Brain Damage in the Aminoacidurias

Wiltse, Hobart E.; Menkes, John H.

doi:10.1007/978-1-4615-7172-8_8

Cited by 10 publications

(2 citation statements)

References 157 publications

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“…Changes in the amino-acid pool often lead to brain pathology, but the mechanisms underlying such pathology are not well established. It is clear that brain damage occurs in a number of aminoacidurias (Wiltse and Menkes, 1972); those leading to mental retardation have been well examined, but defects in protein metabolism have only rarely been proven. Similarly, although the damage to brain development caused by undernutrition (Patel, Balazs, and Johnson, 1973) is well shown, specific effects on protein metabolism remain to be established.…”

Section: Measurement Of Alterations Of Protein Turnovermentioning

confidence: 99%

The effect of amino acids on protein metabolism as measured in long‐term experiments in immature brain explants

et al. 1978

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In a study of a system suitable for investigating long-term effects on brain protein metabolism, we measured amino-acid incorpration into isolated immature brain explants incubated under sterile conditions up to ten days. Measurements of changes in total proteins, total DNA, cell number during the experiments, and 14C-thymidine incorporation measurements indicated no significant net growth; new cell formation was below 5% in a 5-day period; therefore, amino-acid incorporation was mainly due to protein turnover. The rate of incorporation in our immature brain preparation was similar to that of the adult brain in vivo: by ten days about one-half of the tissue protein turned over. The label incorporated was released in subsequent incubations with cold amino acids. Such release occurred in all subcellular fractions examined. Incorporation was fairly stable; at temperatures below 30 degrees C it rapidly declined, but it was not affected when phenylalanine or the branched chain amino acids (leucine, isoleucine, valine) were elevated in the incubation medium. Brief exposure to low amino-acid media had no effect; longer exposure resulted in tissue damage. Our model system indicates that overall brain protein turnover is not sensitive to such variations in the level of most amino acids, which may occur under various conditions. Protein metabolism of the nervous system occurs at a high rate. A recent long-term labeling method (Lajtha, Latzkovits, and Toth, 1976) gave a best fit to incorporation curves by assuming two compartments for adult brain proteins, one of which (about 6%) has a half-life of 15 hr and the other (94%) has a half-life of ten days. The disappearance of protein-bound label with time under conditions in which all proteins were previously labeled indicated that most, possibly all, proteins in brain are in a dynamic state (Lajtha and Toth, 1966). Incorporation of amino acids was found in all proteins and structures that have been studied to date; myelin proteins previously thought less active are also metabolized at a significant rate (Sabri, Bone, and Davison, 1974; Lajtha, Toth, Fujimoto, and Agrawal, 1977). We have fairly extensive information available in addition to turnover studies about the mechanisms of protein synthesis in brain (Roberts, 1971); protein breakdown was also studied in some detail (Marks and Lajtha, 1971). In contrast to our knowledge about protein metabolism under physiological equilibrium conditions, our information about alterations during functional demands or pathological conditions is scanty. Although a significant amount of work has been reported, largely because of technical difficulties the results are difficult to interpret unequivocally. The present report represents our effort to address some of the obstacles: to develop a system in which influences on long-term incorporation can be studied...

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Section: Measurement Of Alterations Of Protein Turnovermentioning

confidence: 99%

The effect of amino acids on protein metabolism as measured in long‐term experiments in immature brain explants

et al. 1978

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“…Abnormally high levels of brain phenylalanine may inhibit transport of other amino acids into the brain and their utilization for protein synthesis. Cellular respiration, synthesis of neurotransmitter substances, myelination and replication of neurons may also be affected (1,2,3,4). Among these possibilities, the effect of excess phenylalanine on glucose utilization in the brain may be especially important, because the energy requirement of the brain in situ under normal physiological conditions or during development is met almost entirely by the oxidation of glucose.…”

Section: Introductionmentioning

confidence: 99%

Effect of Excess Phenylalanine on Utilization of Glucose in Rat Brain

Kuroda

Sumitomo

Miyao

1974

Pediatrics International

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Summary This study was undertaken to determine the effect of excess phenylalanine on utilization of glucose in rat brain. 1) Carbon dioxide formation from glucose in the homogenates of fetal and adult brains was progressively inhibited as the concentration of phenylalanine was increased in the reaction mixture. On the other hand, carbon dioxide formation from pyruvate was little affected in either the fetal or adult brain when the reaction mixture was supplemented with 5 mM phenylalanine. These results indicate that the high concentration of phenylalanine does not inhibit the tricarboxylic acid cycle activity, but the glycolytic activity in the rat brain. 2) The lactate and glucose concentrations in rat brain were measured at brief intervals after the production of complete ischemia by decapitation, in order to investigate the inhibitory effect of phenylalanine on the glycolytic activity in rat brain in vivo. Lactate production during 3 minutes after decapitation was not significantly inhibited, when the phenylalanine concentration in rat brain was elevated to 0.8 to 1.0 mM.

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Effects of Amino Acid Imbalance on Amino Acid Utilization, Protein Synthesis and Polyribosome Function in Cerebral Cortex

Roberts

1974

Ciba Foundation Symposium 22 ‐ Aromatic Amino Acids in the Brain

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Brain Damage in the Aminoacidurias

Cited by 10 publications

References 157 publications

The effect of amino acids on protein metabolism as measured in long‐term experiments in immature brain explants

The effect of amino acids on protein metabolism as measured in long‐term experiments in immature brain explants

Effect of Excess Phenylalanine on Utilization of Glucose in Rat Brain

Effects of Amino Acid Imbalance on Amino Acid Utilization, Protein Synthesis and Polyribosome Function in Cerebral Cortex

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