Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with phenylalanine hydroxylase deficiency show increased concentrations of biopterins and neopterins, and reduced concentrations of serotonin and catecholamines, when phenylalanine concentrations are raised. The pterin rise reflects increased synthesis of dihydroneopterin and tetrahydrobiopterin, and the amine fall a reduction in amine synthesis due to inhibition by phenylalanine of tyrosine and tryptophan transport into neurones. The pterin and amine changes appear to be independent of each other and are present in the central nervous system as well as the periphery; they disappear when phenylalanine concentrations are reduced to normal. Patients with arginase deficiency show a similar amine disturbance but have normal pterin levels. The amine changes probably contribute neurological symptoms but pterin disturbance is not known to affect brain function. Patients with defective biopterin metabolism exhibit severely impaired amine synthesis due to tetrahydrobiopterin deficiency. Pterin concentrations vary with the site of the defect. Symptoms include profound hypokinesis and other features of basal ganglia disease. Neither symptoms nor amine changes are relieved by controlling phenylalanine concentrations. Patients with dihydropteridine reductase (DHPR) deficiency accumulate dihydrobiopterins and develop secondary folate deficiency which resembles that occurring in patients with defective 5,10-methylene tetrahydrofolate reductase activity. The latter disorder is also associated with Parkinsonism and defective amine and pterin turnover in the central nervous system, and a demyelinating illness occurs in both disorders. In DHPR deficiency cerebral calcification may develop in a similar distribution to that seen in congenital folate malabsorption and methotrexate toxicity. Symptoms are ameliorated by therapy with 5-formyltetrahydrofolate but exacerbated by folic acid.
 ...
PMID:Pteridines and mono-amines: relevance to neurological damage. 354 Sep 26

Reduction of dopamine concentrations in the brains of patients with Parkinsonism, together with reported clinical improvement after the administration of dihydroxyphenylalanine, has led to the hypothesis that impaired hydroxylation of tyrosine may be associated with the disease. To test this hypothesis oral loading tests with L-phenylalanine and tyrosine were carried out in patients and controls. After phenylalanine lower blood levels of this were found in Parkinsonian patients than in controls, but tyrosine levels were the same. After tyrosine lower levels of this were also found in patients compared with controls. It is suggested that these findings indicate a decreased rate of tyrosine utilization in Parkinson's disease together with intestinal malabsorption; the latter is supported by the finding of abnormal D-xylose tolerance in these patients.
 ...
PMID:Oral phenylalanine and tyrosine tolerance tests in Parkinsonian patients. 576 91

In order to elucidate the metabolic disorders which were observed for phenylalanine and tyrosine in protein-energy malnutrition, loads of both these amino acids were given to young mothers who showed all the clinical and biochemical symptoms of malnutrition and to healthy controls of the same age. Loads of phenylalanine resulted in higher blood levels, lower blood tyrosine formed from phenylalanine and higher urinary excretion of secondary phenylalanine and tyrosine metabolites in the patients, the former being due to a phenylalanine hydroxylase deficiency, the latter to concomitant disturbances in tyrosine catabolism. Loads of tyrosine resulted in very high urinary excretion of secondary tyrosine metabolites in two patients, due to a p-hydroxyphenylalanine-oxidase deficiency and to a high urinary excretion of tyrosine but almost normal excretion of secondary metabolites in the third patient, which is very likely to be due to a tyrosine-transaminase deficiency. Blood tyrosine levels remained lower in all patients, which may be explained by tyrosine malabsorption and increased utilization by the depleted tissues. Protein-energy malnutrition leads to enzyme deficiencies similar to those observed in some inborn errors of metabolism.
 ...
PMID:Biochemical study of malnutrition. Part V. Metabolism of phenylalanine and tyrosine. 611 98

Before dietary treatment, no significant differences, except for alanine, were found in the amino acid pattern for 22 young mothers and 33 children with protein-energy malnutrition (PEM), the characteristic feature of the serum pattern being the imbalance between essential and non essential amino acids. Apart from lysine, the essential amino acid levels were all below normal. This imbalance may be detected readily from the abnormal values of some particularly sensitive ratios: phenylalanine/tyrosine, valine/glycine, non essential amino acids/essential amino acids and, above all, serine/threonine. A striking finding was the very low threonine levels in all subjects, including local controls and the extremely low tryptophan levels in malnourished children. Before treatment, almost all the erythrocyte amino acid levels as well as the E/S ratios (erythrocytes/serum) were found to be raised in 9 children, demonstrating their poor clinical status. The urinary amino acid level was similar in both, patients before treatment and local controls. The urinary threonine level was low, like in the serum. A normalisation in most of the amino acid levels in the serum was observed upon dietary rehabilitation although not yet significant in all of them. In urine a similar tendency was observed but it was significant for threonine and methionine only, after 2 weeks treatment. Some additional urinary amino acid assays revealed changes upon two weeks dietary rehabilitation that can be interpreted as an increased production of enzymes affected by PEM as well as a growth of the patients' muscular mass. Increased free amino acid losses in the stools, caused by diarrhoea due to secondary malabsorption, and various viral and bacterial infections accompanying malnutrition, illustrate the severity of the diarrhoea.
 ...
PMID:Biochemical study of malnutrition. Part IV. Determination of amino acids in the serum, erythrocytes, urine and stool ultrafiltrates. 678 95

Six patients with gastrointestinal malabsorption and 12 with alcoholic cirrhosis received total parenteral nutrition for 4 wk. Freamine II, the source of the amino acids, is nearly devoid of cystine and tyrosine. We monitored daily nitrogen balance and other nutritional parameters and 22 plasma amino acids. Malabsorbers had a strongly positive nitrogen balance and improvements in nutritional parameters. Plasma amino acids were maintained within or above their normal fasting ranges. Eight of 12 cirrhotics resembled malabsorbing patients in terms of positive nitrogen balance, improved nutritional parameters, and plasma amino acids. In 4 cirrhotics, nitrogen balance remained negative and nutritional repletion failed to occur. Plasma cystine and tyrosine fell to below 30% of their normal fasting means. In 2 of these patients, oral supplements of cystine and tyrosine were given during the fifth week of parenteral nutrition. Plasma cystine and tyrosine were normalized, nitrogen balance became positive, and other repletion indicators demonstrated recovery. We conclude that in 4 cirrhotics, repletion was blocked by deficiencies of cystine and tyrosine, resulting from hepatic inability to synthesize cystine from methionine and tyrosine from phenylalanine.
 ...
PMID:Hypotyrosinemia, hypocystinemia, and failure to retain nitrogen during total parenteral nutrition of cirrhotic patients. 679 45

Blood samples were taken from six overweight women after an overnight fast on three different occasions, before an jejunoileal bypass operation and 1 and 6 months after the operation. The preoperative levels of several plasma free amino acids were significantly elevated, e.g. leucine, isoleucine, valine, lysine, phenylalanine, tyrosine, proline and glutamic acid. One month after the operation all indispensable plasma amino acid concentrations had fallen, in particular the levels of the branched-chain amino acids (BCAA), lysine and tryptophan. Among the dispensable amino acids, plasma tyrosine, arginine and ornithine concentrations were significantly reduced. No further changes of significance were observed in samples taken 5 months later. A close correlation was observed between the plasma levels of retinol-binding protein (RBP) and thyroxine-binding prealbumin (TBPA). One month after the operation the levels of RBP and TBPA had fallen slightly in two subjects and substantially in one subject. A test diet, containing crystalline amino acids, glucose and fat emulsion was given before operation and twice after the operation. Plasma amino acid changes were studied for a period of 2 hours after the meal. The increases in plasma levels following the test meal were lower for many amino acids after the operation. A linear correlation was found between the postprandial increases in BCAA concentrations and the levels of RBP and TBPA. By using complete, carefully defined diets in loading tests, it should be possible to screen for glucose tolerance and amino acid and lipid malabsorption.
 ...
PMID:An oral amino acid loading test before and after intestinal bypass operation for morbid obesity. 713 14

The small intestine's large capacity for glucose absorption and for adaptation seems to contradict the reported importance of carbohydrate malabsorption in short bowel (SB) patients. The aim of the present study was to investigate the occurrence of malabsorption in these patients ingesting realistic amounts of carbohydrates. We performed a dose-response study [ingestion of increasing amounts of glucose and complex carbohydrates (boiled rice and wheat bread), and the nonabsorbable disaccharide lactulose] in SB patients with an intact colon. The hydrogen (H2) -breath test and changes in serum acetate were used to evaluate colonic fermentation and, thus, indirectly, the lack of small intestinal carbohydrate assimilation. Blood glucose and plasma insulin were measured to evaluate absorption. Plasma concentrations of the ileal brake hormones--glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY)--were measured to test whether release of these hormones was related to colonic fermentation. Significant amounts of 25 g and 50 g glucose, and of the bread and rice meals were fermented rather than absorbed, as judged by the increases in end-expiratory H2. Serum acetate concentrations were significantly higher in SB patients than in healthy controls. The orocecal transit times of all test meals ranged from 15 to 120 min. GLP-1 and PYY releases in SB patients were significantly higher than in healthy volunteers. They were mutually parallel and paralleled the increase in insulin. They were not related to ongoing fermentation or to intraluminal carbohydrate content per se, but most probably to absorption of glucose in the distal bowel. In conclusion, well-adapted SB patients had pronounced small intestinal malabsorption of carbohydrate, even after ingestion of small amounts of easily absorbable carbohydrates. A fast small intestinal spreading of carbohydrates, once in the small intestine, and a spill-over to the colon seem to explain the data best.
 ...
PMID:Importance of colonic bacterial fermentation in short bowel patients: small intestinal malabsorption of easily digestible carbohydrate. 1050 35

We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L. kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous for a T-deletion in exon 26, which converts tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an apoB-75.7 carrier, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.
 ...
PMID:Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene. 1159 Feb 10

Peptide YY (PYY) is secreted as a 36 amino acid, straight chain polypeptide, and is found in greatest concentrations in the terminal ileum, colon and rectum. After secretion, dipeptidyl peptidase IV (DPP-IV) cleaves the N-terminal Tyrosine-Proline residues from PYY(1-36), producing PYY(3-36). PYY(1-36) acts at all four human Y receptors, Y1, Y2, Y4 and Y5, while PYY(336) is a specific Y2 receptor agonist. PYY participates in the regulation of appetite and weight balance through hypothalamic-based mechanisms. PYY(1-36) stimulates appetite and weight gain through Y1 and Y5 receptors. PYY(3-36) suppresses appetite and stimulates weight loss through Y2 receptors. GI diseases that cause malabsorption increase both basal and meal-stimulated PYY levels. In contrast, obesity decreases both basal and meal-stimulated PYY levels. Mutations in the human PYY and Y2 receptor genes may contribute to the development of obesity. Small bowel resection elevates PYY levels in humans. Colon resections increase PYY levels in animal models but not in man. PYY changes following bariatric operations are incompletely studied. Vertical banded gastroplasty, open Roux-en-Y gastric bypass and jejunoileal bypass significantly elevate basal and meal-stimulated PYY levels. In dogs with Pavlov pouches, Roux-en-Y duodenojejunostomy (duodenal switch) increases PYY levels compared to Roux-en-Y gastrojejunostomy. DPP-IV activity is increased in obese individuals and remains increased after biliopancreatic diversion. Thus, diseases or operations which cause malabsorption, elevate basal and meal-stimulated PYY levels. Bariatric operations also increase basal and meal-stimulated PYY levels. This suggests that the combination of increased PYY levels and elevated levels of DPP-IV observed after bariatric operations may generate increased circulating levels of PYY(3-36), leading to hypothalamic-mediated suppression of appetite and promotion of weight loss through Y2 receptor mediated mechanisms.
 ...
PMID:Peptide YY(1-36) and peptide YY(3-36): Part II. Changes after gastrointestinal surgery and bariatric surgery. 1675 46

Our objective was to measure maternal plasma and amniotic fluid amino acid concentrations in pregnant women diagnosed as having fetuses with gastroschisis in the second trimester of pregnancy. Twenty-one pregnant women who had fetuses with gastroschisis detected by ultrasonography (gastroschisis group) in the second trimester and 32 women who had abnormal triple screenings indicating an increased risk for Down syndrome but had healthy fetuses (control group) were enrolled in the study. Amniotic fluid was obtained by amniocentesis, and maternal plasma samples were taken simultaneously. The chromosomal analysis of the study and control groups was normal. Levels of free amino acids and non-essential amino acids were measured in plasma and amniotic fluid samples using EZ:fast kits (EZ:fast GC/FID free (physiological) amino acid kit) by gas chromatography (Focus GC AI 3000 Thermo Finnigan analyzer). The mean levels of essential amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) and non-essential amino acids (alanine, glycine, proline, and tyrosine) in amniotic fluid were found to be significantly higher in fetuses with gastroschisis than in the control group (P < 0.05). A significant positive correlation between maternal plasma and amniotic fluid concentrations of essential and nonessential amino acids was found only in the gastroschisis group (P < 0.05). The detection of significantly higher amino acid concentrations in the amniotic fluid of fetuses with a gastroschisis defect than in healthy fetuses suggests the occurrence of amino acid malabsorption or of amino acid leakage from the fetus into amniotic fluid.
 ...
PMID:Elevated amniotic fluid amino acid levels in fetuses with gastroschisis. 1690 76


1 2 Next >>