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Protein Oksidasyonun Biyokimyasal ve Moleküler Mekanizması

Biochemical and Molecular Mechanism of Protein Oxidation

Journal Name:

  • Karaelmas Fen ve Mühendislik Dergisi

Publication Year:

  • 2013

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Free amino acids and amino acid residues in proteins are highly susceptible to oxidation by various oxygen and nitrogen species (ROS, RNS) or metal ions. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms. We report on biochemical and molecular mechanisms of ROS-mediated oxidation of proteins and free amino acids. Oxidation of proteins can lead to hydroxylation of aromatic groups and aliphatic amino acid side chains, nitration of aromatic amino acid residues, nitrosylation of sulfhydryl groups, sulfoxidation of methionine residues, chlorination of aromatic groups and primary amino groups, and to conversion of some amino acid residues to carbonyl derivatives. Oxidation can lead also to cleavage of the polypeptide chain and to formation of cross-linked protein aggregates. The consequent protein oxidation involves several propagating radicals, notably alkoxyl radicals. Furthermore, functional groups of proteins can react with oxidation products of polyunsaturated fatty acids such as 2-alkenals, 4-hydroxy-2-alkenals, and ketoaldehydes and with carbohydrate derivatives (glycation/glycoxidation) to produce inactive derivatives. There is also a correlation between aging and the accumulation of oxidatively damaged proteins, lipids, and nucleic acids. Oxidatively modified proteins have been shown to increase as a function of age. Factors that decelerate protein oxidation also increase the life span of living organisms. Furthermore, a number of age-related or other diseases such as cancer, diabetes mellitus, atherosclerosis, neurodegenerative, and cardiovascular diseases in vertebrates have been shown to be associated with elevated levels of oxidatively modified proteins. The level of these modified molecules can be quantitated by measurement of the protein carbonyls compounds and other oxidized end products content, which have been shown to increase in a variety of diseases and processes, notably during aging as a result of oxidative stress.
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Abstract (Original Language): 
Serbest amino asitler ve proteinlerdeki amino asit kökleri çeşitli reaktif oksijen ve azot türleri (ROT, RAT) ve metal iyonlarının okside edici etkilerine karşı oldukça hassastırlar. ROT üretimi çevresel faktörlerin etkisi ile olduğu kadar hücresel metabolik aktiviteler sonucunda da gerçekleşir. ROT’lar karbohidrat, nükleik asit, lipid ve proteinler gibi hücrenin temel makromolekülleri ile etkileşebilir. Proteinler canlı organizmalarda yapısal ve işlevsel olarak önemli rolleri üstlenmiş biyomoleküller olduğundan bu makalede protein ve serbest amino asitlerin ROT aracılığı ile oksidasyonu üzerinde durulmuştur. Proteinlerin oksidasyonu sonucu aromatik grupların ve alifatik amino asit yan zincirlerinin hidroksilasyonu, aromatik amino asit köklerinin ve sülfidril gruplarının nitrolanması, metiyoninin sülfoksitlenmesi, aromatik ve primer amin gruplarının klorlanması ve bazı amino asit köklerinin karbonil türevlerine dönüşümü gerçekleşir. Oksidasyon aynı zamanda çapraz bağlı proteinlerin oluşumu ve polipeptit zincirinin kırılmasına da neden olarak sonuçta bazı radikallerin en önemlisi alkoksil radikallerinin oluşumunu sağlar. Ayrıca proteinlerin fonksiyonel grupları 2-alkenal, 4-hidroksi-2-alkenal, and ketoaldehid gibi çoklu doymamış yağ asitlerinin oksidasyon ürünleri ve bazı karbohidrat türevleri (karbohidrat eklenmesi veya karbohidratların oksidasyon ürünleri) ile reaksiyona girerek inaktif türev bileşikleri oluştururlar. Diğer taraftan yaşlanma ve oksidatif hasara uğramış protein lipid ve nükleik asitlerin birikmesi arasında bir ilişki bulunmaktadır. Oksidatif olarak modifiye olmuş proteinlerin miktarında yaşın ilerlemesi ile birlikte artış olduğu ve protein oksidasyonunu azaltan faktörlerin aynı zamanda canlıların yaşam süresini uzattığı bilinmektedir. Ayrıca omurgalılarda diyabet, aterosklerosis, nörodejeneratif hastalıklar, kalp ve damar sistemi rahatsızlıkları gibi yaşlanmaya ve diğer çok sayıda hastalıklara bağlı protein oksidasyonu ürünlerinin fazla oluşumu sonucu hücre ve dokularda aşırı birikimi ile ilişkili olduğu gösterilmiştir. Protein oksidasyonu seviyesi çeşitli oksidatif stres faktörlerinden kaynaklanan bazı hastalıklar ve önemlisi yaşlanma sırasında miktarı yükselen protein oksidasyonun en önemli belirteci olan protein karbonil bileşiklerinin ve diğer son ürünlerin miktarının ölçülmesi ile belirlenebilmektedir.
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