Ahern's BB 350 at OSU - 6. Structure and Function of Hemoglobin
1. Contact - [email protected] 2. Kevin's lectures with The Great Courses - https://www.thegreatcoursesplus.com/b... 3. Kevin's Lecturio videos for medical students - https://www.lecturio.com/medical-cour... 4. Course materials at https://kevingahern.com/biochemistry-... 5. Course video channel at • Ahern's BB 350 at OSU - 1. Introduction 6. Metabolic Melodies at https://teeheetime.com/category/lyric... 7. Kevin's Free Biochemistry books - https://kevingahern.com/biochemistry-... 8. Kevin's Pre-med Audio course on Listenable - https://listenable.io/web/courses/143... Highlights Protein Structure II Highlights 1. Disruption of forces that stabilize protein structure cause folded proteins to unfold. Unfolded proteins are not functional. We describe them as denatured. Denaturing agents include heat, detergent, acid or base. 2. Fibrous proteins are proteins that have primary and secondary structure, but virtually no other structures. They are essentially long fibers or shees of secondary structure. Examples include collagen, keratin (hair), or silk. 3. Myoglobin is a protein that acts like a 'battery', storing oxygen in muscles until it is needed. It is related to the oxygen transport protein called hemoglobin, but does not have a signicant function in transporting oxygen - only storing it. 4. Myoglobin contains a functional group called 'heme'. Heme is composed of a ring called Protoporphyrin IX plus an iron atom. Heme is closely related to chlorophyll. Carbon monoxide can bind to the iron of the heme group. 5. Hemoglobin differs from myoglobin in containing four polypeptide subunits instead of one. Interactions between multiple polypeptide subunits of a protein are called quaternary structure. 6. Hemoglobin contains two alpha and two beta subunits, each carrying one heme molecule. Binding of an oxygen molecule by one subunit causes a slight conformational change in the subunit that causes a slight quaternary change that causes an adjacent subunit to bind oxygen with greater affinity. This is referred to as cooperativity. When hemoglobin is in the state of high affinity for oxygen (wants to bind oyxgen), we say it is in the R state. When it is in the low affinity state for oxygen (wants to release oxygen), we say it is in the T state. 7. Cooperativity requires multiple subunits. 8. In the lungs, the oxygen concentration is high, so hemoglobin easily gets loaded up with oxygen. In tissues, where oxygen concentration is low, one of the oxygens comes off of hemoglobin and the reversal of what happened above occurs. Loss of one oxygen by hemoglobin favors loss of the others and oxygen is dumped where it is needed. 9. Adult hemoglobin contains a pocket in the middle of it that can bind a molecule called BPG . BPG is produced by actively respiring tissues. When it is bound, hemoglobin loses some affinity for its oxygen (changes to T state) and lets it go. Hemoglobin drops BPG before it gets to the lungs and it is broken down readily, if you're not a smoker. In smokers, BPG is in greater abundance in the blood, so hemoglobin has reduced oxygen carrying capacity, due to more of it coming to the lungs bound to BPG and is thus locked in the T state. 10. The Bohr effect relates to the fact that hemoglobin loses affinity for oxygen in the more acidic the environment in which the hemoglobin is found. Any tissue, such as muscles, when actively using energy, produces acid. Thus active tissues get more oxygen dumped on them by hemoglobin, due to the Bohr effect. 11. When hemoglobin picks up protons near active tissues, it dumps the oxygen and picks up CO2, which it transports it back to the lungs. In the lungs, the protons and CO2 come off. They are actually forced off due to the high oxygen concentration. When CO2 comes off, it is exhaled. 12. Fetal hemoglobin differs from adult hemoglobin in that the two beta subunits are replaced by two gamma subunits. This changes hemoglobin's structure very slightly so that 2,3BPG can't bind. Consequently, fetal hemoglobin spends more time in the R state and can take oxygen away from adult hemoglobin. 13. Sickle cell anemia arises from a mutation in one of the hemoglobin subunits. This mutation causes hemoglobin to polymerize under low oxygen conditions and converts the blood cells into a sickle shape. They get stuck in capillaries when this happens.
