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Download Problem set #3 Answers 1. The 3 main links between lipid synthesis
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Problem set #3 Answers 1. The 3 main links between lipid synthesis and carbon skeleton of metabolism are: Pathway glycolysis Intermediate DHAP Lipid pathways triglycerides phosphoglycer. Function provides glycerol backbone ________________________________________________ TCA cycle citrate (acetyl CoA) fatty acid syn substrate cholesterol substrate ________________________________________________ Pentose NADP:H fatty acid syn. reducing power shunt cholesterol syn. reducing power ________________________________________________ 2. Explain how lipids are digested, absorbed and transported in the human body. Please see notes from file: pentfa.pdf. 3. Besides the information below, the information from summary chart on these two paths should be added to the chart below. fatty acid synthesis β oxidation Location of paths in cells cytoplasm mitochondrial matrix ________________________________________________ cofactors used in NADP:H FAD, NAD+ oxidation/reduction reactions ________________________________________________ hormonal control, if any glucagon inhibits not known insulin stimulates not known ________________________________________________ 4. Please see notes on membranes and phosphoglycerides. 5. Compare gluconeogenesis pathway to fatty acid synthesis pathway. fatty acid synthesis gluconeogenesis Location of paths in cells cytoplasm I mitochondrial matrix II. cytoplasm ________________________________________________ main function storage of acetyl formation of glucose units for future from non-CHO sources ________________________________________________ regulation citrate stimulates - acetyl CoA stimulates acetyl CoA pyruvate carboxylase carboxylase - ATP stimulates diphosphofructo-phos. ________________________________________________ rate-limiting step acetyl CoA pyruvate carboxylase catalyzed by carboxylase ______________________________________________________ hormonal control, if any glucagon indirectly inhibits acetyl CoA carboxyl. __________________________________ insulin indirectly stimulates citrate lyase ______________________________________________________ 6. a. Describe how insulin acts to alter the metabolism of lipids and carbohydrates in human cells. Insulin is a protein hormone that never enters the target cell. Insulin binds to its receptor protein on skeletal muscle cell membranes and liver cell membranes and initiates the cascade that results in irs-1 formation. irs-1 is the second messenger for Insulin. irs-1 stimulates the transport of glucose into the target cells and thereby decreases the [glucose] in the blood stream. irs-1 also stimulates acetyl CoA carboxylase and therefore fatty acid synthesis. It also stimulates phosphodiesterase which degrades cAMP. Less cAMP prevents the inactivation of HMG CoA reductase allowing more cholesterol to be formed. b. Explain the difference between type I and type II diabetes. Type I diabetes appears to be the result of an autoimmune destruction of the pancreatic cells that form and secrete insulin. The lack of insulin results in decreased uptake of glucose by skeletal muscle cells leaving most of the glucose ingested still in the blood stream. Individuals with this form of diabetes generally acquire it between the ages of 10 and 30, so it is often called juvenile diabetes. Type II diabetes is often called late onset diabetes and occurs when skeletal muscle cells reduce severely the number of insulin receptor protein molecules made. This lack of insulin receptors prevents insulin binding and therefore stimulation of glucose uptake, leaving lots of glucose in the blood stream. 7. Compare the degradation of glycogen in liver to the degradation of triglycerides in adipose tissue. see notes gng-glyc.pdf file for regulation of glycogen degradation 470mobil.pdf for regulation of triglyceride degradation 8. Please see the files cholsyn.pdf and steroid.pdf 9. Show a plausible pathway to label the following compounds with C14 assuming human cells are fed C14 labelled pyruvate. Indicate only key intermediates, and show the steps required to cross membranes. a. pyr ---> acetyl CoA-->citrate--> ||cytopl. citrate-->c. acetyl CoA --> malonylCoA -->palmitate b. pyr--->OAA-->malate ||-->OAA-->PEP-->-->-->f-i,6-bisP-->f-6-P-->g-6-P-->glycogen c. pyr ---> acetyl CoA-->citrate--> ||cytopl. citrate-->c. acetyl CoA --> malonylCoA ->-->palmitate -->lecithin OR c. pyr--->OAA-->malate ||-->OAA-->PEP-->-->- 3PG--> DHAP --> glycerol-P --> phosphatidate-->lecithin d. pyr ---> acetyl CoA-->citrate--> ||cytopl. citrate-->c. acetyl CoA-->-->HMG CoA-->-->cholesterol e. pyr ---> acetyl CoA-->citrate--> ||cytopl. citrate-->c. acetyl CoA--> malonylCoA -->-->palmitate -->stearate-->oleic acid f. pyr ---> acetyl CoA-->citrate--> ||cytopl. citrate-->c. acetyl CoA--> malonylCoA -->-->palmitate -->stearate-->tristearate OR pyr--->OAA-->malate ||-->OAA-->PEP-->-->- 3PG--> DHAP --> glycerol-P --> phosphatidate-->tristearate 10. Compare the mechanism of action of the protein hormones, glucagon and insulin to the steroid hormones, estrogen and vitamin D. Details should be found in the notes. NOTE that glucagon and insulin never enter cells but cause changes through a second messenger. All steroid hormones enter cells and together with specific receptor proteins bind to DNA and influence expression of specific genes. 11. Please go through the animation, Vitamin D on your CD-ROM.