Concepts for Exam 1 PDF

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Instructor: Dr. Potenza...

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Ionization of water and weak interactions -Carbon can form up to 4 covalent bonds -Hydrogen can form up to 1 covalent bond -Oxygen can form up to 2 covalent bonds -Nitrogen can form up to 4 covalent bonds -Polar molecules dissolve easily in water because the atoms in a polar molecule replace water – water interactions with more favorable interactions -hydrogen bonds are 10% covalent + 90% electrostatic -vaan der wals, hydrophobic + H bonds are weak non-covalent interactions -A hydronium ion is a hydrated hydrogen ion, the usual form for one of the dissociation products of water in solution and is a hydrated proton. -According to Segel, in every ionization of an acid or base a conjugate acid or conjugate base pairs are involved -the equilibrium constant, Keq, is defined as the concentration of the products dived by the concentration of the reactants at the position of equilibrium for a chem rxn -water derives all its special properties from its polarity + H bonding capacity -Hydrophobic interactions make important energetic contributions to binding of a hormone to its receptor protein, enzyme substrate interactions, 3D folding of a polypeptide chain and membrane structure -osmosis is movement of a water molecule across a membrane Physiological pH range and biological buffers -associating with –log[H+], its scale designates the [H+] and [OH-] and each increase or decrease in pH by 1 represents a 10-fold change in [H+] -titration curves allow the determination of weak acids pka’s -when pH = pKa, the weak acid and salt concentrations in a buffer are equal -the henderson-hasselbach equation relates the pH of a solution to the pKa and the concentrations of acid + conj base -the amino acid Histidine has 3 pKas -The [H+] in a urine sample that has a pH of 6 is 10-6M -phosphoric acid is tribasic, w/pKa’s of 2.14, 6.86 and 12.4. The ionic form that predominates at pH 3.2 is H 2PO4Approximately, 300 additional amino acids have been found in cells -because amino acids can act as acids and bases, they can act as biological buffers both as part of a protein and as an individual residue -the predominant form of glycine at its pI is zwitterionic -information provided by titration curves include how many ionizable groups each amino acid contains, the best buffering zones foreach amino acid are w/in 1 pH unit on either side of the pKa’s, and show all amino acids are positively charged at very low pH -titration of valine by a strong base (NaOH) reveals 2 pK’s: the titration occurring at pK2 = 9.62 is NH3 + + OH --> NH2 + H2O -All individual amino acid are soluble in water but not all peptides are soluble because individuals amino acids are zwitterions at physiological pHs -The chirality of an amino acid results from the fact that its alpha carbon is bonded to 4 different chemical groups -methionine and cysteine contain sulfur atoms -on a molar basis, tryptophan absorbs more UV light than tyrosine -cysteine forms when the CH2-SHR group is oxidized to form a CH2-S-S-CH2 disulfide bridge b/w 2 cysteines Peptides and Proteins -At the isoelectric pH of a tetrapeptide the total net charge is O -The formation of a peptide bond between 2 amino acids is an example of a condensation reaction -when you study the spatial arrangement of proteins the functional, folded structures are called native proteins -A protein’s native structure has hydrophobic interactions that predominate, increase the order of water in the solvation layer that results in a decrease in the entropy of the water, and has interaction of charged R groups in residues that can have a stabilizing or destabilizing effect on protein structure -The Ramachandran plot takes into account double bond characteristic of the peptide bond -the backbone arrangement of 2 peptide bonds is usually C-α-C-N-C-α-C-N

-there are S proteins in table 3-2 in lehinger text that exhibit 4° structure -with respect to the amino acid composition of proteins, proteins, w/different functions usually differ significantly in their amino acid composition -prosthetic groups in the class of proteins are known as glycoproteins that are composed of carbohydrates Protein secondary structure --protein structure (2°) refers to any chosen segment of a polypeptide chain and the local spatial arrangement of its main chain w/out regard to the positioning of its side chains or its relationship to other segments. -although non-regular secondary structure is sometimes referred to as undefined or random coil, this is a misnomer because, the path of most pp backbones is not random but, unchanging and highly specific to the structure and function of that particular protein -the α-helix forms more readily than many other possible conformations in part because of the optimal use of internal hydrogen bonds. -Not all pp’s can form from a stable α-helix. Positively charged residues found in 3 residues away from negatively charged residues might be found in α-helices -antiparrallel beta sheets might be more stable than parallel beta sheets based on figure 4-6, the H-bonds are better aligned in antiparrallel β-sheets -Domains are protein regions that can fold and function as an independent entity from the whole protein -The structural classification of proteins (based on motifs) is based primarily on their 2° structure content and function -H-bonds b/w spring residues and the aqueous surroundings are possible contributors to the stability of the 3° structure of a globular protein -the average molecular weight of the 20 standard amino acids is 138, but biochemists use 110 when estimating the # of amino acids in a protein of known molecular weight because 110 reflects a higher proportion of small amino acids in proteins as well as the loss of water when the peptide bond forms -one method used to prevent disulfide bonds interference w/protein sequencing procedures is reducing disulfide bridges and preventing their reformation by further modifying the SH groups Protein Motifs, structure and folding -A super secondary structure, a fold or a motif is a recognizable folding pattern involving two or more elements of 2° and the connection b/w them -hydrophobic interactions make a large contribution to the stability of protein structures, therefor, burial of hydrophobic amino acid residues needs at least 2 layers of 2° structure -according to SCOP2: protein tertiary structure is more reliably conserved than amino acids sequence -amino acid sequences provide important BioChem information but exactly how the amino acid sequences determine 3D structures is poorly understood -About 20-30% of proteins in humans have polymorphic sequence variance that have little to no effect on function -domains may retain their correct shape when separated from the rest of the protein. -proteostasis is the cellular process by which protein levels are maintained -proteins are classified w/in families or super families based on similarities in structure and or function -disulfide interchange, chaperonins, heat shock proteins and peptide bonds isomerization is known to be involved in the process of assisted folding of proteins -Experiments of denaturation and renaturation after the reduction and reoxidation for the S-S bonds in the enzyme RNAse have shown that the primary sequence of RNAse is sufficient to determine its specific 2° and 3° structure. Ligand Binding and Myoglobin -The interactions of ligands w/proteins are usually transient -a molecule bound reversibly by a protein is called a ligand. A ligand could e, a steroid, drug or another protein -The binding site of a protein ‘breathes’ w/ligand biding -A prosthetic group of a protein is a non-protein structure that is permanently associated w/the protein -In the binding of oxygen to myoglobin, the relationship b/w the concentration of oxygen and the fraction of binding sites occupied can be best described as hyperbolic -The larger the Ka in protein-ligand binding, the smaller the Kd (dissociation constant)

-the graphical representation of ligand binding … proteins w/a single ligand binding site shows that the [L[ at which half of all available sites are occupied equals the ligands 1/Ka -protoporphyrin is the organic portion of the heme group in hemoglobin -myoglobin stores oxygen in muscle cells -The partial pressure of O2 (pO2) is a factor that influences the binding of Oxygen to myoglobin Ligan binding and Hemoglobin -Myoglobin and the subunits of hemoglobin have very similar 3° structures but different 1°structures -The R or ‘relaxed’ state is stabilized by the binding of O2 -the T or ‘tense’ state is stabilized by a greater # of weak non-covalent interactions that the R state -The ion pairs that stabilize the T state of hemoglobin occur b/w the α1 and α2 chains, the β2 and αβ1 chains and the α2 and intra-βchains -allosteric proteins can also bind modulators. Modulators are: inhibitors or activators -in addition to carrying nearly all the oxygen required by cells from the lungs to the tissues, hemoglobin carries 2 other end products of cellular resp. H+ and CO2. [H+] is high in peripheral tissues --> decreases pH and decreasing affinity of hemoglobin for oxygen -the stabilizing ion pair, protonated HC3-AspFG1, gives the HC3 an abnormally high pKa in the T state -the amino acid substitution of Val for Glu in Hemoglobin S results in aggregation of the protein because of hydrophobic interactions b/w molecules -BPG (2,3 biphosphoglycerate) binds at a distance from the heme groups of hemoglobin, binds w/lower affinity to fetal hemoglobin than to adult hemoglobin and is an allosteric modulator -hemoglobin exhibits cooperative binding of O2 while myoglobin does not -hemoglobin-binding of oxygen is best described as a combination of sequential and concerted models -The Bohr effect is the regulation of hemoglobin-binding by H+ ions and carbon-dioxide...