Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020639 (hypoproteinemia)
 1,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male weanling rats were fed a 72% rice diet containing no detectable carnitine and limiting in threonine and lysine. Such dietary conditions may simulate protein malnutrition in man. Under these conditions growth impairment, anemia, hypoproteinemia, and fatty liver developed. The study focused principally on the fatty liver syndrome which was corrected to varying extents depending on degrees of supplementation with carnitine, lysine, threonine, and appropriate combinations of these nutrients. Such reduction in fatty liver accumulation was accounted for principally by the lowering of triglycerides, but also in part of total cholesterol levels. All the data, which also included monitoring carnitine uptake by the tissues and measurement of plasma triglycerides, were consistent with the view that fatty liver accumulation occurs in amino acid deficient diets because (a) of an impairment in the synthesis of the lipoprotein complex mandatory for triglyceride secretion from the liver and (b) from a deficiency of carnitine needed for the intramitochondrial transport of fatty acids prerequisite for their oxidation.
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PMID:Dietary lysine and carnitine: relation to growth and fatty livers in rats. 124 84

Citrin, encoded by SLC25A13, is a liver-type mitochondrial aspartate-glutamate carrier (AGC), of which deficiency, in autosomal recessive trait, causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). NICCD patients have jaundice, hypoproteinemia, hypoglycemia, galactosemia, growth retardation, fatty liver and multiple aminoacidemia including citrulline, methionine, threonine and tyrosine. Some of the neonates who have experienced NICCD suffer from severe CTLN2 more than 10 years or several decades later. In CTLN2, neuropsychotic symptoms such as disorientation, aberrant behavior, coma and death are observed. Laboratory findings reveal hyperammonemia, citrullinemia, fatty liver and liver-specific decrease in a urea cycle enzyme, argininosuccinate synthetase (ASS). In some cases, hyperlipidemia, pancreatitis and hepatoma are accompanied with CTLN2. Citrin as a liver-type AGC plays a role in supplying aspartate to the cytosol for urea, protein and nucleotide synthesis by exchanging mitochondrial aspartate for cytosolic glutamate and proton, and transporting cytosolic NADH reducing equivalent to mitochondria as a member of malate aspartate shuttle essential for aerobic glycolysis. AGC is also important for gluconeogenesis from lactate. Although it is difficult to explain pathogenesis of the symptoms such as cholestasis in NICCD and liver-specific decrease of ASS protein in CTLN2 from the functions of the AGC, some are understandable by the loss of citrin functions. Many CTLN2 patients have been treated with a low protein and high carbohydrate diet and glycerol at the hyperammonemic coma. We argue that those treatments may result in fatty liver, hyperlipidemia, hyperammonemia and even death due to loss of the citrin functions. Loss of citrin first cause deficiency of aspartate in the cytosol, which results in an increase in cytosolic NADH/NAD(+) ratio and then activation of fatty acid synthesis pathway to compensate the aberrant ratio. This follows inhibition of fatty acid oxidation. The peculiar fondness for food of CTLN2 patients who like protein and dislike carbohydrate and sweets may be related to their metabolic requirements.
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PMID:Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier. 1619 99

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a kind of inborn errors of metabolism, with the main clinic manifestations of jaundice, hepatomegaly, and abnormal liver function indices. As a mitochondrial solute carrier protein, citrin plays important roles in aerobic glycolysis, gluconeogenesis, urea cycle, and protein and nucleotide syntheses. Therefore citrin deficiency causes various and complicated metabolic disturbances, such as hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoproteinemia, hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed by mutation analysis of SLC25A13, the gene encoding citrin. The baby (male, 6 months old) was referred to the First Affiliated Hospital with the complaint of jaundice of the skin and sclera, which it had suffered from for nearly 6 months. Physical examination showed obvious jaundice and a palpable liver 5 cm below the right subcostal margin. Liver function tests revealed elevated enzymatic activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA, bilirubin (especially conjugated bilirubin), and decreased levels of total protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol, and triglyceride were also increased, and in particular, the serum AFP level reached 319,225.70 microg/L, a extremely elevated value that has rarely been found in practice before. Tandem mass analysis of a dried blood sample revealed increased levels of free fatty acids and tyrosine, methionine, citrulline, and threonine as well. UP-GC-MS analysis of the urine sample showed elevated galactose and galactitol. The baby was thus diagnosed with suspected NICCD based on the findings. It was then treated with oral arginine and multiple vitamins (including fat-soluble vitamins A, D, E, and K), and was fed with lactose-free and medium-chain fatty acids enriched formula instead of breast feeding. After half a month of treatment, the jaundice disappeared, and the laboratory findings, including liver function indices, blood levels of ammonia, lactate and AFP, were returned to normal level. The baby was followed up for 6 months. It developed well, and the abnormal laboratory findings, including MS-MS and UP-GC-MS analysis results, have been corrected, except a slightly elevated lactate level sometimes. SLC25A13 gene mutation analysis for the patient revealed a compound heterozygote of mutation 851del4 and 1638ins23 and therefore NICCD was definitely diagnosed.
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PMID:[A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency]. 1661 6

When blood plasma proteins are depleted by bleeding with return of the washed red blood cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal. Introduction of variables into their standardized life gives insight into the production of plasma protein. Casein retested as the basal protein in the ration may show high yield of plasma protein, equal to 33 per cent of the protein fed. This equals the potency of liver protein (17 to 33 per cent) and approaches the utilization of plasma protein by mouth (40 per cent). Zein has no effect upon plasma protein regeneration but when it is supplemented with cystine, tryptophane, lysine, and glycine, there is a doubling of the liver basal plasma protein production and a retention of the fed protein nitrogen. Threonine does not modify the above reaction. Liver protein supplemented with cystine, leucine, glutamic acid, and glycine in the basal diet yields double the amount of new formed plasma protein compared with liver alone. This combination is then as potent as plasma protein itself when given by mouth-40 per cent utilization. Tyrosine or lysine, arginine, and isoleucine do not modify the above responses. Methionine is not as effective as cystine in supplementing gelatin and tyrosine to produce plasma protein. Cystine, leucine, and glutamic acid appear to be of primary importance in the building of new plasma protein in these experiments. Plasma protein formation is dependent upon materials coming from the body reserve and from the diet. Given an exhaustion of the reserve store there is very little plasma protein produced during a protein fast (3 to 6 gm. per week). A turpentine abscess does not modify this fasting plasma protein reaction. Homologous plasma given by vein will promptly correct experimental hypoproteinemia due to bleeding. It will maintain nitrogen equilibrium and replenish protein stores. Even during hypoproteinemia plasma protein may promptly pass out of the circulation to supply body needs for protein. Perhaps the most significant concept which derives from all these experiments is the fluidity of the body protein (including plasma protein)-a ready give and take between the protein depots-a "dynamic equilibrium" of body protein.
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PMID:BLOOD PLASMA PROTEIN PRODUCTION AND UTILIZATION : THE INFLUENCE OF AMINO ACIDS AND OF STERILE ABSCESSES. 1987 Sep 63

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.
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PMID:TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY. 1987 Dec 82

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 B(2) group. A persistent slight weight loss in the face of a strongly positive nitrogen balance may accompany this deficiency.
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PMID:AMINO ACID MIXTURES EFFECTIVE PARENTERALLY FOR LONG CONTINUED PLASMA PROTEIN PRODUCTION. CASEIN DIGESTS COMPARED. 1987 90

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.H(2)O 2.2, dl-tryptophane 0.3, dl-phenylalanine 2, dl-methionine 1.2, l(+)-histidine.HCl.H(2)O 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.
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PMID:PLASMA PROTEIN PRODUCTION INFLUENCED BY AMINO ACID MIXTURES AND LACK OF ESSENTIAL AMINO ACIDS : A DEFICIENCY STATE RELATED TO UNKNOWN FACTORS. 1987 90

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.
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PMID:PLASMA PROTEIN AND HEMOGLOBIN PRODUCTION : DELETION OF INDIVIDUAL AMINO ACIDS FROM GROWTH MIXTURE OF TEN ESSENTIAL AMINO ACIDS. SIGNIFICANT CHANGES IN URINARY NITROGEN. 1987 12

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.
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PMID:ANEMIA AND HYPOPROTEINEMIA : WEIGHT MAINTENANCE EFFECTED BY FOOD PROTEINS BUT NOT BY MIXTURES OF PURE AMINO ACIDS. 1987 13