ABSTRACT
The variations in serum and brain concentrations of the large neutral amino acids and the simultaneous changes in brain levels of monoamine neurotransmitters have been studied in normal and streptozotocin-diabetic rats after tryptophan loading. An impaired acute accumulation of tryptophan and serotonin in the brain of diabetic rats was observed, concomitantly with a much faster disappearance of the administered tryptophan from the bloodstream in these animals than in controls. Following the tryptophan load, transient differences in the brain levels of catecholamine neurotransmitters became also apparent between the two groups of rats in correlation with differences in the brain uptake and levels of tyrosine. In diabetic animals, the basal brain concentrations of serotonin and dopamine were normal and those of norepinephrine were increased. Since uptake of the precursors tryptophan and tyrosine from the blood is chronically reduced, it is likely that long-term adjustments of neurotransmitter metabolism occur in the diabetic brain.
Subject(s)
Amino Acids/metabolism , Brain/metabolism , Diabetes Mellitus, Experimental/physiopathology , Neurotransmitter Agents/biosynthesis , Tryptophan/pharmacology , Animals , Brain/drug effects , Dopamine/metabolism , Male , Norepinephrine/metabolism , Phenylalanine/analysis , Phenylalanine/blood , Rats , Rats, Inbred Strains , Serotonin/metabolism , Tryptophan/blood , Tyrosine/analysis , Tyrosine/bloodABSTRACT
Eleven unsaturated peptides, containing one or two dehydro-phenylalanyl (dehydro-Phe) residues and a C-terminal L-amino acid have been hydrogenated in the presence of palladium-on-charcoal. Hydrolysis of the saturated peptides thus obtained gave optically active phenylalanine showing the occurrence of asymmetric induction during the hydrogenation. Both mono-unsaturated dipeptides and doubly unsaturated tripeptides with L-Glu, L-Leu and L-Val as chiral end-group afforded L-Phe in 40-50% optical yield. In the case of the tripeptide N-acetyl-(dehydro-Phe)-(dehydro-Tyr)-L-Glu the asymmetric induction was higher (70%) for the unsaturated residue which is farther from the chiral end-group along the peptide chain. The results are discussed on the bases of Prelog rule and the rigid dissymmetric conformation of the dehydropeptides in solution.
