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Transcript
1. 2. 3. 4. 5. 6. 7. 8. 9. Biochemistry Chapter 31 What intermediate of glycolysis is used to make triacylglycerols? a. Glyceraldehyde 3-phosphate (G3P) What three steps of gluconeogenisis differ from glycolysis? a. Conversion of pyruvate to phoshpoenol pyruvate (series of enzymes), of fructose 1,6 bisphosphate to fructose 6 phosphate (1 enzyme), and the conversion of glucose 6 phosphate to glucose (1 enzyme) What are some ways that hypoglycemic coma and hyperglycemic coma presentation differs? a. Hypoglycemic patients often have wet, flushed skin because they are not dehydrated (from high glucose in blood); b. Hyperglycemic coma patients have dry, pale skin, acetone on breath (sweet smell), dehydration, kussmal breathing, low blood pressure, and rapid heartbeat. When are blood glucose levels considered unequivocally elevated? If fasting glucose is between 111 and 140 mg/dL, what is the diagnosis? What further testing can be done? a. Unequivocally elevated glucose levels are > 200mg/dL regardless of last food consumption. b. 111-140 mg/dL is considered Impaired fasting Glucose Tolerance (IGT). If in this range an oral glucose tolerance test (OGTT) can be done where a patient fasts overnight and then is give 75 g of glucose. Levels are measured before the glucose and in 30 min intervals after. If the blood glucose level is EVER above 200mg/dL diabetes mellitus is indicated What are the three sources of carbon that can be used in gluconeogenisis? What cannot be used as a source? a. Glycerol, amino acids (esp. alanine), and lactate; Ethanol CANNOT be used Why does dexamethasone cause muscle weakness is emma weezer? a. Because it mobilized her amino acids out of her muscle for use in gluconeogenisis How does lactate enter the gluconeogenisis cycle? Amino acids? Glycerol? a. Lactate is converted to pyruvate by NADH b. Some amino acids, like alanine, are converted to pyruvate; others are converted to TCA cycle intermediates; either can enter the cycle c. Glycerol form DHAP (dihydroxyacetone phosphate) and hence enter the cycle Can fatty acids be used for gluconeogenisis? a. FAs with an odd number of carbons can be used. The three carbons on the end of the chain form propionyl coA that can be used. The rest is converted to Acetyl coA and since pyruvate dehydrogenase is irreversible, isn’t used. How does alcohol metabolism block the production of gluconeogenisis precursors? a. The alcohol must be oxidized by NAD+ increasing the NADH/NAD+ ratio. Alanine, glycerol, and lactate all need NAD+ to enter gluconeogenisis, and when levels of NADH are high pyruvate generated in any way is made into lactate. 10. How is pyruvate converted to phosphoenolpyruvate? a. Pyruvate is first converted into oxaloacetate by pyruvate carboxylase. Other intermediates of the TCA cycle can also be converted to oxaloacetate, so they enter the cycle here. Oxaloacetate cannot cross the mitochondrial membrane so is converted into one of three things that can: PEP (by mitochondrial phosphoenolpyruvate carboxykinase, PEPCK), malate (uses NADH), or aspartate. Whether malate or aspartate is used depends on the need for reducing equivalents in the cytoplasm b. Once across the membrane malate and aspartate are reconverted to oxaloacetate by the reverse rxn and then it is converted to PEP by cystosolic PEPCK. 11. What vitamin is required as a cofactor for pyruvate carboxylase? a. Biotin (B7) 12. What enzyme converts fructose 1,6 bisphosphate to fructose 6-phosphate? How about glucose 6-phosphate to glucose? Both release Pi a. Fructose 1,6-bisphophatase; glucose 6-phosphatase 13. How do glucocorticoids stimulate gluconeogenisis via PEPCK? a. The increase the levels of it synthesized 14. How are the enzymes involved in the conversion of pyruvate to phosphoenol pyruvate regulated in gluconeogensis? a. In fasting state, FAs undergo β-oxidation to produce acetyl CoA, ATP, & NADH. This causes conc. of ADP to decrease resulting in phosphorylation of pyruvate dehydrogenase inactivating it. Ultimately, this prevents pyruvate from being converted to Acetyl CoA. b. Increased Acetyl CoA levels form FA oxidation activate pyruvate carboxylase, so increase conversion of pyruvate to oxaloacetate. c. Cytosolic PEPCK is inducible, so when cAMP increases (via glucagon in fasting, epinephrine in stress/exercise, or cortisol) it actives protein kinase A which phosphorlyates CREB transcription factors increasing production of PEPCK d. Increased cAMP leads to phosphorylation and hence inactivation of pyruvate kinase 15. How do levels of fructose 2,6 bisphosphate and AMP impact whether glycolysis or gluconeogenisis occur? a. When levels are high they allostericly inhibit fructose 1,6 bisphosphatase and activate phoshphofructokinase-1, both of which favor glycolysis. When levels are low, the allosteric inhibition is low and PFK-1 activity is low, favoring gluconeogenisis. 16. How is glucokinase activity regulated by glucose levels? a. It has a high Km (so low affinity) for glucose, so when levels are low in the blood it is mostly inactive; when glucose levels are high it’s velocity increases 17. How does insulin facilitate glycogen production in the liver? a. Activates glycogen synthase and inactivates glycogen phosphorylase 18. Why does Di Abietes develop a coma when she accidently injects too much insulin a. The insulin decreased her blood glucose by causing glucose to be distributed in the tissues, and at the same time blocked gluconeogensis so she could not get glucose out of the tissue and into her blood to prevent the coma.32 19. Why is muscle glycogen not used to maintain blood glucose levels? a. Muscle lacks glucose 6-phosphatase, so glucose can’t be produced from glucose-6 phosphate for export 20. How does the nonenzymatic glycation of proteins suggest microvascular and macrovascular complications of diabetes arise? a. At chronic elevated levels of glucose, glucose forms covalent bonds with proteins (glycosylation) and over time these glycosylated proteins form cross links narrowing the vascular lumen.