Moira A. Elmore

Degradation of thyrotropin-releasing hormone and luteinising hormone-releasing hormone by enzymes of brain tissue.

Abstract: In this article, the enzymes of brain and associated tissues that can degrade thyrotropin‐releasing hormone (TRH) and luteinising hormone‐releasing hormone (LH‐RH) are reviewed. As both TRH and LH‐RH are considered to act as neurotransmitters or neuromodulators in the CNS, attention is paid to the subcellular location of the enzymes described and how their topographies and substrate specificities fit them to playing roles as inactivating agents for TRH and LH‐RH or as regulators of intracellular concentrations of TRH and LH‐RH. Consideration is also given to enzymes involved in biotransformation of TRH to secondary metabolites that exhibit biological activity and to enzymes involved in the metabolism of secondary metabolites.

Further characterization of the substrate specificity of a TRH hydrolysing pyroglutamate aminopeptidase from guinea-pig brain.

In this study the substrate specificity of a pyroglutamate aminopeptidase from synaptosomal membranes of guinea-pig brain was investigated. The enzyme was found to be specific for tripeptides, tripeptide-amides and tetrapeptides which possess the N-terminal sequence Glp-His and as such is specific for Thyrotropin Releasing Hormone or only very closely related peptides. The enzyme was found not to hydrolyse a number of analogues of Thyrotropin Releasing Hormone which have been shown to have therapeutical value in certain neuronal disorders.

Localisation of a particulate luliberin hydrolysing activity in microsomal membranes of guinea pig brain.

A particulate luliberin hydrolysing enzyme has been described for guinea pig brain. Examination of subcellular fractions generated under different conditions indicated that particulate luliberin hydrolysing activity was most closely associated with the microsomal marker, rotenone-insensitive NADH cytochrome C reductase. The results obtained indicate that luliberin hydrolysing activity is not associated with synaptosomal membrane preparations and that such luliberin hydrolysing activity as is observed in synaptosomal membranes is probably the result of contamination by microsomes. The enzyme could be released from microsomes by Triton X-100 treatment and the solubilised enzyme was found to be inhibited by puromycin and sulphydryl reagents but to be unaffected by phosphoramidon, captopril, phenylmethyl sulphonyl fluoride and by chelating agents except 1,10-phenanthroline.