H CRE BIYOLOJISI I 2008-2009

1. H�CRE BIYOLOJISI I2008-2009 Prof.Dr. Ayseg�l Topal sarikaya Istanbul �niversitesi Molek�ler Biyoloji ve Genetik B�l�m�

2. H�CRELER ve H�CRE ARASTIRMALARI H�crelerin molek�ler biyolojisini anlamak t�m biyolojik bilimlere temel olan aktif bir arastirma alanidir. Insan genomunun diziliminin tamamlanmasiyla h�cre ve molek�ler biyolojideki gelismeler tip uygulamalrinda yeni ufuklar a�mistir. Kanser h�zrelerinin �ogalmasini durdurmayi hedfleyen �zg�n ila�larin gelistirilmesi Diyabet Parkinson Alzheimer Omurga yaralanmalari ve kalp hastaliklarinda hasar g�rm�s dokunun yerini almak �zere k�k h�crelerin kullanilmasi gibi

3. T�m h�creler evrim s�resince korunmus ortak, temel �zelliklere sahiptir. �r: T�m h�creler genetik materyal olarak DNA kullanirlar, plazma zariyla kusatilmislardir ve enerji metabolizmasi i�in ayni basit mekanizmalari kullanirlar G�n�m�z h�creleri �esitli farkli yasam bi�imleri gelistirmislerdir. Bakteri amip gibi ve maya gibi bir�ok canli kendi basina �ogalabilen tek h�creli organizmalardir. Karmasik yapili organizmalar ise farkli h�crelerin belirli g�revleri yerine getirmek �zere �zellestigi ve koordine bir sekilde islev g�ren h�cre topluluklarindan olusur. �r: Insan birbirinden farkli isleve sahip 200�den fazla �esitte h�creye sahiptir. H�CRELER ve H�CRE ARASTIRMALARI

4. Ilk insan h�cre k�lt�r� 1951 yilinda John Hopkins �niversitesinden George Gey tarafindan baslatildi. H�creler malignant t�m�rlerden elde edildi ve vericisinin adindan �Henrietta Lacks� dolayi �HeLa� olarak adlandirildi. G�n�m�zde h�cenin biyolojisini anlamak i�in yapilan t�m �alismalar �in vitro� dedigimiz v�cut disinda �retilen (k�lt�r� yapilan) h�crelerde yapilir.

5. H�creler �ok Karmasik ve Organize Yapilardir Karmasiklik: Kompleks yapi, �ok par�ali ve dogru yerlesimli olusum dogada hataya karsi d�s�k tolerans, par�alar arasinda etkilesim ve daha fazla kontrol olarak a�iklanabilir H�cresel aktiviteler ise olduk�a d�zenli ve y�ksek d�zeyde kontrol altindadir. DNA duplikasyonu sirasinda her 10 milyon nukleotit katiliminda sadece 1 hata olabilmekte ve hata derhal taninarak onarim sistemleri tarafindan d�zeltilmektedir.

11. H�creler bir genetik programa sahiptir Organizmalar genlerinin kodladigi bilgiye g�re olusurlar. Insan genetik programi eger kelimelere d�k�lseydi miyonlarca sayfadan olusan bir metin olusurdu. Bu �ok b�y�k miktardaki bilgi nukleus i�inde yeralan kromozomlar �zerinde paketlenmistir. Genlerin molek�ler yapisi genetik yapinin degismesine izin verir (mutasyon). Mutasyon bireyler arasindaki �esitliligin olusmasina neden olur ve biyolojik evrimin temelidir.

12. H�creler kendilerini �ogaltma yetenegine sahiptir. Herbir organizma kendini �ogaltabilirse h�crelerde bunu yapabilirler Birana h�creden iki yeni yavru h�cre olusmadan �nce genetik materyal iki katina �ikar ve herbir yeni yavru h�cre ana h�cre ile ayni genetik materyali tasir. Genellikle iki yavru h�crenin hacmi de esittir. Bazi durumlarda insan oositi b�l�nme ge�irdikten sonra bir yavru h�cre genetik materyalin yarisini i�erse de sitoplazmanin tamamina yakini tasir.

13. H�creler Enerjiyi Kazanir ve Kullanir Karmesikligin olusumu ve devamliligi s�rekili bir enerji girdisini gerektirir. Isigin enerjisi fotosentetik h�crelerin membranlarinda bulunan isik absorblayan pigmentler tarfindan tutulur. Isik enerjisi fotosentez ile kimyasal enerjiye d�n�st�r�l�r ve nisasta ve sukroz gibi karbonhidratlarda enerji seklinde depolanir. Glukozun par�alanmasiyla olusan enerji ATP�de depolanir. H�cre makromolek�lleri, organelleri par�alayarak ve yeniden olusturarak �ok fazla miktarda enerji harcar. B�ylece h�cre devamliligini saglar degisen kosullara kolaylikla uyum saglar.

14. H�creler �ok �esitli kimyasal reaksiyonu basariyla ger�eklestiriler En basit bakteri h�cresi bile y�zlerce farkli kimyasal tarnsformasyonu ger�eklestirebilir. Bu reaksiyonlarin hizini artirmak i�in �enzimlere� gereksinim duyulur. H�credeki kimyasal reaksiyonlarin toplamina METABOLIZMA denir

15. H�creler Mekanik Aktivitelere Sahiptir Materyaller bir yerden bir yere tasinir. �esitli yapilar yikilir yeniden yapilir, bazilari birlesir veya ayrilir. H�crenin kendisi bir yerden baska bir yere tasinabilir. Bu tip aktiviteler dinamik motor proteinlerindeki sekil degismeleriyle baslayan h�cre i�indeki mekanik degismeleri temel alir.

16. H�creler Uyaranlara Cevap Verebilir Bazi h�creler uyaranlara karsi bildik yolla tepki verir. �r: protistler karsilarina �ikan objelerden ka�ar veya besin maddelerine dogru hareket ederler. �ok h�creli bitkilerde ve hayvanlarda ise h�creler �ok �zg�n bir yolla �evrelerindeki maddelerle iliskiye giren resept�rlerle kaplidir. H�creler hormonlara, b�y�me fakt�rlerine, h�cre disi maddelere ve diger h�crelerin y�zeyindeki maddelere karsi resept�rlere sahiptir. B�ylece h�creler hedef h�creye karsi �zg�n cevap, metabolik aktivitelerini degistirerek spesifik uyarana karsi �zg�n cevap, hareket veya �l�m gibi cevaplar verebilir.

17. H�creler Kendi Reg�lasyonlarini Yapabilir Karmasikligin devami ve d�zeni s�rekli bir reg�lasyon gerektirir. Bu reg�lasyonun bozulmasi �ok �nemli sonu�lara neden olur. �r: DNA�daki hatalarin d�zeltilmesinde onarim mekanizmasinin bozulmasi h�crede mutasyona ve �esitli hastaliklarin ortaya �ikmasina neden olur. H�crelerin kendi aktivitelerini nasil kontrol ettikleri konusu ise yavas yavas aydinlatilmaya baslamistir

18. Prokaryotik ve �karyotik H�creler temelde iki b�y�k sinifa ayrilir.

24. Similarities between prokaryotes and eukaryotes reflect the fact that eukaryotes almost certainly evolved from prokaryotic ancestors A. Both types of cells encode genetic information in DNA using an identical genetic code B. Both types of cells share a common set of metabolic pathways (glycolysis, TCA cycle) C. Both types of cells share common structural features � similarly constructed plasma membrane that serves as selectively permeable barrier & cell walls (same function, different structure) D. Similar mechanisms for transcription & translation of genetic information, including similar ribosomes E. Similar apparatus for conservation of chemical energy as ATP (located in plasma membrane of prokaryotes & mitochondrial membrane of eukaryotes) F. Similar mechanism of photosynthesis (between cyanobacteria & green plants) G. Similar mechanism for synthesizing & inserting membrane proteins H. Proteasomes (protein digesting structures) of similar construction (between archaeabacteria & eukaryotes)

25. Characteristics that distinguish prokaryotic & eukaryotic cells - eukaryotic cells are much more complex internally (structurally and functionally) than prokaryotes A. Eukaryotes have membrane-bound nucleus with nuclear envelope containing complex pore structures & other organelles; divides eukaryotic cells into nucleus & cytoplasm 1. Prokaryotes have nucleoid (poorly demarcated cell region that lacks boundary membrane separating it from surrounding cytoplasm) & no membrane-bound organelles 2. Despite importance often placed on nucleus as primary criterion for distinguishing prokaryotes & eukaryotes, a group of prokaryotes is reported to have membrane surrounding their genetic material 3. This provides good example of difficulty in making sweeping generalizations that apply to all groups of living organisms

26. B. Prokaryotes � contain relatively small amounts of DNA (~600,000 base pairs [bp] to nearly 8 million bp; ~0.225 � 3 mm); 8 million bp equals DNA molecule nearly 3 mm long 1. Encodes between ~500 to several thousand proteins (1 mm of DNA = ~3 x 106 base pairs) 2. Simplest eukaryotes (4.6 mm or 12 million bp in yeast encoding ~6200 proteins) have slightly more DNA than prokaryotes; most eukaryotes have order of magnitude more DNA (genetic info) C. Eukaryotic chromosomes numerous; unlike prokaryotes, they contain linear DNA tightly associated with proteins to form a complex nucleoprotein material known as chromatin 1. Eukaryotic chromosomes are capable of compacting into mitotic structures

27. D. Eukaryotes contain an array of complex membranous & membrane-bound organelles that divide cytoplasm into compartments within which specialized activities take place; some examples follow: 1. Mitochondria (plants & animals) � make chemical energy available to fuel cell activities; specialized cytoplasmic organelle for doing aerobic respiration 2. Endoplasmic reticulum (plants & animals) � where many cell lipids & proteins are manufactured 3. Golgi complexes (plants & animals) � sorts, modifies, transports materials to specific cell locations 4. Variety of simple membrane-bound vesicles of varying dimensions (plants & animals) 5. Chloroplasts (plants) � specialized cytoplasmic organelle that is the site of photosynthesis 6. Single large vacuole (plants) � occupies most of cell volume 7. Lysosomes � contains hydrolytic enzymes & carries out hydrolytic gestation; endosomes � vesicles bringing materials into cell to often be digested by lysosomes 8. Peroxisomes & glyoxysomes

28. E. Eukaryotes have many such membrane-bound structures; prokaryotes mostly devoid of them (except for infolded bacterial mesosomes & cyanobacteria photosynthetic membranes) 1. Intracytoplasmic communication smaller issue in prokaryotes due to size (simple diffusion works); in eukaryotes, interconnected channels/vesicles transport stuff around cell & outside of cell 2. Eukaryotes have cytoskeletal elements usually lacking in prokaryotes that give cell contractility, movement, support; primitive cytoskeletal filaments recently found in bacteria a. Prokaryotic cytoskeleton much simpler structurally & functionally than that of eukaryotes 3. Prokaryote ribosomes smaller with fewer components than those of eukaryotes (but they essentially have the same function with similar mechanisms) 4. Both eukaryotes & prokaryotes may be surrounded by rigid, nonliving cell wall that protects, but their chemical composition is very different

29. F. No mitosis or meiosis in prokaryotes (binary fission instead); prokaryotes proliferate faster (double in 20 - 40 minutes; they exchange genetic information via conjugation) 1. In eukaryotes, duplicated chromosomes condense into compact structures; separated by mitotic spindle (elaborate; contains microtubules); allows daughter cells to get equal genetic material 2. In prokaryotes, no chromosome compaction & no spindle; DNA is duplicated & copies are separated by growth of intervening cell membrane 3. Prokaryotes do not reproduce sexually, but in conjugation, DNA is exchanged; the recipient almost never gets whole chromosome from donor; cell soon reverts to single chromosome 4. Prokaryotes are not as efficient as eukaryotes in exchanging DNA with other members of their own species 5. Prokaryotes are, however, more adept than eukaryotes at picking up & incorporating foreign DNA from their environment; this has had considerable impact on microbial evolution

30. G. Eukaryotes have more complex locomotor mechanisms than prokaryotes 1. Prokaryotes have thin, rotating protein filament (flagellum) protruding from the cell; rotations exert pressure against surrounding fluid propelling cell through medium 2. Eukaryotes have more complex flagella with different mechanism (also have cilia, pseudopodia) H. Eukaryotes have complex cytoskeletal system (including microfilaments, intermediate filaments & microtubules) & associated motor proteins; prokaryotes do not have such a system I. Eukaryotic cells are capable of ingesting fluid & particulate material by enclosure within plasma membrane vesicles (endocytosis, phagocytosis) J. Eukaryotes have cellulose-containing cell walls in plants K. Eukaryotes have 2 copies of each gene per cell (diploidy), one from each parent with sexual reproduction requiring meiosis & fertilization, unlike binary fission in prokaryotes L. Eukaryotes possess 3 different RNA synthesizing enzymes (RNA polymerases)

31. IV. Prokaryotes are not inferior - metabolically very sophisticated & highly evolved A. They have remained on Earth for more than 3 billion years B. They live on and in eukaryotic organisms, including humans C. Make almost everything they need, e. g., Escherichia coli can live & prosper in a medium containing only 1 or 2 low MW organic compounds & a few inorganic ions 1. Some bacteria can live on a diet consisting solely of inorganic substances 2. One species has been found in wells >1000 m below Earth's surface; live on basalt rock & molecular hydrogen (H2) made by inorganic reactions D. Even the most versatile cells in human require a variety of organic compounds (vitamins, etc.) & other essential substances that they cannot make on their own