The cellular role of transglutaminase

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Bungay, P.J., 1984. The cellular role of transglutaminase. PhD, Nottingham Trent University.

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Abstract

Rat pancreatic islets of Langerhans were found to contain a - and thiol-depegdent transglutaminase enzyme. The apparent Km of the enzyme for was found to be approximately 40 M. Primary amines inhibited islet transglutaminase activity with a potency which decreased in the order monodansylcadaverine > ethylamine > methylamine > propylamine.

Primary amine inhibitors of islet transglutaminase activity also inhibited glucose-stimulated insulin release from intact islets with a potency which matched their relative potency as transglutaminase inhibitors. Although at high concentrations methylamine, ethylamine and propylamine displayed non-specific toxic effects, lower concentrations were found which gave rise to inhibition of insulin release in the absence of perturbing non-specific effects. These observations suggest a role for islet transglutaminase in the mechanism of glucose-stimulated insulin release.

Although putrescine was found to be a good substrate of islet transglutaminase (Km= 0.59mM), its effect on glucose-stimulated insulin release was modest by comparison. Whilst uptake studies suggested that this anomaly may be explained by the limited ability of putrescine to enter islet cells, the possible involvement of this polyamine in the mechanism of insulin release could not be discounted as an explanation.

Evidence was obtained which suggested that rapid synthesis of the polyamines putrescine, spermidine and spermine was not required for stimulus-secretion coupling in the pancreatic B-cell. The high concentrations of these compounds in islets implied a possible role as substrates for islet transglutaminase.

Homogenates of islets contained proteins possessing -glutamyl residues available for amine incorporation catalysed by endogenous transglutaminase. Initial studies suggested that the substrate specificity of islet transglutaminase may be limited to a small number of these proteins.

Studies on passaged tumour lines and primary hepatocellular carcinomata suggested that transglutaminase activity was in general lower in these tissues than in normal tissues. A predominantly particulate distribution of transglutaminase activity appeared to be a marker of tumour tissue and may therefore be important in tumour growth.

Item Type:

Thesis

Creators:

Bungay, P.J.

Date:

1984

ISBN:

9781369325805

Identifiers: