Mert GUR, Sema Zeynep YILMAZ, Elhan TAKA

GLUTAMAT/GABA-GLUTAMİN ÇEVRİMİNDE GÖREV ALAN TAŞIYICI PROTEİNLER İÇİN TERMODİNAMİĞİN BİRİNCİ YASA ANALİZİ

Glutamin-glutamat/GABA çevrimi (GGC), nörotransmiter homeostazını sürdürmek için glutamatın nörotransmitter havuzunun yenilenmesini sağlayan bir olaylar dizisidir. GGC'de, glutamat veya GABA molekülleri nöronlardan salınır ve ardından astrositlere alınır. Astrositler, glutamat veya GABA moleküllerini glutamine dönüştürür ve onları sinapsa salar. Glutamin molekülleri, glutamat veya GABA sentezi için bir öncü olarak kullanılmak üzere nöronlar tarafından alınır. Bu moleküllerin, nöronların ve astrositlerin hücre zarları boyunca taşınması, taşıyıcı proteinler tarafından sağlanmaktadır. Söz konusu taşıyıcı proteinler biyomoleküler makinalar olup termodinamik çevrimlerde çalışmakta ve giren enerjinin bir kısmını yararlı işe dönüştürmektedir. Moleküllerin/iyonların elektrokimyasal gradyanı yönündeki taşınımından elde eldilen enerji, protein içerisinde mekanik yararlı işe dönüştürülerek moleküllerin/iyonların elektrokimyasal gradyanlarının tersine taşınımı için kullanılmaktadır. Çalışmamızda enerjinin korunumu yasası uygulanmıştır ve çevrim boyunca sisteme giren enerjinin ne kadarının yararlı işe dönüştürüldüğünü gösteren termodinamik birinci yasa verimlilikleri, GGC’de bulunan EAAT, ASCT2, B0AT2, SA, SN ve GABA taşıyıcıları için hesaplanmıştır. Sinapstaki nörotransmitter konsantrasyonları, sinyal iletimiyle değişmekte ve daha sonra bazal seviyelerine geri dönmektedir. Bu ise taşıyıcıların konsatrasyonlara bağlı olarak değişen birinci yasa verimlilik değerleriyle çalışmalarına sebep olmaktadır. EAAT (glutamat taşınımı için), ASCT2, B0AT2, SA SN, GABA (ileri yönde taşınım) için birinci yasa verimliliklerinin aralıkları sırasıyla %60-85, %46-78, %61-89, %61-89, %55-80 ve %54-76 olarak hesaplanmıştır. Taşıyıcı proteinler için elde edilen verimlilik değerleri, günlük hayatımızda karşılaştığımız makro ölçekli ısı makinalarına nazaran çok yüksektir. Buna ek olarak, EAAT proteinin glutamat taşınımını, maksimum %45 değerinde birinci yasa verimliliğiyle gerçekleşen aspartat taşınımına göre, daha yüksek verimlilikle gerçekleştirdiği belirlenmiştir. Dolayısıyla, farklı substratların aynı taşıyıcı tarafından taşınımının farklı verimliliklerle gerçekleşebileceği ortaya konulmuştur.

Anahtar Kelimeler:

Termodinamik, Birinci Yasa Verimliliği, Biyomoleküler Makinalar, Glutamin–Glutamat/GABA çevrimi, EAAT, GABA, Glutamin, Glutamat, Taşıyıcı, Nörotransmitter ve iyon konsantrasyonları

THE FIRST LAW OF THERMODYNAMICS ANALYSIS OF TRANSPORTERS INVOLVED IN THE GLUTAMATE/GABA-GLUTAMINE CYCLE

The glutamine–glutamate/GABA cycle (GGC) is a sequence of events that provides replenishment of the neurotransmitter pool of glutamate in order to maintain neurotransmitter homeostasis. In the GGC, glutamate or GABA molecules are released from neurons and subsequently taken up into astrocytes. Astrocytes convert glutamate or GABA molecules into glutamine and release them into the synapse. Glutamine molecules are taken up by neurons to be used as a precursor for the synthesis of glutamate or GABA. The transport of these molecules across the membranes of neurons and astrocytes is facilitated by transporter proteins. Each of these transporter proteins is a biomolecular machine; they operate on thermodynamic cycles and convert part of the supplied energy input into useful work output. Energy harnessed from the translocation of molecules/ions down their electrochemical gradient is converted into mechanical useful work translocating molecules/ions against their electrochemical gradient. Conservation of energy principle was applied and thermodynamic first law efficiencies, showing how much of the energy input per cycle is converted into useful work, were evaluated for the thermodynamic cycles of EAAT, ASCT2, B0AT2, SA, SN, and GABA transporters involved in the GGC. Neurotransmitter concentrations in the synapse change upon signal arrival and subsequently return to resting levels, causing transporters to operate under various first law efficiencies. Range of first law efficiencies for EAAT (for glutamate transport), ASCT2, B0AT2, SA SN, GABA (forward mode) were calculated as 60-85%, 46-78%, 61-89%, 61-89%, 55-80%, and 54-76%, respectively. Efficiency values obtained for these transporters are much higher than those of the macro-scaled heat engines we encounter in our daily lives. Furthermore, EAAT showed larger thermodynamic first law efficiency for glutamate transport than aspartate transport, which takes place with a maximum efficiency of 45%. Thus, suggesting the possibility that transport of different substrates by the same transporter may take place with different efficiencies.

Keywords:

Thermodynamics, First Law Efficiency, Biomolecular Machines, Glutamine–Glutamate/GABA Cycle, EAAT, GABA, Glutamine, Glutamate, Transporter, Neurotransmitter and Ion Concentrations.,

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