scholarly journals TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY

1943 ◽  
Vol 77 (3) ◽  
pp. 277-295 ◽  
Author(s):  
S. C. Madden ◽  
J. R. Carter ◽  
A. A. Kattus ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Protein Intake ◽  
Protein Production ◽  
The Body ◽  
Acid Mixture ◽  
Negative Nitrogen Balance ◽  
Growth Mixture

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.

scholarly journals HEMOGLOBIN AND PLASMA PROTEIN

1943 ◽  
Vol 77 (4) ◽  
pp. 375-396 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
The Body ◽  
Acid Mixture ◽  
Blood Proteins ◽  
Body Protein ◽  
Growth Mixture ◽  
Amino Acid Mixtures ◽  
Hemoglobin Production

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.

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
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Protein Production ◽  
Daily Intake ◽  
Essential Amino Acids ◽  
Nitrogen Excretion ◽  
Acid Mixture ◽  
Rapid Weight Loss ◽  
Urinary Nitrogen

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.

scholarly journals PLASMA PROTEIN AND HEMOGLOBIN PRODUCTION

1947 ◽  
Vol 85 (3) ◽  
pp. 243-265 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Essential Amino Acids ◽  
Amino Acid Mixture ◽  
Blood Protein ◽  
Acid Mixture ◽  
Amino Acid Mixtures ◽  
Urinary Nitrogen

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.

High Protein Intake during Continuous Hemodiafiltration: Impact on Amino Acids and Nitrogen Balance

2002 ◽  
Vol 25 (4) ◽  
pp. 261-268 ◽  
Author(s):  
R. Bellomo ◽  
H. K. Tan ◽  
S. Bhonagiri ◽  
I. Gopal ◽  
J. Seacombe ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Nitrogen Balance ◽  
Protein Intake ◽  
Protein Supplementation ◽  
High Protein ◽  
Total Serum ◽  
Amino Acid Supplementation ◽  
Continuous Hemodiafiltration ◽  
High Protein Intake

Aims To study the effect of combined continuous veno-venous hemodiafiltration (CVVHDF) and high (2.5 g/kg/day) parenteral amino acid supplementation on nitrogen balance, amino acid losses and azotemic control in a cohort of patients with severe acute renal failure (ARF). Methods We administered 2.5 grams/kg/day of amino acids intravenously to seven critically ill patients with ARF. We obtained paired blood and ultrafiltrate (UF) samples (n=20) and calculated amino acid clearances and losses, nitrogen balance, protein catabolic rate and total nitrogen losses. Results The median total serum amino acid concentration was high at 5.2 mmol/L with particularly high concentrations of ornithine, lysine, and phenylalanine, but a low level of histidine. The median overall amino acid clearance was 18.6 ml/min (range: 12 to 29 ml/min). UF losses as percentage of administered dose were high for tyrosine (53.6 %) but low for methionine (3.0 %) and arginine (2.3 %). A positive nitrogen balance was achieved in 7 (35%) of the 20 study days with an overall median nitrogen balance of -1.8 g/day. Urea levels were maintained at a median of 26.6 mmol/L. Conclusions High protein intake increases the serum concentrations of most amino acids. Such protein supplementation, when coupled with CVVHDF, achieves a slightly negative overall nitrogen balance in extremely catabolic patients while still allowing adequate azotemic control.

scholarly journals Conversion Percentage of Tryptophan to Nicotinamide is Higher in Rice Protein Diet than in Wheat Protein Diet in Rats

2015 ◽  
Vol 8 ◽  
pp. IJTR.S22444
Author(s):  
Katsumi Shibata ◽  
Tsutomu Fukuwatari ◽  
Tomoyo Kawamura
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Body Weight Gain ◽  
Acid Value ◽  
Amino Acid Mixture ◽  
The Body ◽  
Protein Diet ◽  
Acid Mixture ◽  
Wheat Protein ◽  
Rice Protein

We reported previously that the pellagragenic property of corn protein is not only low L-tryptophan concentration but also the lower conversion percentage of L-tryptophan to nicotinamide; the amino acid composition greatly affected the conversion percentage. The amino acid value of wheat protein is lower than that of rice protein. In the present study, we compare the conversion percentages of L-tryptophan to nicotinamide between wheat protein and rice protein diets in growing rats. The body weight gain for 28 days in rats fed with a 10% amino acid mixture diet with wheat protein was lower than that of rats fed with a 10% amino acid diet with rice protein (68.1 ± 1.6 g vs 108.4 ± 1.9 g; P < 0.05). The conversion percentage of L-tryptophan to nicotinamide was also lower for the wheat protein diet compared with the rice protein diet (1.44 ± 0.036% vs 2.84 ± 0.19%; P < 0.05). The addition of limiting amino acids (L-isoleucine, L-lysine, L-tryptophan, L-methionine, L-threonine) to the wheat protein diet improved growth and the conversion percentage. In conclusion, our result supports the thinking that the composition of amino acids affects the conversion ratio of L-tryptophan to nicotinamide.

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
Keyword(s):  
Amino Acids ◽  
Intravenous Injection ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Protein Production ◽  
Nitrogen Retention ◽  
Essential Amino Acids ◽  
Skin Lesions ◽  
Good Utilization ◽  
Rapid Injection

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.

scholarly journals ANEMIA AND HYPOPROTEINEMIA

1947 ◽  
Vol 85 (3) ◽  
pp. 267-275 ◽  
Author(s):  
L. L. Miller ◽  
F. S. Robscheit-Robbins ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Body Weight ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Essential Amino Acids ◽  
The Body ◽  
Liver Protein ◽  
Food Proteins ◽  
Positive Nitrogen Balance ◽  
Maintain Body Weight

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.

scholarly journals PROTEIN METABOLISM AND EXCHANGE AS INFLUENCED BY CONSTRICTION OF THE VENA CAVA

1949 ◽  
Vol 90 (5) ◽  
pp. 447-459 ◽  
Author(s):  
Frank W. McKee ◽  
Robert E. Hyatt ◽  
William G. Wilt ◽  
Garson H. Tishkoff ◽  
George H. Whipple
Keyword(s):  
Amino Acid ◽  
Ascitic Fluid ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Plasma Proteins ◽  
Vena Cava ◽  
Dominant Factor ◽  
Acid Growth ◽  
Negative Nitrogen Balance ◽  
Fluid Production

Further studies of ascitic fluid production and related factors in dogs with constriction of the vena cava above the diaphragm are reported. Whole dog plasma given intravenously to such animals produces a rise in circulating plasma protein to normal levels, but increases the output of ascitic fluid with a loss of protein via the ascites equivalent to 72, 76, and 65 per cent respectively, of the injected protein. Forced ingestion of water in excess of the test animal's normal needs and desires produces no significant changes in the circulating plasma protein level or in ascitic fluid production. Amino acid growth mixtures given intravenously in distilled water cause weight loss, elevation of circulating plasma proteins, a slightly negative nitrogen balance, but no ascitic fluid production. Amino acid growth mixtures given intravenously in normal saline cause depression of the circulating plasma proteins, negative nitrogen balance, and significant ascitic fluid production. Ascitic fluid given intravenously to the test animals causes a marked depression of circulating plasma proteins, a marked increase in ascitic fluid production containing the equivalent of 116 and 98 per cent of the injected protein, and a negative nitrogen balance. Ascitic fluid given orally produces a marked depression of circulating plasma proteins, and a marked increase in ascitic fluid secretion, containing the equivalent of 66, 66, and 54 per cent respectively, of the ingested protein. Sodium chloride is a dominant factor in some of these experiments where abundant ascites production is recorded. Protein levels and intake are important, but take second place to sodium. Ascitic fluids show electrophoretic patterns which are almost identical to the plasma patterns. The A/G ratios are often equal in ascitic fluid and plasma, sometimes even lower in the ascitic fluid. This emphasizes the ease with which globulins pass cell or other membrane barriers in these experiments.

15N enrichments of casein and plasma protein amino acids in cows ingesting 15N-labelled ammonium sulphate

1997 ◽  
Vol 64 (3) ◽  
pp. 367-376
Author(s):  
FLORENCE CASSERON ◽  
GUIDO RYCHEN ◽  
XIMO RUBERT-ALEMAN ◽  
GERARD JEAN MARTIN ◽  
FRANÇOIS LAURENT
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Plasma Proteins ◽  
Venous Blood ◽  
Isotope Ratio Mass Spectrometry ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Liver Protein ◽  
Lactating Cows

The aim of this work was to determine by ion-exchange liquid chromatography and isotope ratio mass spectrometry the specific 15N enrichment of amino acids in casein and plasma proteins in cows receiving three successive daily oral doses (300, 150 and 150 g) of (15NH4)2SO4 (10 atom per cent isotopic enrichment) and to examine the 15N enrichments obtained with regard to nitrogen transport and metabolism in the lactating cow. To investigate the 15N distribution in amino acids in casein and in plasma proteins, samples of 15N-labelled casein and plasma proteins were extracted either from a pool of several milkings (36–96 h after starting to administer the tracer) or from pooled venous blood (removed on the fourth day after the start of administration) from the four lactating cows. 15N enrichments of the proteins studied, expressed as atoms percent excess, were 0·2509 for casein and 0·0577 for plasma protein. Chromatographic fractionation of the amino acid mixture (protein hydrolysates) resulted in nine groups containing between one and four amino acids: Asp, Ser and Thr; Glu; Pro; Gly, Ala, Val and Met; Ileu and Leu; Tyr; Phe; His and Lys; and Arg. High 15N incorporation was demonstrated in all individual or groups of amino acids studied. In both proteins, Glu appeared to be the most enriched amino acid, Phe and Arg the least enriched. Most aliphatic molecules with a single amino group were highly enriched. The much lower (3·5–7·7-fold) enrichments in plasma protein compared with casein suggest considerable intracellular dilution at the site of liver protein synthesis. Finally, the amino acid separation methods are discussed and suggestions for improving them considered.

HYPERGLYCINEMIA WITH KETOACIDOSIS AND LEUKOPENIA

PEDIATRICS ◽  
1967 ◽  
Vol 39 (6) ◽  
pp. 818-828 ◽  
Author(s):  
Juan Rodriguez Soriano ◽  
Leonard S. Taitz ◽  
Laurence Finberg ◽  
Chester M. Edelmann
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Intake ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Glycine Metabolism ◽  
Biochemical Features

Metabolic investigations are reported in a patient with the clinical and biochemical features of "idiopathic hyperglycinemia." During ketoacidosis elevated concentrations in serum of numerous amino acids were noted, especially leucine, isoleucine, valine, glycine, and lysine. Hyperammonemia was found in association with ketoacidosis. Clinical and biochemical amelioration was induced by restriction of protein intake to 1 gm/kg or less. Although exacerbation was produced by increasing the protein intake to 1.5 gm/kg, the patient was able to tolerate as much as 3.0 gm/kg of an amino acid mixture in which leucine, isoleucine, valine, methionine, and threonine were absent. It is postulated that this disease, in contrast to hyperglycinemia caused by a specific disorder in glycine metabolism, represents a generalized defect in utilization of amino acids resulting in excessive deamination of certain amino acids in the muscle, with consequent hyperammonemia and ketoacidosis. The nature of the defect in amino acid metabolism is unknown.

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