Full Journal - Journal of Cell and Molecular Biology - Haliç Üniversitesi
Full Journal - Journal of Cell and Molecular Biology - Haliç Üniversitesi
Full Journal - Journal of Cell and Molecular Biology - Haliç Üniversitesi
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<strong>Journal</strong> <strong>of</strong> <strong>Cell</strong> <strong>and</strong> <strong>Molecular</strong> <strong>Biology</strong> 1: 57-67, 2002.<br />
Golden Horn University, Printed in Turkey.<br />
Polyamines in living organisms<br />
Mustafa Yatin<br />
Harvard Medical School, Massachusetts General Hospital, Department <strong>of</strong> Radiology, Division <strong>of</strong><br />
Nuclear Medicine, Boston MA, 02114, USA<br />
Received 30 June 2002; Accepted 10 July 2002<br />
Abstract<br />
Natural polyamines, putrescine, spermidine <strong>and</strong> spermine are ubiquitous cell components essential for normal<br />
cellular functions <strong>and</strong> growth. Chemically these compounds are very simple organic aliphatic cations <strong>and</strong> fully<br />
protonated under physiological conditions. There is a strong correlation between proliferation rate <strong>of</strong> the cells <strong>and</strong><br />
their polyamine contents. Adjustments <strong>of</strong> intracellular concentrations <strong>of</strong> polyamines to physiological requirements<br />
are orchestrated by de novo synthesis, polyamine uptake <strong>and</strong> catabolic reactions. De novo synthesis can in principle<br />
be substituted by polyamine uptake from extracellular environment. Over accumulation <strong>of</strong> polyamines is controlled<br />
by release <strong>and</strong> by a feedback regulation system that involves synthesis <strong>of</strong> a protein, antizyme that leads to<br />
degradation <strong>of</strong> ornithine decarboxylase <strong>and</strong> repression <strong>of</strong> polyamine uptake. The development <strong>of</strong> specific<br />
polyamine biosynthesis inhibitors <strong>and</strong> structural analogues <strong>of</strong> polyamines have revealed that maintaining<br />
polyamine levels are a prerequisite for animal cell proliferation to occur. The interruption <strong>of</strong> polyamine<br />
biosynthesis or minimizing the uptake <strong>of</strong> exogenous polyamines via the polyamine transport system <strong>of</strong>fers<br />
meaningful targets for treatment <strong>of</strong> certain hyperproliferative diseases, most notably cancer. The polyamines<br />
influence confusingly large number biological processes, yet despite several decades <strong>of</strong> intensive research work,<br />
their exact functions in living organisms remains obscure. In this review, the current state <strong>of</strong> scientific knowledge<br />
regarding polyamines, their functions <strong>and</strong> their metabolism in mammalian cells is presented.<br />
KKeeyy wwoorrddss:: Polyamine, ODC, AdoMetDC, polyamine analogues, cancer<br />
Canl› organizmalarda poliaminler<br />
Özet<br />
Do¤al poliaminler putresin, spermidin ve spermin hücrenin normal ifllev ve büyümesi için esas olan yayg›n<br />
hücresel bilefliklerdir. Bu bileflikler kimyasal yönden çok basit organik alifatik katyonlard›r ve fizyolojik k<strong>of</strong>lullarda<br />
tamamen protonlanm›fl durumdad›rlar. Hücrenin ço¤alma h›z› ile poliamin içeri¤i aras›nda çok yak›n bir iliflki<br />
vard›r. Poliamin konsantrasyonlar›n›n fizyolojik ihtiyaca göre ayarlanmas› yeni sentez, poliamin al›nmas› ve<br />
katabolik reaksiyonlar aras›ndaki uyumlulu¤a ba¤l›d›r. Yeni sentez prensip olarak hücre d›fl› ortam›ndan poliamin<br />
al›nmas› ile sa¤lan›r. Poliaminlerin fazla birikimi, sal›nmas› ve protein sentezi, ornitin dekarboksilaz y›k›m›na<br />
neden olan antizim ve poliamin al›m›n›n bask›lanmas›n› içeren feedback regulasyon sistemi taraf›ndan kontrol<br />
edilir. Spesifik poliamin biyosentez inhibitörlerinin ve poliaminlerin yap›sal analoglar›n›n geliflimi, hayvan hücre<br />
ço¤almas›n›n meydana gelmesinin poliamin düzeyine ba¤l› oldu¤unu ortaya koymufltur. Poliamin biyosentezinin<br />
kesintiye u¤rat›lmas› veya poliamin tafl›nma sistemi vas›tas› ile d›fl ortamdan poliaminlerin al›nmas›n›n azalt›lmas›,<br />
çok h›zl› hücre ço¤almas›n›n söz konusu oldu¤u belirli hastal›klar›n, en önemlisi kanserin, tedavisinde anlaml›<br />
sonuçlar vermifltir. Poliaminler çok fazla say›daki biyolojik olaylar› etkiler, onlarca y›ld›r yap›lan yo¤un<br />
araflt›rmalara ra¤men, canl› organizmalardaki tam ifllevleri hala aç›k de¤ildir. Bu derlemede poliaminlerle ilgili son<br />
bilimsel veriler, ifllevleri ve memeli hücrelerindeki metabolizmalar› sunulmufltur.<br />
AAnnaahhttaarr ssöözzccüükklleerr:: Poliamin, ODC, AdoMetDC, poliamin analoglar›, kanser<br />
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