Primerjava kinetičnih lastnosti nekaterih encimov v rakastih in zdravih celicah

Škorja, Jure

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Title:	Primerjava kinetičnih lastnosti nekaterih encimov v rakastih in zdravih celicah
Authors:	ID Škorja, Jure (Author) ID Dobovišek, Andrej (Mentor) More about this mentor... ID Hazabent, Marko (Comentor)
Files:	MAG_Skorja_Jure_2019.pdf (1,04 MB) MD5: 4C3B138F456A14D9534F0DDB32B5CD4B PID: 20.500.12556/dkum/3456cb9d-6dd1-4491-8df2-17ba1d8d37e7
Language:	Slovenian
Work type:	Master's thesis/paper
Typology:	2.09 - Master's Thesis
Organization:	FZV - Faculty of Health Sciences
Abstract:	Pod pojmom rakasto obolenje razumemo mnogo različnih tipov bolezni, za katere je značilna preobrazba zdravih celic v rakaste in pomnožitev le-teh. Le-te se vraščajo v okoliška tkiva, jih okvarijo in pogosto tvorijo tudi zasevke. V tem zaključnem delu 2. stopnje smo raziskovali nastanek rakaste celice iz zdrave celice zaradi okvarjenih genov. Preučevali smo, kakšne spremembe se odvijajo v rakasti celici na nivoju celičnega metabolizma. Posebej nas je zanimalo, ali je možno najti encime, ki so pomembni pri teh spremembah, in kako so ti encimi okvarjeni, kakšne so njihove strukturne spremembe in njihove kinetične lastnosti. Omejili smo se na tri encime: fosfofruktokinaza-1 (PFK1), laktat dehidrogenaza (LDH) in ogljikova anhidraza 9 (CAIX). Poiskali smo različne podvrste encimov PFK1, ki so povezane z različnimi vrstami raka, ter preučili razlike v kinetičnih lastnostih teh encimov glede na njihov divji tip. V kinetiki encimov PFK1 smo odkrili občutne razlike med zdravim in rakastim tkivom. Pri encimu LDH smo ugotovili, da so vrednosti določenih kinetičnih parametrov višje v rakasti kot v zdravi celici. Na aktivnost encima LDH vpliva bližina mutiranega gena KRAS. Za encim CAIX smo ugotovili, da je močneje izražen v kar 11 od 16 rakastih tkiv, za katera je v literaturi možno najti podatke. Največje razlike v izraženosti encima CAIX med zdravim in rakastim tkivom so pri raku ledvic. Zaključimo lahko, da je metabolizem v rakasti celici bistveno drugačen kot v zdravi celici. Spremembe na encimih so posledica nastanka onkogenov. Pomemben faktor v nastanku spremenjenega metabolizma v rakastih celicah je pomanjkanje kisika.
Keywords:	CAIX, LDH, PFK1, Warburgov učinek, metabolizem
Place of publishing:	Maribor
Publisher:	[J. Škorja]
Year of publishing:	2019
PID:	20.500.12556/DKUM-74514
UDC:	576.34:577.15(043.2)
COBISS.SI-ID:	2543012
NUK URN:	URN:SI:UM:DK:OL4VHRZW
Publication date in DKUM:	18.11.2019
Views:	1438
Downloads:	141
Metadata:
Categories:	FZV
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Licences

License:	CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:	The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:	29.08.2019

Secondary language

Language:	English
Title:	Comparison of kinetic properties of some enzymes in cancerous and healthy cells
Abstract:	Under the term ''cancerous disease'', we classify numerous of different type of diseases that have a common feature to develop tumors from a modified cells. These tumors are growing into surrounding tissue, damaging it and often metastasize. In this work we study transformations of healthy cells to cancerous cells due to defective genes. We study changes in cancerous cells on the level of cellular metabolism. In particulary, we are interested in changes of kinetic properties of enzymes. Our study is focused on three enzymes: phosphofructokinase-1 (PFK1), lactate dehydrogenase (LDH) and carbonic anhydrase 9 (CAIX). We searched for different subspecies of enzymes PFK1, that are connected with different types of cancers and studied differences in kinetic properties of these anzymes with respect to their wild type. In the kynetics of enzymes PFK1 we discovered significant differences between healthy and cancerous tissue. The enzyme LDH was found to have the values of certain kinetic parameters higher in cancerous than in healthy cells. The activity of enzyme LDH is influeced by the proximity of the mutated gene KRAS. We have discovered that the enzyme CAIX is strongly expressed in 11 out of 16 cancerous tissues, for which data can be found in the literature. Greatest differences in expression of the enzyme CAIX between healthy and cancerous tissue are in kidney cancer. We can conclude that the metabolism in cancerous cell is significantly different than in healthy cell. The changes on enzymes are the result of formation of oncogens. An important factor in the occurence of altered metabolism in cancerous cells is lack of oxygen.
Keywords:	CAIX, LDH, PFK1, Warburg effect, metabolism

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