BIOCHEMISTRY PDF

17 Noor Aldeen Alfaouri & Hala Abu-Dyouk Lujain Al-awamleh Dr.Nafez Abutarboush 1  Proteins General speak… o Proteins differ from all other macromolecules, because they change their shape by binding to other macromolecules, small mol...

17 Noor Aldeen Alfaouri & Hala Abu-Dyouk Lujain Al-awamleh Dr.Nafez Abutarboush 1  Proteins General speak… o Proteins differ from all other macromolecules, because they change their shape by binding to other macromolecules, small molecules, or atoms, or by altering their environment. o Each protein has an enormous number of conformations, because even a small change —whether in binding, the environment, or any other factor can lead to changes in its shape. o Changes in conformation lead to changes in function, either totally or partially, so the activation or inhibition of the protein depends on these changes. o Among these confirmations, there should be at least one fully active confirmation (which may be more than one), named native confirmation, (100% active). o As we mentioned before, change in structure cause changes in function (even if the change is small). o Levels of protein structure (primary, secondary, tertiary and quaternary) depend on the development of the structure, meaning how these proteins are being built up. o The Primary structure (the base) of protein determines how the final shape of protein will be. o Stages for building a protein: a) To make the base: which is controlled by number of amino acids that we have, types of these amino acids, and their sequence, which form a linear shape (primary structure). b) Close areas start wrapping around each other through the protein backbone, each structure should be described by its bonds. 2 So, let’s start describing these different levels: Primary structure by covalent bonds only (Peptide bonds). Secondary structure close areas start rotating around themselves in a specific way through their backbones which are already bounded through peptide bonds. And it has nitrogen and oxygen atoms, which can participate in hydrogen bonds, giving special arrangement of amino acids. ( the localized organization of parts of a polypeptide chain) (Only hydrogen bonds can be formed) Tertiary structure connecting far areas by disulfide bonds (the only covalent bond that might be interact in this structure), hydrogen bonds, hydrophobic interactions, ionic interactions or van der Waals interactions to give the final shape. (the three-dimensional structure and/or arrangement of all the amino acids residues of a polypeptide chain) It may include metal ions and may be connected to other structures. (Any bond can be formed) Note: the previous 3 protein structures are How do we know if a protein formed only when the protein has only 1 contains one or more polypeptide chain. polypeptide chains? Answer: If there is more than one (N- ‫بحالة إذا كان البروتين بتكون‬final shape ‫بعتبره هون ال‬ terminal and C- terminal), so it has ‫ فقط‬one polypeptide chain ‫من‬ more than one polypeptide chains. Note :One subunit, one monomer, and one polypeptide chain are all the same terms. The quaternary structure :consists of more than one polypeptide chain, bound by any types of bonds. These are known as multimeric proteins. In hemoglobin, when more than one subunit is connected together (four subunits), their function is maximized, because each subunit has a specific function. When these subunits are connected, the bonds between them influence their function, increasing the number of conformational changes (Many Quaternary structural proteins CANNOT form covalent 3  bonds because they are strong and rigid preventing this molecule to do its function as well). Note: other quaternary structures may have covalent bonds depending on what their function requires. )covalent bonds( ‫) وكان عدد الروابط التساهمية‬quaternary structure( ‫إذا كان في بروتين يحتوي على هيكل رباعي‬.‫استقرارا ولن يتعرض للكثير من التغيرات‬ ً ‫ فإن هذا البروتين سيكون أكثر‬،‫كبيرا‬ ً The primary structure: The primary structure refers to the sequence in which amino acids are covalently linked together, forming a linear chain. The primary structure of a protein determines its higher levels of structure (secondary, tertiary, and quaternary). There is a degree of similarity between the primary structures of proteins that perform similar functions (e.g., the subunits of hemoglobin and myoglobin). Because of the similarities between the primary structures of the proteins, we can predict the final structure of this protein (It is not necessarily that we always predict it correctly) Both proteins serve similar functions, with slight differences: Myoglobin: Supplies oxygen to muscle cells. Hemoglobin: Delivers oxygen to body tissues. 4 Q: How does the primary structure affect the final shape of the protein? Let’s take hemoglobin as an example. Hemoglobin has 4 subunits (2 Alpha and 2 Beta), and each of these subunits has its own primary structure. A single amino acid substitution in the primary structure of the Beta subunit can lead to a malfunctioning protein, as seen in the case of sickle- cell anemia. Sickle-cell anemia is caused by a change in the 6th amino acid position of the Beta globin chain (glutamic acid to valine). Why does this happen? Glutamic acid is negatively charged and is located on the outer surface of hemoglobin. When two hemoglobin molecules come close to each other, they repel each other, and each molecule moves freely without interacting. However, when valine replaces glutamic acid, the two hemoglobin molecules are now attracted to each other through hydrophobic interactions. As a result: 1. Hemoglobin molecules aggregate. 2. Red blood cells deform into a sickle shape. 3. Clotting can occur in blood vessels and tissues. ‫ في حالة فقر الدم‬.‫ا لتغيير في ترتيب األحماض األمينية في الهيكل األولي للبروتين يمكن أن يؤدي إلى تغيير في شكله ووظائفه‬ ‫ مما يؤدي إلى تشوه خاليا الدم‬،‫ استبدال حمض الجلوتاميك بالفالين في الهيموغلوبين يجعل الجزيئات تتجمع بدالً من التنافر‬،‫المنجلي‬.‫ هذا التغيير يسبب تجلطات في األوعية الدموية ويؤثر على نقل األوكسجين‬.‫الحمراء وتكوين شكل منجلي‬ 5 ‫تمت كتابة هذا الشيت عن روح والدة زميلنا عمرو رائد من دفعة تيجان‬ ‫دعواتكم لها بالرحمة والمغفرة‬ ‫‪Thank you‬‬ ‫‪6‬‬