Molecule A held promise as a treatment for rheumatoid arthritis except that it remained in the body for too long (~120 hours in rat models). Suggest a minor modification you could make to increase the rate at which it might be metabolized and therefore excreted by the body. [If you can solve this problem, you will have invented the drug Celebrex®.] Cl. O=S= H₂N O A -CF3 Celebrex
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- Figure 1 shows the catalytic triad of a-chymotrypsin. Identify A, B and C. Describe the subsequent steps of stage 1 and stage 2 of a- chymotrypsin mechanism. Illustrate with diagrams. A B CH2 H-N N: H-O Figure 1Acetazolamide is a drug which inhibits carbonic anhydrase. Carbonic anhydrase participates in regulation of the pH and bicarbonate content of a number of body fluids. Figure 2 shows the experimental curve of initial reaction velocity (as percentage of Vma) versus [S] (concentration) for the carbonic anhydrase reaction. The graph also shows the curve in the presence of acetazolamide. 100 No inhibitor 50 Acetazolamide 0.2 0.4 0.6 0.8 [S] (mM) Figure 2 (i) Compare the maximal velocities and Michaelis Menten constants of the enzyme in the absence and the presence of the inhibitor acetazolamide. Determine the nature of inhibition by acetazolamide. Explain your answer. (ii) Name TWO (2) other types of inhibitions besides the inhibition shown by acetazolamide. Sketch a graph of V versus [S] showing curves in the absence of an inhibitor and in the presence of the types of inhibitors not shown by acetazolamide. ("AJO %) AThis is a visible spectra between 390-590 nm obtained during the protein separation process of haemoglobin and cytochrome c using CM Sephadex chromatography. I'd like the results shown on the image interpreted. Look for characteristic peaks or patterns that correspond to the absorption properties of these proteins in the visible range.
- A researcher wants to look for glucaronic acid conjugated metabolites in sample of urine(glucaronic acid conjugation is a common method of metabolism for excretion.) Pronotated glucaronic acid conjugated metabolite ions often lose anhydroglucaronic acid(176 Da) during low energy CID. Which triple quadrupole experiment might be best for finding these conjugates?Drug X has the following properties: Multiple H bond donors and acceptors, a low log P, a low solubility in octan-1-ol, low molecular weight and contains both amino and carboxylic acid functional groups. Which of the following statements about the predicted oral bioavailability is TRUE? A. The drug will likely utilise the passive transcellular pathway. B. The drug will probably display increased oral bioavailability when taken after a high fat meal C. The drug resembles an amino acid and could be absorbed by the folate transporter D. The low logP suggests extensive partitioning into the phospholipid bilayer of the small intestinal mucosa E. The drug could be absorbed by the amino acid transporters expressed in the small intestineAcetazolamide is a drug which inhibits carbonic anhydrase. Carbonic anhydrase participates in regulation of the pH and bicarbonate content of a number of body fluids. Figure 2 shows the experimental curve of initial reaction velocity (as percentage of Vmax) versus [S] (concentration) for the carbonic anhydrase reaction. The graph also shows the curve in the presence of acetazolamide. 100 No inhibitor 50 Acetazolamide 0.2 0.4 0.6 0.8 (S] (mM) Figure 2 (i) Compare the maximal velocities and Michaelis Menten constants of the enzyme in the absence and the presence of the inhibitor acetazolamide. Determine the nature of inhibition by acetazolamide. Explain your answer. (*"A JO %) A
- Carbonic anhydrase catalyzes the hydration of CO. CO2 + H2O ¬ H½CO3 The Km of this enzyme for CO, is 1.20×104 µ.M. When [CO,] = 3.60×104 µM, the rate of reaction was 4.50 umol·mL! sec-1 a What is Vmax for this enzyme? umol·mL-!sec-!Pharmaceuticals When a medicine is administered orally, the concentration of the drug in the patient's circulation after t minutes is given by C(t) = 0.06t – 0.00021, where Osls 240 and the concentration is measured in mg/L. When does the highest serum concentration occur, and what is that maximum serum concentration?Angiotensin Converting Enzyme (ACE) inhibitors cause blood vessels to relax, thereby reducing blood pressure. Although Captopril is part of the group of antihypertensive drugs widely used as ACE inhibitors, new research is constantly being carried out with the aim of selecting compounds that are more kinetically advantageous than Captopril. Therefore, a BioPharma employee selected some prototypes and performed kinetic tests, finding the result shown in the figure below. Based on the statement and the graphic above, mark the incorrect alternative. A) It is a graph for determining kinetic parameters according to Lineweaver-Burk. In that case, the coefficient a B) Comparing the prototypes with the reference drug, Prototype 1 has a higher Vmax value. C) Comparing the prototypes with the reference drug, Prototype 2 has a lower Vmax value. D) Captopril has a Vmax of approximately 0.730 and Km of approximately 0.669. E) The two prototypes have Km values lower than those of Captopril and,…
- We want to measure the activity of alanine aminotransferase (ALAT) present in a serum. The reaction catalyzed by the enzyme is: Reaction 1: +H3N- glutamate H C CH₂ CH₂ COO -COO + pyruvate CH3 C=0 0.1 M phosphate buffer pH 7.4 : 550 µL 1.2 M alanine : 100 μL CH3 time (min) A340 COO COO™ pyruvate lactate dehydrogenase* (LDH, 300 µg.mL-¹): 50 μL 1.5 mM NADH: 200 μL 0.04 M a-ketoglutarate: 500 μL serum containing ALAT: 600 μL The enzyme reaction is realized in the following conditions: In a 1 cm-cuvette are added: 0 0.915 ALAT NADH + H+ LDH a-cétoglutarate COO * Lactate dehydrogenase (LDH) reduces pyruvate into lactate, with the concomitant oxydation of NADH. This allows to indirectly measure the amount of product formed. Reaction 2: NAD+ 1 0.741 C=O H CH₂ CH₂ COO™ CH3 C-OH COO lactate The reaction is performed at 25 °C and the absorbance at 340 nm is monitored every minute, for 5 min. The absorbance values are given in the table below: Data: alanine ENADH at 340 nm = 6220 M¹.cm1. One…Chymotrypsin is an enzyme that is optimized to function in the small intestine (at a pH of ~7.4). Explain, given what you know about the chymotrypsin mechanism and what we learned about acid/base chemistry, why chymotrypsin would not be able to initiate catalysis if it were secreted into the stomach (pH ~2.5).On the right the Hill plot com- (b) pares the O2 binding properties of Hb Ya- kima with those of HbA in 0.1 M NaCl buff- Hb-Yakima ered to pH 7 with 0.01 M bis-Tris. Focus first on the line for "stripped Hb". This is the term for hemoglobin isolated from erythro- cytes with removal of all organic phosphate molecules that might bind to the protein in RBCS. You can see that 2,3-bisphospho- glycerate (BPG; labeled DPG according to old terminology) does not alter the O2 bind- ing affinity of Hb Yakima in contrast to HbA (although it was shown that BPG did bind to the deoxyHb Yakima molecule). Also, Hb Yakima is associated with markedly decreased allostery in the absence and presence of BPG, in comparison to HbA. IHP = inositol hexaphosphate, an artificial allosteric modifying ligand that binds more tightly than BPG. stripped Hb Hb-A •DPG +DPG n= 1.0 n = 2.3 n=2,5 +THP +IHP 0.5 0.5 1 5 10 50 po, ( mm Hg ) %3D On the right is a diagram copied from the lecture handout "Hemoglobin and Allo-…