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Biomedical subjects

P M Daniel

Publications and source records attributed to P M Daniel.

At least 55 records · Page 3Linked to original sources
PubMed1977

The exclusion of L-isoleucine or of L-leucine from the brain of the rat, caused by raised levels of L-valine in the circulation, and the manner in which this exclusion can be partially overcome.

The amino acids L-isoleucine, L-leucine and L-valine appear to compete for a shared transport carrier for entry into the brain of the living rat, since high concentrations of L-valine in the plasma reduced the influx both of L-isoleucine and of L-leucine into the brain to 10-15% of the normal. The exclusion of L-isoleucine or of L-leucine from the brain by a raised level of L-valine in the circulation can be partially overcome by simultaneously raising the concentration of L-isoleucine or of L-leucine in the circulation. These results indicate the important role played by a saturable shared carrier-mediated transport system in ensuring that an adequate supply of these amino acids reaches the brain from the circulation during life. The bearing of our findings on two inborn errors of amino acid metabolism, maple-syrup-urine disease and hypervalinaemia, is discussed.

Animals↗
PubMed1977

The influx of isoleucine into the cerebral hemispheres and cerebellum: carrier-mediated transport and diffusion.

The influx of L-isoleucine from the blood into the cerebral hemispheres, and into the cerebellum, of the living rat was studied. When various raised levels of L-isoleucine were maintained in the circulation, influx did not increase in proportion to the raised blood levels, which showed that a carrier-mediated transport was being saturated. It was found that the values for influx could not be explained precisely by Michaelis-Menten kinetics. The divergence of the observed values for influx, from those which were obtained by the application of Michaelis-Menten kinetics, could be explained if part of the influx was due to a small, non-saturable component. This minor component of influx may be due to diffusion or to a second carrier-mediated transport system that is not readily saturated.

Animals↗
PubMed1976

Amino acid precursors of monoamine neurotransmitters and some factors influencing their supply to the brain.

There is evidence that changes in the concentrations of the monoamine neurotransmitters within the brain are associated with changes in mental processes, with disorders of control of movement and with certain neuropsychiatric diseases. These neurotransmitters are synthesized in the brain from aromatic amino acid precursors that have to be obtained from the circulating blood. In this study some factors which alter the rates of entry of four amino acids (the important neurotransmitter precursors L-tyrosine and L-tryptophan, as well as L-phenylalanine and L-histidine) into the brain have been studied and the findings considered in relation to conditions in which the quantities of one or more of the monoamine neurotransmitters formed within the cerebral cells may be either too large or too small. Thus too little neurotransmitter will be formed if competition between amino acids for the carriers transporting them into the cerebral cells causes the exclusion of a large proportion of any of the aromatic amino acid precursors from the brain. ,or example, L-tryptophan is partially excluded from the brain if a raised level of any one of several other amino acids is maintained in the circulation. Of these, L-phenylalanine inhibits the transport of L-tryptophan into the brain most effectively, while aromatic amino acids in general exclude L-tryptophan more effectively than do other neutral amino acids. Over-production of one or more of the monoamine neurotransmitters is likely to occur when there is too much of one of the aromatic amino acid precursors in the brain cells as a result of abnormally high uptake from the blood, or as a result of their release by an excessive breakdown of the protein within these cells. Underproduction of neurotransmitters may occur in certain disease states, such as some aminoacidurias or Parkinsonism. We have listed some conditions associated with altered mental states or motor disability in which over- or under-production of monoamine neurotransmitters may occur and have tried to relate the findings in human disease with our experimental results.

Amino Acids, Essential↗