Study of glycogen phosphorylase in Tetrahymena thermophila and its inhibitors

Postgraduate Thesis uoadl:1320705 567 Read counter

Unit:
Κατεύθυνση Βιοχημεία
Library of the School of Science
Deposit date:
2015-03-31
Year:
2015
Author:
Σπυροπούλου Παναγιώτα
Supervisors info:
Αθανασία Σιαφάκα-Καπάδαη Καθηγήτρια (Επιβλέπουσα), Ισιδώρα Παπασιδέρη Καθηγήτρια, Αθανάσιος Γκιμήσης Αναπληρωτής Καθηγητής
Original Title:
Φωσφορυλάση του Γλυκογόνου της Τetrahymena Τhermophila και Μελέτη της Δράσης Αναστολέων του Ενζύμου
Languages:
Greek
Translated title:
Study of glycogen phosphorylase in Tetrahymena thermophila and its inhibitors
Summary:
Because of its central role in glycogen metabolism, glycogen phosphorylase has
been exploited as an important molecular target for type 2 diabetes therapy.
The continued scientific interest has led to the discovery of a large number of
glycogen phosphorylase inhibitors with anti-diabetic properties. Tetrahymena
thermophila is a widely studied model for cellular and molecular biology, in
which almost all mammalian enzymes of carbohydrate and glycogen metabolism are
present.
The current study aims to investigate the utilization of this model eukaryote
in screening of new potential anti-diabetic compounds by performing in vivo and
in vitro tests before conducting research on mammals and clinical trials. For
this purpose, enzyme assays were performed to test the in vitro inhibitory
potency of MNO6B, G2-ANTHRA and AMX117B in T.thermophila. These are organic
compounds that have been shown to inhibit rabbit muscle glycogen phosphorylase
(RMGPb). In this frame, we also examined the enzyme's catalytic activity in
cell homogenate and all subcellular fractions and conducted in silico studies
to further confirm its presence in the ciliate.
The findings presented here indicate that all three RMGPb inhibitors show good
inhibition in T.thermophila homogenates, implying the presence of glycogen
phosphorylase. As revealed by in silico studies, catalytic and inhibitor site's
critical residues of rabbit muscle glycogen phosphorylase are also found in
T.thermophila enzyme. All results suggest that T.thermophila is a useful model
for the evaluation of potent anti-diabetic agents by using both in vivo and in
vitro assays.
Keywords:
Glycogen phosphorylase, Inhibitors of rabbit muscle glycogen phosphorylase, Enzyme assay, Tetrahymena thermophila, In silico studies
Index:
Yes
Number of index pages:
16-23, 135-136
Contains images:
Yes
Number of references:
97
Number of pages:
145
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