Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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PMID:Pteridines and mono-amines: relevance to neurological damage. 354 Sep 26

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.
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PMID:Biochemical study of malnutrition. Part V. Metabolism of phenylalanine and tyrosine. 611 98