Analyse the role of NAD(P)H cofactors in fatty acid biosynthesis, specifically focusing on the enzymes involved in removing and adding functional groups. How do these enzymatic reactions contribute to the elongation of fatty acid chains? |
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Analyse the role of spectroscopies like absorbance spectrometry and NMR in assay design, highlighting their strengths and limitations. |
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Analyse the significance of genetic variations in drug efficacy, using metoprolol's activity changes based on beta-1-adrenergic receptor differences as an example. How can personalized medicine account for these variations in treatment? |
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Compare and contrast the Brønsted-Lowry theory and the Lewis theory of acids and bases, highlighting their key differences and applications in enzyme catalysis. |
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Compare and contrast the fatty acid synthetase types I and II in terms of their catalytic mechanisms and distribution in different organisms. How do these two types differ in their approach to fatty acid biosynthesis? |
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Compare and contrast the functions of different prokaryotic DNA polymerases, highlighting their specialized roles in DNA replication. |
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Compare and contrast the mechanisms of action between monoclonal antibodies and ligand mimics in drug design. How do these different approaches impact the treatment of various diseases? |
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Compare and contrast the mechanisms of action of triclosan and diazaborine inhibitors on ENR. How do these inhibitors differ in their approach to enzyme inhibition? |
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Compare and contrast the use of continuous flow and stopped flow methods in analysing enzyme-substrate reactions. Discuss the advantages and limitations of each approach. |
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Compare and contrast the use of different quenching agents in stopping reactions and quantifying compounds. |
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Compare and contrast Watson-Crick base pairing with Hoogsteen base pairing in the context of DNA polymerase accuracy. How does the active site of DNA polymerase favour Watson-Crick pairing over Hoogsteen pairing? |
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Define and explain the concept of half-life in biochemical kinetics. How is it calculated, and what does it signify about the reaction process? Provide a real-life example to illustrate the concept. |
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Describe the chemical modification studies conducted on RNase A, specifically focusing on the binding of iodoacetate to histidine residues and its implications on the enzyme's function. |
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Describe the concept of dead time in faster reactions and how it is determined. Provide examples of methods used to minimize dead time in reaction kinetics. |
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Describe the concept of sp3 and sp2 hybridization in carbon atoms. How does hybridization affect the geometry and bonding properties of carbon compounds? |
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Describe the mechanism by which DNA polymerase ensures fidelity during DNA replication. How does the steric gate, specifically the Phe residue, contribute to the accurate selection of nucleotides? |
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Describe the mechanism of action of peptide deformylase (PDF) in bacterial protein synthesis. How does the coordination of metal ions influence PDF's enzymatic activity? |
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Describe the process of enzyme activation by proteolysis and the role of inhibitor proteins in controlling protease activation. Use chymotrypsinogen as an example to illustrate the activation cascade. |
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Describe the process of lesion bypass using trans-lesion synthesis polymerases and its importance in DNA replication. |
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Describe the process of quenched flow and its application in studying reactions. Explain how temperature can be utilized as a quencher in this method. |
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Describe the process of RNA self-cleavage in alkaline conditions and why RNA is more susceptible to breakage in basic environments. Discuss the formation of pentaphosphate intermediates during this process. |
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Describe the process of structure-based drug design using HIV protease inhibitors as a case study. How can understanding the molecular structure of a target enzyme lead to the development of effective drugs? |
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Describe the role of antagonists and agonists in receptor signalling. How do these ligands interact with receptors at orthosteric and allosteric sites? Provide examples of how drugs can modulate receptor activity. |
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Describe the role of fluorine in modulating drug metabolism. How does fluorine substitution affect the bioavailability of a drug by decreasing its metabolism? |
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Describe the role of human serum albumin (HSA) in carrying hydrophobic molecules in the body. How does this process help in overcoming the issue of drug solubility in the blood? Provide a comprehensive explanation with relevant illustrations. |
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Describe the role of IC50 in enzyme inhibition. How does IC50 differ from EC50, and how is it used to determine the potency of an enzyme inhibitor? |
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Describe the stereospecific nature of hydride transfer in enzymatic reactions, focusing on the enzyme's ability to differentiate between hydrogen atoms. How does the distance and angle of transfer influence the efficiency of the reaction? |
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Describe the structural features of the 'hotdog' fold in FabA and FabZ reductases. How does this unique fold contribute to their catalytic activity? |
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Discuss the advantages and disadvantages of using direct assay methods versus quenching techniques in quantifying reactions. |
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Discuss the assumptions underlying the Michaelis-Menten model in enzyme kinetics. How does the assumption that k-1 is much greater than k+2 impact the interpretation of enzyme-substrate interactions? Provide examples to support your discussion. |
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Discuss the challenges associated with developing antibiotics targeting ENR due to the differences in structure between bacterial and human enzymes. How can these challenges be overcome in drug development? |
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Discuss the difference between the associative and dissociative mechanisms in nuclease enzymes, and explain how the nature of R groups influences their occurrence. Provide examples to support your explanation. |
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Discuss the discovery and significance of DNA polymerase I. How does the structure of DNA polymerase resemble a right hand, and what are the roles of the finger, thumb, and palm domains in DNA replication? |
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Discuss the impact of allosteric modulators on enzyme activity, considering both positive and negative effects. Provide examples of how these modulators can affect substrate binding and catalysis. |
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Discuss the impact of fluorination on a drug's lipophilicity and metabolic stability. How does fluorine substitution affect the bioavailability of a drug? |
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Discuss the importance of different drug structures, such as rings, charged groups, hydrophobic residues, and H-bond forming groups, in interacting with target proteins. How do these interactions contribute to drug binding? |
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Discuss the importance of Lipinski's 'rule of 5' in drug discovery and how it applies to small molecule drugs. Provide examples to support your explanation. |
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Discuss the importance of resonance structures in molecules like benzene and amino acids. How do resonance structures contribute to the stability and properties of these compounds? |
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Discuss the naming conventions for enzymes and the significance of naming enzymes based on their catalytic reactions. How has the transition to EC numbers impacted enzyme classification? |
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Discuss the principle behind flash photolysis and its application in triggering reactions. Provide examples of reactions that can be studied using this method. |
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Discuss the relationship between substrate concentration, enzyme affinity, and IC50 values. How does substrate concentration impact the observed IC50 value in enzyme inhibition studies? |
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Discuss the role of allosteric modulators in enzyme activity regulation. How do allosteric modulators differ from competitive inhibitors in terms of binding sites and effects on enzyme function? |
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Discuss the role of exonuclease activity in DNA Polymerase III and how it contributes to error detection and correction. |
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Discuss the role of hydride ions in oxidoreductases of fatty acid biosynthesis, comparing the use of borohydride and cofactors like NADH and NADPH. How do these reducing agents differ in terms of effectiveness and biological applicability? |
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Discuss the role of polar amino acids in protein structures. How does the environment's pH affect the polarity of amino acids like aspartate and glutamate? |
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Discuss the role of serendipity in drug development, using penicillin as an example. How can unexpected discoveries like this shape the field of medicine? |
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Discuss the significance of enterohepatic cycling in drug excretion. How does this process affect the metabolism and excretion of drugs in the body? Provide examples to support your discussion. |
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Discuss the significance of pH in the reaction of RNase A and how it affects the formation of intermediate molecules. |
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Discuss the significance of the catalytic triad in chymotrypsin and how its protonation affects enzymatic activity. Provide examples of inhibitors that target specific residues in the triad. |
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Discuss the significance of the catalytic triad in trypsin, chymotrypsin, and elastase, and how different amino acids in the active site influence substrate binding. _Provide examples of specific amino acids in each enzyme._ |
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Discuss the structural features of nuclease enzymes, including the 'cup' shaped active site and the conserved motifs found in homodimers. Explain how these features contribute to the specificity and function of nuclease enzymes. |
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Discuss the three parts of DNA polymerase I and their functions in DNA replication. How does the formation of a double helix impact entropy? |
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Examine the concept of receptor recycling and its impact on allosteric modulation. How does receptor recycling complicate the modulation process? Discuss the implications of receptor recycling in drug development and targeting specific receptors. |
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Examine the significance of metal ions in nuclease enzymes, particularly focusing on the coordination and positioning roles of metal ions in the cleavage of phosphodiester bonds. Compare the functions of different metal ions commonly used in nuclease mechanisms. |
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Explain the concept of competitive enzyme inhibition and how it affects the enzyme-substrate complex formation. Provide examples of competitive inhibitors and their impact on enzyme activity. |
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Explain the concept of competitive inhibition using the Michaelis-Menten curve. How does this type of inhibitor affect binding efficiency and the maximal rate of the reaction? Discuss the necessity of mutational analysis in identifying non-competitive inhibitors. |
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Explain the concept of drug screening and how it is utilized in the development of medications like aspirin and heroin. What are the advantages and limitations of this approach? |
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Explain the concept of drug selectivity and the importance of off-target binding in drug development. How does a low off-target Kd value contribute to the selectivity of a drug? |
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Explain the concept of general acid-base catalysis and provide examples of how it applies to the action of RNase A. |
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Explain the concept of ligand binding and the significance of the dissociation constant (Kd) in drug-target interactions. How does a lower Kd value indicate stronger interactions between a drug and its target? |
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Explain the concept of pseudo-first order conditions in kinetics. How does the approximation of [A] ≪ [B] simplify the rate equation? Discuss the implications of this simplification in experimental data analysis. |
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Explain the concept of specificity pockets in proteases and how they contribute to substrate recognition. Compare the specificity of TEV and thrombin, _providing examples of their specific cleavage sites_. |
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Explain the concept of therapeutic index in drug development. How is it calculated and why is it important in determining the safety and efficacy of a drug? Provide real-world examples to illustrate your points. |
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Explain the importance of choosing the right assay method based on sensitivity and availability when designing an experiment. |
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Explain the process of drug metabolism, including the roles of oxidation and conjugation. How does xenobiotic metabolism impact drug compounds? Provide a detailed analysis with examples. |
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Explain the process of surface plasmon resonance (SPR) and how it is used to determine drug binding relationships. Discuss its limitations in representing real-world binding interactions. |
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Explain the process of template-directed DNA synthesis catalysed by DNA polymerase. What are the different precursor molecules used in DNA replication? |
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Explain the role of a pH-stat in maintaining a constant pH during a reaction. How does it work, and why is it important in certain experiments? |
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Explain the role of metal ions in nuclease enzymes' mechanisms, focusing on how they assist in the cleavage of phosphodiester bonds. Provide specific examples of metal ions and their functions in this process. |
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Explain the role of specificity pockets in serine proteases like trypsin and subtilisin. How do these pockets contribute to substrate selectivity and enzyme function? |
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Explain the significance of the active site structure in high fidelity DNA polymerases and how it impacts replication fidelity. |
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Explain the significance of the conserved residues and structural similarities between E. coli ENR and B. napus ENR. How do these similarities impact their functionality? |
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Explain the significance of the quench flow apparatus in studying fast reactions in biochemical kinetics. How does it differ from traditional methods? Discuss the advantages and limitations of using this apparatus. |
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Explain the significance of the third metal ion in DNA polymerase activity and its potential impact on polymerase fidelity. How does the presence of this ion affect the stability of PPi during nucleotide incorporation? |
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Explain the structural changes in the nicotinamide ring of NAD(P)H during oxidation and reduction processes. How do these changes impact the efficiency of hydride transfer in enzymatic reactions? |
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Explore the mechanism of polymerase translocation in DNA Polymerase I and its role in nucleotide addition during replication. |
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Explore the process of error correction by the exonuclease domain of DNA polymerase. How does the polymerase recognize and remove incorrect nucleotides? Discuss the challenges associated with the distance between the synthetic and exonuclease domains. |
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Explore the role of peptide bonds in proteins. Why are peptide bonds considered planar, and how does the hybridization of Cα affect the flexibility of the peptide backbone? |
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Explore the significance of Lipinski’s ‘rule of 5’ in drug absorption. What are the key criteria outlined in this rule, and how do they influence the absorption of small molecule drugs? |
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Explore the significance of the release of PPi during nucleotide incorporation by DNA polymerase. How does the presence of Mg2+ ions aid in arranging DNA correctly during replication? |
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Explore the structural differences between subtilisin and chymotrypsin despite having the same catalytic triad arrangement. Discuss the implications of faults in threonine peptidases in cancers. |
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How does fluorine substitution next to an oxygen atom impact a drug's polarity and solubility in water? Discuss the implications of fluorine's effect on the distribution and bioavailability of the drug. |
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How does the presence of competitive inhibitors affect the Michaelis-Menten plots of enzyme-catalysed reactions? Explain the changes in Km and Vmax with increasing inhibitor concentrations. |
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Investigate the differences in the polymerase fidelity between DNA polymerases and the factors that influence error rates. How does the exonuclease domain contribute to maintaining the accuracy of DNA replication despite potential errors? |
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Investigate the impact of damaged bases on replication fidelity and the role of trans-lesion synthesis polymerases in overcoming this challenge. |
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Investigate the mechanism of action of bortezomib as a protease inhibitor, emphasizing its transition between trigonal and tetrahedral geometries. Explain why bortezomib is considered a suicide inhibitor. |
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Propose potential strategies for designing inhibitors targeting peptide deformylase (PDF) based on its mechanism of action. Discuss the importance of substrate mimics and non-hydrolysable molecules in inhibitor design for PDF. |
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Why is the incorporation of U (uracil) into DNA or T (thymine) into RNA uncommon during natural synthesis? Discuss the role of phosphodiester bonds in DNA structure. |
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