Essential Elements of Biochemistry BCHM 3050 Dr Srikripa Chandrasekaran Dr Sri Lecture Notes 1 28 15 Proteins con t Mad Cow Prions Proteinaceous Infectious Particles Consuming the pre prions or the prions could be very dangerous Pre prions are dormant prions that can become actual prions Prions have a lot of beta sheets more than a typical protein has Fibrous proteins Typically contain high proportions of helices and pleated sheets Often have structural rather than dynamic roles and are water insoluble o Keratin helices and silk fibroin sheets Generally insoluble in water Function structure support not necessarily any specific job Fibrous proteins do not engage in enzymatic jobs globular proteins typically carry out the jobs in which enzymes are needed Fibrous proteins do not usually go through a rigorous folding process like globular proteins do They are very simple and typically just stay at the secondary structure form Collagen part of the connective tissues matrix Left handed helices twisted to form a right handed triple helix o Impart special properties to structures e g bone and skin o Glycine and proline and hydroxyproline are common amino acids Helices come together to form collagen Glycine and proline are common amino acids in alpha helices you typically do not find glycine and proline because they are helix breakers This is different than normal helices Collagen and aging Loss of crosslinks e g lysinorleucine with age Lysine and leucine come and cross each other in order to create lysinorleucine When these crosslinks are lost the skin becomes softer and wrinkles form Lysine is a basic amino acid Leucine is a non polar amino acid A lot of skin product companies work on ways to prevent the loss of these crosslinks Globular proteins structure and function of myoglobin vs hemoglobin Same heme prosthetic group to bind oxygen Very similar polypeptide tertiary structures Very similar functions oxygen transport Myoglobin is a monomer hemoglobin is a tetramer 1 Different physiological locations affinities from oxygen kinetics of binding and dissociation of oxygen Although Mb Hba Hbb are very similar only 22 AA s are identical in all three so AA compositions are actually quite different but it s the 3D shape that s conserved including the hydrophobic pockets Mb 153 Alpha Hb 141 AA s Beta Hb 146 AA s Note that there are approx 83 AA differences between HbA HbB subunits Myoglobin and hemoglobin are responsible for getting oxygen to different places throughout the body Functional relations between myoglobin and hemoglobin The lungs are the site of oxygen exchange Red blood is oxygenated Blue blood is deoxygenated Hemophilia Hemoglobin is not able to maintain oxygen the hemoglobin is saturated with carbon dioxide blue blood the Royal British family used to suffer from this because they would intermarry within the family ex cousins would marry cousins incest Hemoglobin is more active in the lungs myoglobin is more active in the muscle tissues cells Myoglobin is found in cardiac muscles hemoglobin is found in red blood Hemoglobin has lower affinity for oxygen than myoglobin Blue blood just refers to a lot of veins because blood in veins is deoxygenated and contains a lot of CO2 Dangerous for people with hemophilia to have cuts and lots of bleeding Myoglobin 8 helices Found in skeletal and cardiac muscles Stores oxygen has higher affinity for oxygen compared to hemoglobin Fewer binding sites more affinity for oxygen myoglobin Hemoglobin helices and 2 helices 2 Found in red blood cells Transports oxygen from lungs to tissues More binding sites lower affinity for oxygen hemoglobin Hemoglobin s lower affinity for oxygen allows it to dump oxygen to Cooperative oxygen binding myoglobin Heme consists of a porphyrin ring composed of four pyrroles with Fe2 in the center Factors affecting the amount of O2 bound by hemoglobin 1 Availability of oxygen i e concentration or partial pressure of O2 2 Binding of first O2 molecule i e cooperativity 3 pH 4 Presence of CO 2 Hemoglobin depends on how tightly the first oxygen can bind to the site Oxygen binding equilibrium curves for myoglobin vs hemoglobin Refer to the graph displayed in the PowerPoint Myoglobin has a hyperbolic curve signifies higher affinity for oxygen In hemoglobin it needs larger concentrations of oxygen in order to reach saturation A working muscle needs oxygen so myoglobin takes oxygen from hemoglobin We do not have myoglobin in the lungs Under arterial pressures when blood has just received O2 from lungs hemoglobin is fully saturated with O2 As blood pressure decreases further from heart closer to veins tissues where O2 is needed low Hb has less affinity for O2 and is releasing it Note Binding release of O2 by Mb occurs at even lower PP s of O2 Essentially this means that Mb has a much higher affinity for O2 than Hb Mb will take its O2 from Hb and only give it up in the tissues that are even more depleted of O2 Partial pressure of O2 in air 160 mm Hg Effects of pH on O2 binding H ions decrease hemoglobin s affinity for O2 Sources of H ions include bicarbonate buffering system and lactic acid production Both CO2 and lactic acid accumulate in tissues that are in need of O2 Glucose Pyruvate Lactic Acid CH3CHOHCOOH Low pH promotes release of O2 high pH stabilizes HbO2 CO2 H2O HCO3 H CH3CHOHCOO H Anaerobic respiration lowers the pH and causes the accumulation of lactic acid lowering of pH dissociates hemoglobin from oxygen The process of fermentation creates lactic acid At low pH hemoglobin does not bind to oxygen very tightly Lactic acid accumulates in muscles that are over worked oxygen does not have a chance to reach the muscles anaerobic respiration creates lactic acid Effects of pH on O2 binding The Bohr Effect Low pH high CO2 high lactic acid decreases Hb affinity for O2 H ions displace O2 bound to Hb HbO2 H HbH O2 The Bohr Effect is named after Christian Bohr who first described phenomenon in 1904 Christian Bohr was the father of Niels Bohr famous physicist known for theory of atomic structure quantum mechanics and Harold Bohr famous mathematician Haldane Effect the binding of O2 to hemoglobin promotes the dissociation of CO2 from hemoglobin 3 Refer to graph in PowerPoint The orange line represents the hemoglobin the more the curve shifts to the right the lesser the affinity for oxygen becomes less hyperbolic as it shifts to the right lower the pH the lower the affinity for oxygen Effects of carbon monoxide on O2 binding CO
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