Metabolic map and bioactivation of the anti-tumour drug noscapine

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/
  1. Your assigned mutant for this question is VA from the Richards et al. article. Answer the following

a. What actual amino acids are different in this mutant compared to wild-type P450BM-3? What are some of
the known roles (in wild-type P450BM-3) of the changed amino acids?
b. What are the major products produced by the mutant when it is given noscapine as a substrate? (Hint:
Find the ‘supplementary material’ for the article for the best data.)
c. What is its ‘coupling efficiency’. What does this mean? How did the authors measure it?
d. What is the paper’s overall goal for the study, and does this mutant achieve their goal? Is it the best
mutant at achieving their goal?
e. Which of the human P450s tested in the Fang et al. paper is the VA mutant most like in terms of products
that it forms?

  1. In the Fang et al. article, they use a ‘dual-activity’ incubation system.
    a. What are the two activities, and why are both parts required to get the desired products?
    b. For UGT1A1, which glucuronide metabolites (C1, C3, or C4) was it capable of producing?
    c. In figure 6 panel A, it is shown that the products formed in the presence of NADPH but not GSH are
    different than those formed from the presence of both, and that the products formed in the presence of GSH
    but not NADPH are different that either of the other two sets of products. What does all of this tell us about
    the pathway generating the metabolites?
    d. Stare in awe at Figure 8 in all its glory. What is the difference between structure I and structure X? How
    do compounds VIII and IX relate to each other?

Sample Solution

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Program Notes

Write your own program notes about the piece you’re studying. Imagine that you have just started your own
concert series. You yourself are tasked with writing them for the concert booklet. Do some research on the
composition you’re playing. Give the audience some background about the composer, if necessary, and the
circumstances around the piece’s composition. You might want to mention interesting details about the
premiere (Did the audience riot?), first performers (Did an important musician commission the music?), or
the form of the piece (Is it in 7 movements played without pause? Does the first theme come back in the
last movement in a major key? Is the opening a 5-bar phrase?)

Sample Solution

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Capitalism, class inequality and Race

  1. Choose one of these social problems (racial profiling, police shootings, mass incarceration, drugs, gun
    violence, global capitalist system, extreme poverty, unemployment, low-wage jobs, inequality in education,
    the wage gap,racism, etc )
  2. Gather information. Make some observations. Look at social research data.
  3. Analyze the problem. Choose three or four examples from your observations and data to analyze. First,
    analyze how the problem is defined. Second, analyze how social structures or conditions in society create
    the problem. How does the definition of the problem reflect and reinforce the social structure (e.g., class,
    race, ethnicity, gender, sexuality, disability, global inequality, immigrant status, age)?
    What is the system that shapes the problem? (e.g. capitalism, class inequality, race or white supremacy,
    colonialism, neocolonialism, gender or patriarchy, homophobia or heterosexism, disability or ableism)?
    4.Write the description of the problems and research methods. Describe your topic and research methods,
    including observations, data and sources used.

Sample Solution

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Racial profiling, police shootings and mass incarceration

  1. Choose one of these social problems (racial profiling, police shootings, mass incarceration, drugs, gun
    violence, global capitalist system, extreme poverty, unemployment, low-wage jobs, inequality in education,
    the wage gap,racism, etc )
  2. Gather information. Make some observations. Look at social research data.
  3. Analyze the problem. Choose three or four examples from your observations and data to analyze. First,
    analyze how the problem is defined. Second, analyze how social structures or conditions in society create
    the problem. How does the definition of the problem reflect and reinforce the social structure (e.g., class,
    race, ethnicity, gender, sexuality, disability, global inequality, immigrant status, age)?
    What is the system that shapes the problem? (e.g. capitalism, class inequality, race or white supremacy,
    colonialism, neocolonialism, gender or patriarchy, homophobia or heterosexism, disability or ableism)?
    4.Write the description of the problems and research methods. Describe your topic and research methods,
    including observations, data and sources used.

Sample Solution

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