ChemE 355: Biological Frameworks for Engineers Handed out on 11-15-04; due on 11-23-04

Take-home exam #2

Work on this on your own; do not discuss it with other members of the class. You can use any web or printed resources to help, and you can ask Greg () for clarification help. This exam is due on Tuesday, November 23rd at 2:30 PM (in lab); you may turn in your answers early at Wilcox 272 or in lab on Monday if it is not convenient for you to come to lab at 2:30 on Tuesday.

Question 1: Contraction of muscle cells

1A. Draw a graph of a length-tension curve for a typical vertebrate muscle. Plot sarcomere length on the X axis and tension on the Y axis. Give actual numbers when possible.

1B. What is a sarcomere? At what sarcomere length(s) is maximal force produced by the muscle? Explain why, referring to the relationship between sarcomere length and the arrangement of actin and myosin filaments.

1C. The ATP used by exercising muscle cells includes ATP used by myosin/actin interactions plus ATP used by all other processes, including Ca2+ pumping. A scientist reasons that if she can estimate the rate of ATP use in muscles that are stretched out to the point where actin and myosin do not overlap, that estimate should be the rate of ATP use by all other processes (which are independent of length). She does several careful experiments on isolated contracting frog muscles and obtains the following data.

Based on these data, when muscle cells are at their optimal sarcomere length and are exerting maximal force, what fraction of total ATP use is not due to myosin/actin interactions? Explain your reasoning.

1D. Based on this graph and your knowledge of muscle cell physiology, what would you expect the total rate of ATP use to be at a sarcomere length of 1.5 um?

1E. The scientist next decides to do a comparison of frog muscles and rattlesnake tailshaker muscles. Using the same protocol as before, she obtains the following data for the rattlesnake tailshaker muscles.

Assuming that normal sarcomere length ranges are similar for rattlesnake tailshaker muscles and frog muscles, how does the partitioning of ATP use differ between frog muscles and rattlesnake tailshaker muscles? Given what you know about the composition and function of rattlesnake tailshaker muscle cells, is this surprising? Why or why not?

1F. In all of the above experiments, electrical stimulation was used to prompt the muscles to contract. In reviewing her protocol, the scientist realizes that the stimulation she used may not have been strong enough to recruit all the motor units in the muscle. Does this affect the validity of your answer to question 1C? Why or why not?

Question 2: Glycolysis in reverse

In class we discussed the metabolic pathway of glycolysis, in which glucose is broken down into pyruvate. Loosely speaking, the “opposite” of glycolysis is a pathway called gluconeogenesis, in which pyruvate is made into glucose. A diagram of the pathway (copied from is shown below.

2A. Write a balanced chemical equation showing the overall stoichiometry of this pathway.

2B. Do two pyruvate molecules contain more or less chemical bond energy than one molecule of glucose? How do you know? (“Because a website says so” is not a valid response.)

2C. Does gluconeogenesis use any of the same enzymes as glycolysis? If so, which ones?

2D. Obviously, it would make little sense for high rates of glycolysis and gluconeogenesis to occur simultaneously. Under what physiological conditions (e.g., high blood [glucose], exercise, flight-or-fight stress, etc.) should liver cells carry out glycolysis and under what conditions should they carry out gluconeogenesis? Please justify your answer. According to how are the two pathways controlled in such a way that only one of them is active at a time?

2E. In class, we discussed the figure shown below (titled “The response by a liver cell to glucagon or epinephrine” and taken from G. Karp, Cell and Molecular Biology, 2002). The figure shows that hormones such as glucagon and epinephrine cause changes in gene expression. How do changes in gene expression specifically increase the rate of gluconeogenesis in liver cells?

2F. As shown in this figure, changes in gene expression are achieved through a long cascade of reactions initiated by a hormone. A simpler alternative design would be to have the hormone’s receptor directly mediate the effects of the hormone, without all of the intermediate steps. Give two advantages of controlling gene expression via a multistep cascade.

2G. As shown is the figure, the enzyme phosphodiesterase breaks cAMP down into AMP. Consider the case of a person with a mutation in their phosphodiesterease gene which impairs the catalytic ability of the enzyme phosphodiesterase. Would you expect this person to have higher-than-normal or lower-than-normal levels of blood [glucose]? Explain.

2H. Muscles are essentially incapable of gluconeogenesis, so they cannot make their own glucose. How do they obtain glucose? Be as specific and detailed as possible.

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