An abnormal urinary excretion of sulphated glycosaminoglycans in a patient with GM-2 gangliosidosis (Tay-Sachs disease) is described. Besides the accumulation of GM-2 ganglioside in liver and lack of hexosaminidase A, the patient shows an abnormal urinary excretion of an iduronic acid-rich low molecular weight heparan sulphate. Also, no dermatan sulphate could be detected in the urine, whereas this compound was the main sulphated glycosaminoglycan in the liver of the patient. Heparan sulphate was the main glycosaminoglycan of normal liver. The total amount of sulphated glycosaminoglycans in the urine and liver of the patient did not differ significantly from the amounts found in the liver and urine of normal subjects. Several plasma glycosidases have been assayed and the activities did not differ significantly from the values obtained for the plasma of normal subjects.
Hypertryptophanemia is a rare inherited metabolic disorder probably caused by a blockage in the conversion of tryptophan to kynurenine, resulting in the accumulation of tryptophan and some of its metabolites in plasma and tissues of affected patients. The patients present mild-to-moderate mental retardation with exaggerated affective responses, periodic mood swings, and apparent hypersexual behavior. Creatine kinase plays a key role in energy metabolism of tissues with intermittently high and fluctuating energy requirements, such as nervous tissue. The main objective of the present study was to investigate the effect of acute administration of tryptophan on creatine kinase activity in brain cortex of Wistar rats. We also studied the in vitro effect of this amino acid on creatine kinase activity in the brain cortex of non-treated rats. The results indicated that tryptophan inhibits creatine kinase in vitro and in vivo. We also observed that the in vitro inhibition was fully prevented but not reversed by pre-incubation with reduced glutathione, suggesting that the inhibitory effect of tryptophan on CK activity is possibly mediated by oxidation of essential thiol groups of the enzyme and/or long-lasting adduct formation. Considering the importance of creatine kinase for the maintenance of energy homeostasis in the brain, it is conceivable that an inhibition of this enzyme activity in the brain may be one of the mechanisms by which tryptophan might be neurotoxic.
ENT-ABIETANE DITERPENES FROM Euphorbia phosphorea (EUPHORBIACEAE). Phytochemical study of the roots of Euphorbia phosphorea Mart. (Euphorbiaceae) was carried out through chromatographic techniques, resulting in the isolation of a new ent-abietane diterpene named 11β,12β-dihydroxy-ent-abieta-8(14),13(15)-dien-16,12α-olide (1), and of nine known ent-abietane diterpenes jolkinolide A (2), jolkinolide E (3), euphorin H (4), euphopilolide (5) jolkinolide F (6), ent-12-hydroxy-12[R]-abieta8(14),13(15)-dien-16,12-olide (7), ent-11α-hydroxyabieta-8(14),13(15)-dien-16,12α-olide (8), 17-hydroxyjolkinolide B (9) and caudicifolin (10). The structures of all compounds were established using spectroscopic techniques such as 1D and 2D NMR, and the structure of the compound 1 was established also with MS, IR and ECD. All compounds were submitted to an in silico study through of a predictive model and then submitted to in vitro tests against Mycobacterium tuberculosis and M. smegmatis for evaluation of their antimycobacterial activity. Compounds 5 and 9 showed mycobacterial growth inhibition with MIC values of 62.5 μM against M. tuberculosis and M. smegmatis, respectively.
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