified over a 4 h period,by arterio-venous procedures, across the portal-drained viscera (PDV) and liver on day 5 of an intravenous infusion of either vehicle or the methylated products, choline (0.5 g/d) plus creatine (10 g/d). Isotopic movements were monitored over the same period during a 10 h infusion of a mixture of U-13C-labelled amino acids obtained from hydrolysis of labelled algal cells. Sixteen amino acids were monitored by gas chromatography-mass spectrometry, with thirteen of these analysed within a single chromatographic analysis. Except for methionine, which is discussed in a previous paper, no significant effects of choline plus creatine infusion were observed on any of the variables reported. Whole-body protein irreversible-loss rates ranged from 158 to 245 g/d for the essential amino acids, based on the relative enrichments (dilution of the U-13C molecules by those unlabelled) of free amino acids in arterial plasma, and 206-519 g/d, when blood free amino acid relative enrichments were used for the calculations. Closer agreement was obtained between lysine, threonine, phenylalanine and the branched-chain amino acids. Plasma relative enrichments always exceeded those in blood (P < 0.001), possibly due to hydrolysis of peptides or degradation of protein within the erythrocyte or slow equilibration between plasma and the erythrocyte. Net absorbed amino acids across the PDV were carried predominantly in the plasma. Little evidence was obtained of any major and general involvement of the erythrocytes in the transport of free amino acids from the liver. Net isotope movements also supported these findings. Estimates of protein synthesis rates across the PDV tissues from [U-13C] leucine kinetics showed good agreement with previous values obtained with single-labelled leucine. Variable rates were obtained between the essential amino acids, probably due to different intracellular dilutions. Isotope dilution across the liver was small and could be attributed predominantly to uni-directional transfer from extracellular sources into the hepatocytes and this probably dominates the turnover of the intracellular hepatic amino acid pools.


1978 ◽  
Vol 90 (1) ◽  
pp. 173-183 ◽  
Author(s):  
P. J. Reis ◽  
D. A. Tunks

SUMMARYMerino sheep were given abomasal infusions of either mixtures of amino acids or protein during periods of 8 or 12 days. Effects on wool growth were measured using autoradiography and a clipping procedure which allowed time for the emergence of the wool fibres. Estimates of volume growth rate, from the autoradiographic measurements, and of mass of wool grown, from clipping, were in good agreement.An infusion of a standard mixture of 13 amino acids, which included ten essential amino acids in approximately the proportions in casein, consistently stimulated wool growth. The mean increases in volume and mass of wool grown, during 30 infusions, were 66 and 67% respectively. A mixture of ten essential amino acids alone appeared to be as effective as the standard mixture for stimulating wool growth, and there were no significant differences between the effects on wool growth of casein and the standard mixture of amino acids.The omission of methionine from an infusion of the standard mixture of amino acids, or from a mixture of essential amino acids only, inhibited wool growth rate; both fibre diameter and length of wool grown per day were reduced to below the control values. In addition, the strength of the fibres was considerably reduced.Infusions of zein and of an amino acid mixture simulating the essential amino acid composition of zein both inhibited wool growth rate, due to a reduction in fibre diameter. Similar effects on wool growth were observed when any one of three essential amino acids (lysine, isoleucine or leucine) was omitted from an infusion of the standard mixture of amino acids. The omission of five other essential amino acids (arginine, histidine, phenylalanine, threonine or valine) from the infusion, or variations in the proportions of leucine, lysine or methionine, had no appreciable effects on wool growth.


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.


1985 ◽  
Vol 54 (3) ◽  
pp. 695-703 ◽  
Author(s):  
Chisae Umezawa ◽  
Yuko Maeda ◽  
Kanji Haba ◽  
Mariko Shin ◽  
Keiji Sano

1. To elucidate the causal relation between leucine and the lowering of hepatic NAD content of rats fed on a leucine-excessive diet (Yamada et al. 1979), the effect of leucine on intestinal absorption of tryptophan was investigated.2. Co-administration of [3H]tryptophan and leucine, with leucine at ten times the level of tryptophan, delayed absorption of L-[side chain 2,3-3H]tryptophan from the digestive tract and incorporation of [3H]tryptophan into portal blood, the liver and a protein fraction of the liver. After 120 min, more than 95% of tryptophan was absorbed whether [3H]tryptophan was administered with or without leucine.3. Co-administration of a mixture of ten essential amino acids, in proportions simulating casein, with [3H]tryptophan markedly delayed absorption of tryptophan from the digestive tract. The addition of supplementary leucine to the amino acid mixture, however, caused no further delay.4. In rats prefed a leucine-excessive diet for 1 week [3H]tryptophan was absorbed at the same rate as in rats fed on a control diet.5. The results indicate that competition between tryptophan and leucine for intestinal absorption did not cause lowering of hepatic NAD.


1978 ◽  
Vol 29 (6) ◽  
pp. 1263 ◽  
Author(s):  
AR Egan ◽  
QR Rogers

In a series of 14 experiments young Merino x Dorset Horn or Merino x Suffolk wethers were fed on wheaten straw or wheaten hay supplemented with a mineral mixture and, in some cases, urea and/or molasses. The diets were contrived to provide between 8 and 12% of digestible energy as protein digested in the intestines. A mixture of amino acids estimated to provide suitable proportions of essential amino acids and adequate non-essential amino acids was developed. With each diet, either the complete amino acid mixture, or a mixture from which one essential amino acid was excluded (imbalanced mixture), was infused per abomasum. In several experiments feed intake was depressed by imbalanced mixtures in which methionine, threonine, isoleucine and lysine were the respective deletions from the mixture, but was elevated by the infusion of the complete amino acid mixture. In each experiment an imbalanced infusion resulted in a decrease in plasma concentration of that amino acid excluded from the mixture to levels only 15–50% of control (pre-infusion) levels. All other essential amino acids were increased in concentration in plasma, reaching 1.5 to 6 times the concentrations in pre-infusion conditions. Infusions of greater amounts of amino acids resulted in greater changes in the plasma amino acid concentration. These results indicated that, although ruminant lambs ingesting herbage diets are unlikely to be subjected to an effective amino acid imbalance, they have the physiological capacity to respond to amino acid imbalances. This needs to be considered when rumen bypass of amino acids or proteins is being considered in practical or experimental circumstances.


1943 ◽  
Vol 77 (4) ◽  
pp. 375-396 ◽  
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 due to bleeding, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein. The reserve stores of blood protein producing materials in this way are very largely 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 considerable periods of time. These dogs are very susceptible to infection and to injury by many poisons. Under such conditions, these anemic and hypoproteinemic dogs will use very efficiently a variety of digests (serum, hemoglobin, and casein) and the growth mixture (Rose) of pure amino acids. Nitrogen balance is maintained and considerable new blood proteins are produced. Dog plasma by vein is used freely in these doubly depleted dogs to make new hemoglobin in abundance (Table 1). Serum digests by vein are well utilized to make new hemoglobin and plasma protein in the same dogs (Table 1). Serum digests by mouth are effectively used to make new blood proteins (Table 5). Dog or sheep hemoglobin given in large amounts intraperitoneally are remarkably well utilized to form hemoglobin and plasma protein (Table 6). It must be obvious that the globin of the hemoglobin is saved in these protein-depleted dogs and used to make large amounts of hemoglobin and plasma protein. Hemoglobin digests are also well utilized whether given by mouth (Table 7) or by vein (Table 8) and liberal amounts of plasma protein are manufactured from digests presumably ideally suited for hemoglobin production. Casein digests are well used (Table 8) and form as much new plasma protein as any material tested—even serum digests. Amino acid mixtures are of especial interest. The growth mixture of 10 amino acids (Rose) is well utilized by mouth or by vein and favors new hemoglobin production more than any material tested (Table 2). Cystine replacing methionine in the amino acid mixture increases the plasma protein—hemoglobin output ratio, that is it favors plasma protein production. Digests of various sorts and amino acid mixtures or combinations of digests and amino acid mixtures can be used rapidly and effectively to build new hemoglobin or plasma protein, to maintain nitrogen equilibrium, and to replete reserve protein stores. These experiments point to clinical problems. The unexplained preference given to hemoglobin production in these hypoproteinemic dogs is observed under all conditions, even when whole plasma or serum digests are given by vein. In general, 2 to 4 gm. of hemoglobin are formed for every gram of plasma protein. This all adds up to a remarkable fluidity in the use of plasma protein or hemoglobin which can contribute directly to the body protein pool from which are evolved, without waste of nitrogen, the needed proteins, whether hemoglobin, plasma protein, or tissue proteins.


1977 ◽  
Vol 28 (5) ◽  
pp. 917 ◽  
Author(s):  
H Dove ◽  
GR Pearce ◽  
DE Tribe

Male crossbred lambs weighing 12.5 kg (period 1), 20 kg (period 2) and 30 kg (period 3) were infused per abomasum with milk-based diets in which crude protein (CP) and energy contents were constant at a given Iiveweight, but in which the proportion of CP supplied as essential amino acids (EAA) varied from 120 to 876 g EAA/kg CP. Responses in liveweight gain, nitrogen balance and metabolizable energy (ME) intake (period 1 only) were measured. A number of lambs died while receiving diets containing very high or very low proportions of EAA. Possible reasons for these deaths are discussed. In all periods liveweight gains were greatest in lambs given the control diet (513 g EAA/kg CP). In period 1 this liveweight gain was close to that expected on the basis of energy intake, but in periods 2 and 3, liveweight gains on the control diets were less than anticipated. Reductions in liveweight gain were greater for diets containing low proportions of EAA than those containing high proportions. The infusion of diets containing low proportions of EAA markedly increased urinary nitrogen excretion. The effect of diets containing high proportions was less pronounced. As a result of these effects, lambs given the control diet had the highest daily nitrogen balance in all periods. Nitrogen balance was less severely affected by the dietary changes than liveweight gain, particularly with 30 kg lambs. It is suggested that the reduced retention of apparently digested nitrogen in diets other than the control diets reflected the unsuitability of the pattern of absorbed amino acids for protein synthesis. The effect of diet on the components of energy balance in period 1 was less pronounced than its effect on nitrogen balance. The metabolizability of apparently digested energy was lower in diets other than the control diet, especially those containing low proportions of EAA. This is attributed to the energy cost of increased urinary nitrogen excretion on such diets. Alternative interpretations of the results are discussed, and it is suggested that dietary amino acids will be utilized most efficiently for protein synthesis by the tissues of the lamb when essential and non-essential amino acids are provided in approximately equal proportions. There was no conclusive evidence that this optimum proportion was different for older lambs.


1975 ◽  
Vol 228 (5) ◽  
pp. 1606-1614 ◽  
Author(s):  
JK Tews ◽  
NW Colosi ◽  
AE Harper

Within 1.5 h after force-feeding rats one meal of enzymatic hydrolysates of casein, gelatin, lactalbumin, or yeast, alpha-aminoisobutyric acid (AIB) transport in liver slices was stimulated two- to threefold. A complete amino acid mixture also increased AIB transport. Of the 15 amino acids or derivatives tested individually, the dispensable amino acids, especially glycine and alanine, were more stimulatory than the essential amino acids; feeding a mixture of amino acids lacking glycine and alanine increased AIB uptake only slightly. The effects were significantly greater in meal-fed than in ad libitum-fed rats. Increased hepatic concentrations of cyclic AM were usually associated with the increase in AIB transport. Feeding glucose inhibited the increases in transport and cyclic AMP concentration induced by casein hydrolysate or in the stimulation of AIB transport by dietary amino acids. The increases in AIB uptake appeared unrelated to the exchange of endogenous amino acids with medium AIB.


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