Chapter 7b The Bohr Effect CO2 Influences The Bohr Effect states that as pH goes down O2 affinity also goes down Therefore the Tense T State of hemoglobin is stabilized at lower pH A low pH also leads to a high p50 CO2 is transported by hemoglobin to the lungs as an amino terminal amide When CO2 is produced in the muscles it binds with water to form bicarbonate lowering the pH The Bohr Effect comes in to play and O2 affinity drops causing oxygen unloading in the cells This stabilizes the T state Bisphosphoglycerate BPG is an allosteric regulator it only binds to the T state stabilizing it Only with BPG bound does the p50 26 BPG dissociates in tissues Fetal Hemoglobin Fetal Hb has gamma globins rather than beta globins The gamma globins cause a higher O2 affinity needed in the fetus in order to cross the placental barrier Cooperativity Models The sequential model shows that the binding of the first O2 to Hb changes the shape of the molecule increasing the O2 affinity on the now exposed binding sites The symmetry model shows that O2 binding favors the conversion of all subunits to the high affinity state Both models explain the transition from the T to R states Sickle Cell Anemia Sickle cell anemia is caused by a mutation of a single site The glutamic acid in position 6 is mutated to a Valine This is a switch from a hydrophilic to a hydrophobic group The valine allows the molecule to fit into a pocket on another molecule causing long chains to form The shape is due to hydrophobic interactions between deoxy HbS tetramers This is in the deoxy state The polymerization is dependent on deoxyHbS 10 and reducing this percentage could eliminate sickle cell Only the homozygote shows symptoms the heterozygote is malaria resistant Muscle Fascicle Bundle Muscle Fiber cells Myofibril The sarcomere is the smallest unit of contraction in a myofibril It consists of thick myosin and thin actin chains Myosin is composed of 2 heavy chains and 4 light chains The light chains are Essential Light Chains as well as Regulatory Light Chains The myosin head is composed of 2 of these light chains as well as the N terminus of the heavy chain Actin polymerizes to form filaments which use ATP to slide across myosin during contraction When ATP binds to the myosin head the actin binding site is revealed allowing the chains to slide past each other When ATP is used a phosphate group splits off and the muscle relaxes Each time the myosin head moves along the actin filament in a ratcheting motion 1 ATP is used Antibodies Antibodies are synthesized in beta lymphocytes and protect us from foreign antigens There are as many as 1018 different antibodies The antibody antigen complex as a whole is destroyed when antigens are removed Antigens are composed of 2 heavy chains and 2 light chains Each chain has a variable as well as a constant domain The heavy chains are located on the outside and the light chains are in the middle of the Y shaped cleft The arms of the Y are called Fab Fragments Each antibody has a constant domain as well as a variable domain The variable domains are expressed as Vl light and Vh heavy The variable domains have hypervariable regions which come from multiple gene fragments combined to form a protein The Antibody Antigen complex is bound by VDW forces H bonding electrostatic interaction and hydrophobic interaction These forces form dissociation constants of about Kd 1010 very strong Antibodies collect at foreign material which in turn stimulates the production of more antibodies Antibodies are specific to their antigens Chapter 8 Carbohydrates Carbohydrates CH2O n have four different uses 1 Energy Glucose glycogen starch 2 Structure Cellulose majority cell walls chitin 3 Recognition Antigens 4 Regulation through glycosylation Become active inactive Monosaccharides Aldoses C1 is an aldehyde CHO In aldoses 3 carbons is a triose followed by tetrose pentose hexose etc Ketoses Again triose tetrose etc C2 is a ketone Monosaccharides Continued Isomers Identical formula but ordered differently Stereoisomers differ in 3D space Enantiomers Mirror images carbonyl Diastereomers Not mirror images Epimers Differ at single site D L sugars designation based on chiral center furthest from Anomers Differ at the anomeric carbon After cyclization Alpha Beta designation Pyranose 6 membered ring Furanose 5 membered ring When reacting with alcohols the aldehyde ketone will form a hemiacetal ketal Monosaccharides can undergo several modifications For example glucose can be oxidized to form gluconic acid They can also be reduced acetylated sulfonated etc Disaccharides Monosaccharides bond at the anomeric carbons to form a disaccharide such as sucrose or lactose The bond between is called the glycosidic bond When the bond is between 2 anomeric carbons the sugar is non reducing When naming these structures we use the suffix syl for the first sugar and side for the second For Sucrose Note that the 2nd ring has been flipped Sucrose is a combination of glucose and fructose In naming we will call it D glucopyranosyl 1 2 D fructofuranoside galactopyranosyl 1 4 D glucopyranoside For Lactose D The anomeric end of the compound is known as the reducing end The sugar is a reducing sugar if it is exposed such as in lactose and is a non reducing sugar when unexposed such as in sucrose Polysaccharides Starches The purpose of starch is energy storage Amylose is several thousand unbranched alpha 1 4 inked glucoses that form a large coil in a left handed helix Glycogen has alpha 1 6 branches every 10 residues and alpha 1 4 glucose links The branching is important for access to non reducing sites Cellulose is again 1 4 linked glucose but in beta form The beta links allow the cell to have extensive hydrogen bonding for stabilization in large sheets Heparin is a highly sulfonated anticoagulant Hyaluronate is a natural shock absorber found in the vitreous humors of the eyes and in synovial fluid It uses an oxidated and amidated residue linked beta 1 3 Proteoglycans have a huge molecular weight structures and are highly hydrated They are an important part of cartilage for shock absorption Proteoglycans Bacterial Cell Wall The bacterial cell wall is a combination of saccharides and peptides including D amino acids The framework is known as a peptidoglycan and is very rigid Glycoproteins of Eukaryotes Many proteins secreted and within the eukaryote membrane are glycosylated outside of the cell The oligosaccharides are bound to the proteins with