Some of the papers you were asked to read dealt with Cancer and Metabolism. Read

Question

Some of the papers you were asked to read dealt with Cancer and Metabolism. Read these carefully to put together answers/discussions of the following topics. Please download this list of questions to a Word document, then answer the specific questions in the correct sections. For example, part i asks you to discuss how the rate of glucose catabolism in cancer tissues compares to the rate of glucose catabolism in normal surrounding tissues? Answer that in that section. Then go on to answer part ii 1. Glycolysis in cancer cells. Address all parts including specific reactions, enzyme isoforms and specific examples of How does the rate of glucose catabolism in cancer tissues compare to the rate of glucose catabolism in normal surrounding tissues? (1 pt) i. [answer here] ii. What is the Warburg effect? What are reasons that it would be beneficial for cancer cells to have higher rates of glycolysis compared to normal surrounding tissues? Give at least three specific benefits and also include explanations (5 pts) [answer here] iii. What enzymes of glucose metabolism are expressed in higher levels in cancer tissues than normal tissues? What oncogenes have been as leading to the higher levels of expression of these glucose metabolizing enzymes? Give at least three specific examples and include explanations. If specific isoforms have been identified, associated with specific cancers, include that information. (5 pts) [answer here] iv. What would high rates of glycolysis and build-up of glycolytic intermediates have on the rates of pentose phosphate pathway in tumor cells Explain this based on what you know about regulation and effectors of the pentose phosphate pathway. Why would an elevated pentose phosphate pathway, increased products of the pentose phosphate pathway, be beneficial to cancer cells and why? (4 pts) [answer here] What glycolytic enzymes have been targeted for cancer diagnosis and/or chemotherapy? Give at least three specific examples and explanations of why targeting/inhibiting these enzymes would be expected to work and briefly explain what has been done/tried. (6 pts) v. [answer here] vi. Some of the first attempts at targeting glycolytic enzymes for cancer treatment have not been very successful. What are some other therapies associated with glucose metabolism that have been proposed? What is/are major problem(s) that would need to be overcome if inhibitors of glycolytic enzymes or transporters associated with glycolysis substrates or products are tested as chemotherapeutic agents? (4 pts) [answer here]

Explanation / Answer

Answer:

i. The rate of glucose catabolism in cancer tissues proceed about ten times faster than the rate of glucose catabolism in normal surrounding tissues.

ii. Warburg effect is also called aerobic glycolysis. It is a phenomenon in cancer cells characterized by increased uptake of glucose and exhibit anaerobic breakdown of glucose despite in presence of ample oxygen, to produce extensive amounts of their energy.

Higher rate of glycolysis is beneficial as compared to normal tissues because of the following reason:

iii. Hexokinase, lactate dehydrogenase, pyruvate kinase 1 and PKM2 is an isoform of normal pyruvate kinase and rest enzymes of glycolysis are expressed highly in cancer cells in comparision to normal cells. c Myc oncogene.

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