BIOCHEMISTRY Sheet 21 PDF 2024

21 Sara Maher Besan Alameir Dr Nafez Abutarboush 1  Structure-function relationship Globular proteins (Myoglobin and hemoglobin) Unlike fibrous proteins (which are repeated identical secondary structure), Globular proteins shouldn’t be packed...

21 Sara Maher Besan Alameir Dr Nafez Abutarboush 1  Structure-function relationship Globular proteins (Myoglobin and hemoglobin) Unlike fibrous proteins (which are repeated identical secondary structure), Globular proteins shouldn’t be packed well; How? by containing different structure inside. -Myoglobin and Hemoglobin are the exception that include only one type of secondary structure which is alpha helix (they are exception, but the final shape is globular) -The driving force of their formation (globular proteins) is the hydrophobic interactions (non-polar inside and polar outside) The function of Myoglobin and Hemoglobin Myoglobin is storage of O2 in muscles and other tissues (During periods of oxygen deprivation, oxymyoglobin releases its bound oxygen) Hemoglobulin is transport of O2 and CO2 and blood buffering AFFINTY TO BIND TO O2 ‫الفرق الفعلي بيناتهم بتعلق بال‬ Myoglobin has higher affinity CUZ OF the storge function of it ‫يعني هو بخزن االوكسجين فبحاجة يضل عنده فترة أطول من الهيموغلوبين الي هو فقط وسيلة نقل لالوكسجين (وأصال إذا‬ Myoglobin ‫كانوا نفس االفينيتي ما رح يصير انتقال لالوكسجين) وكل ما النسيج يكون بحاجة اوكسجين اكثر بكون عنده‬.‫اكثر‬ O2 ‫ وهذا هو السبب انه احنا بنتنفس‬electron transport chain ‫نحتاج األوكسجين عشان‬ Myoglobulin Myoglobin was first protein that could be characterized structurally. -It’s a monomeric protein that mainly found in in muscle tissue. -It includes a prosthetic group, the heme group -Myoglobulin tertiary structure consists of 8 α-helices (sequenced from A to H) that connected by short non- helical regions. 2 -like other globular protein, the R groups in Amino acids exposed on the surface of the molecule are generally hydrophilic while those in the interior are predominantly hydrophobic, except for two Histidine residues in helices E & F (known as E7 & F8) F8 His is proximal His and E7 His is Distal one. It can be present in two forms: -Oxymyoglobin (oxygen-bound) -Deoxymyoglobin (oxygen-free) Myoglobin shared with Hemoglobin the structure which called Heme Heme group -Large macrocyclic ring that includes iron in the middle -large macrocyclic ring consist of 4 pyrrole rings and each pyrrole ring has Nitrogen which gets attached to the iron. -it is a prosthetic group (highly attached) (a non protein group covalently attached to a protein) -Heme is a flat molecule that has 4 cyclic groups known as pyrrole rings. -Upon absorption of light heme gives a deep red color ‫( أو لون بني وإذا بدلنا الحديد بالمغنيسيوم رح يعطينا‬urine color( ‫ رح يعطينا لون اصفر‬heme‫اذا تكسر ال‬.‫الكلوروفيل‬ -Both myoglobin and hemoglobin are hemoproteins (a group of specialized proteins containing heme as a tightly bound non-protein group known as a prosthetic group) The protein environment dictates the function of the heme. more clarification: proteins that have heme group called hemoproteins, and they have classification according to function of the proteins (ex: binding proteins; the function of their heme is binding to things like myoglobin and hemoglobin proteins that bind to O2; enzymes as catalytic hemoprotein) 3  cytochrome ‫ وظيفته فقط نقل اإللكترونات بنسميه‬heme ‫يسمى البروتين الذي يحتوى على‬ Iron -Fe is in the ferrous state (Fe+2) can form 6 bonds (max number but it's not necessary to bind to all the 6) Iron in heme forms 4 bonds with the nitrogen of the center of rings and one (known as 5th coordinate) with the nitrogen of Histidine imidazole by ligation bond (known as proximal His or F8 as mentioned before), and one with O2 (6th coordinate) Oxidation of iron to the Fe3+, ferric, state makes the molecule incapable of normal O2 binding. Note: We have a classification of the heme according to the number the bonds that iron bind to (4th, 5th, 6th coordinate heme) -if we have the heme by itself (preheme) outside the protein then it's 4th coordinate (ligated) heme.‫ روابط‬4 ‫الحديد بالهيم نفسه بدون ما يكون جوا البروتين بكون‬ -if the heme inside the protein, then it's 5th coordinate heme like Myoglobin & Hemoglobin cuz they are binding proteins and 6th position is always available for binding O2..‫وركزا تفهموا الفكرة تبعت التصنيف ممكن ييجي عليها سؤال‬ Structure-function relationship The planar heme group fits into a hydrophobic pocket of the protein and the myoglobin-heme interaction is stabilized by hydrophobic attractions. Note: the heme is not amino acid, so the folding of protein occurs and then the heme being synthesized and inserted inside this pocket. This hydrophobic pocket stabilizes the heme in its place. 4 ‫‪The heme group stabilizes the tertiary structure of myoglobin.‬‬ ‫‪-The proximal His (F8) binds to the iron in the heme.‬‬ ‫‪The distal histidine (E7) acts as a gate that opens and closes as O2 enters the‬‬ ‫‪hydrophobic pocket to bind to the heme.‬‬ ‫‪The hydrophobic interior of myoglobin (or hemoglobin) prevents the oxidation of iron, and‬‬ ‫‪so when O2 is released, the iron remains in the Fe (II) state and can bind another O2‬‬ ‫اشرحلكم الفكرة عنا حديد جوا الهيم عنده اإلمكانية يكون ‪ 6‬روابط كحد أقصى ; ‪ 4‬روابط بتكونوا مع النيتروجين الموجود‬ ‫ضمن ال ‪ 1 + pyrrol rings‬بتتكون مع الهستيدين الموجودة في ‪ alpha helix number 8‬والي سميناها ‪ F‬حسب‬ ‫ترتيبها طيب ليه برتبط معها؟ ألنها أقرب‪ +‬السادسة بتتكون مع االكسجين‪.‬‬ ‫طيب شو فائدة الهستيدين الموجود على ‪ Alpha helix number 7‬والي سميناها ‪ E‬والي اعتبرناها االبعد عن الهيم‬ ‫بداية الوضع األكثر استقرارا الرتباط االكسجين مع الرابط السادسة في الحديد هي وضعية قائمة ‪ 90‬درجة‬ ‫(‪)the highest affinity for O2‬‬ ‫بس انا ما بدي ياها مستقرة لدرجة ما تفك بعدين بس نحتاجها ألنه هاد ما بتناسب مع وظيفته المتمثل بالربط والفك وهون‬ ‫بيجي دور ‪ the distal His‬والي بتكون بعيدة مسافة انها تأثر على الهيم بس ما ترتبط مع الحديد فبصير ارتباطهم فيه‬ ‫ميالن مش عامودي ومش مستقر أكبر استقرار )‪)less affinity‬فبصير عنا ‪releasing for O2 when we need‬‬ ‫‪ ، that‬تطلعوا على الصورة لتساعدكم تفهموا‪.‬‬ ‫مالحظة‪ :‬مهم تعرفوا انه لما يصير تبادل بين الغازات ال ‪ CO2‬ما برتبط مكان ال‪ O2‬بالهيم هو برتبط ‪in N terminals‬‬ ‫على البروتين نفسه يعني فعليا مالهم عالقة ببعض ‪ ,‬لكن اللي إله عالقة هو ال‪ CO‬والي ممكن يرتبط مكانه ألنه ‪much‬‬ ‫‪ higher affinity than O2‬ويقلل مستوى االكسجين في الجسم زي ما بصير في حاالت االختناق‬ ‫‪5‬‬ Oxygen binding to myoglobin -Myoglobin binds O2 with high affinity. -The P50 (oxygen partial pressure required for 50% of all myoglobin molecules to be saturated) for myoglobin ~2.8 torrs or mm Hg. -Given that O2 pressure in tissues is normally 20 mm Hg, it is almost fully The binding of O2 to myoglobin follows saturated with oxygen at normal hyperbolic saturation curve conditions. We notice that in a very small change in X axis I achieve very high change in Y axis which means I get very high level of saturation by little amount of O2 what tells me that Myoglobin have very high affinity for O2. ‫تمت كتابة هذا الشيت عن روح والدة زميلنا عمرو رائد من دفعة تيجان‬ ‫دعواتكم لها بالرحمة والمغفرة‬ Thank you 6