The role of transglutaminase in cellular function

Barnes, RN, 1979. The role of transglutaminase in cellular function. PhD, Nottingham Trent University.

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Abstract

The role of transglutaminase in cellular function R.N. Barnes, 1980 Rat liver transglutaminase was purified (414-fold) and demonstrated to be a calcium- and sulphydryl- dependent, non-zymogenic enzyme with a molecular weight of 70000 ± 5000 and a Km app, for putrescine incorporation into N,N'dimethyl casein, of 5.4 x 10-4M. This is the first literature report of a purification of this enzyme.

The enzyme sub-cellular localisation was demonstrated as a 3:2 distribution between the particulate-free supernatant and particulate (600g nuclear-membranous) fractions respectively. The plasma membrane was closely associated with the enzyme in terms of both locale and source of substrate protein. Actin was also shown to be a specific substrate during tissue slice experiments. The data indicated a role in the covalent incorporation of soluble substrates into, and consolidation of, protein aggregates.

The control of transglutaminase activity was shown to be mediated by a binding mechanism involving the particulate fraction, enzyme activation by a range of agents and the metabolic activity of the cell. Elution experiments demonstrated an enzyme reserve which was capable of translocation between the particulate (600g) and soluble cell fractions. This elution was achieved to varying degrees by the use of buffers involving electrostatic, hydrophobic, apolar and chaotropic interactions. Polyamines in conjunction with calcium completely reversed this finding resulting in loss of soluble enzyme and a reduced enzyme activity.

Studies involving model systems of foetal, hepatomegalic and regenerating liver demonstrate the enzyme to be repressed during proliferative growth. Restoration of full activity occurred during cell differentiation and especially maturation.

Platelet aggregation by various agonists was shown to induce insolubilisation of the transglutaminase activity, which may explain how this cell retains the enzyme during the release reaction.

Investigations of rat sarcomata indicate that transglutaminase may have a function in the metastasis of neoplastic tissues.

Item Type:	Thesis
Creators:	Barnes, R.N.
Date:	1979
ISBN:	9781369325980
Identifiers:	Number Type PQ10290349 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	12 Jul 2021 15:37
Last Modified:	24 Jul 2024 14:50
URI:	https://irep.ntu.ac.uk/id/eprint/43421

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