(8/24/10) - Introduction to Metabolic Pathways

Glycolysis: 1.  Outline the sequence of reactions in aerobic and anaerobic glycolysis. Mark on the pathway the regulatory enzymes.

2.  Summarize the energetics of aerobic and anaerobic glycolysis by highlighting the reactions involved in the utilization and generation of ATP, and the net yield of ATP during glycolysis (include those reactions that generate NADH).

3.  Notate the net reaction for the conversion of glucose into pyruvate and the number of ATP and NADH molecules formed.

4.  Identify the major regulatory step of glycolysis and describe in detail the mechanism(s) of regulation of the enzyme(s) involved with particular reference to the production or conversion of 2,6-bisphosphate. Compare and contrast the regulatory events in the fed vs. fasting states.

5.  Identify the step(s) in glycolysis:

A.  That illustrate the use of coupled reactions to drive thermodynamically unfavored processes including substrate level phosphorylation.

B.  That exhibit feed-forward regulation.

C.  Whose product can be diverted to produce an important regulator of oxygen binding to hemoglobin. Note the physical characteristics of this molecule and understand how these enable the molecule to perform its function.

D.  That have clinical significance, including the most common genetic deficiencies and their consequences.

6.  List the functional differences between hexokinase and glucokinase and identify when they are operational during the feed-fast cycle. Explain how this occurs i.e. how are they regulated. Understand why phosphorylation is an important first step in the glycolytic pathway.

7.  Explain why glycolysis is essential for normal RBC functions including consequences in deficiencies in glycolytic enzymes and the role of glycolysis in adaption to high altitude.

8.  Describe how flux down or up the pathway is coordinated by hormonal regulation.

9.  Describe the role of lactate production and the clinical significance of lactic acidosis.

10. Review the uptake of glucose into cells.

TCA: 1.  Outline the sequence of reactions in the TCA cycle and mark on the pathway the enzymes involved and which steps of the cycle yield CO2, NADH, FADH2 and GTP.

2.  Identify the metabolic sources of the two intermediates required in the first step of the TCA cycle.

3.  List major metabolic intermediates synthesized from TCA cycle intermediates (add these to the diagram in #1).

4.  Describe briefly how the TCA cycle is regulated by substrate supply, allosteric effectors, covalent modification and protein synthesis.

5.  List 4 common fates for the molecule pyruvate.

6.  Explain why there is no synthesis of glucose from acetyl CoA, and know the fate of acetyl CoA. Understand the regulation of acetyl CoA production and why it is important.

7.  Calculate the yield of ATP from the complete oxidation of glucose, pyruvate and acetyl CoA.

8.  Describe which intermediates accumulate during beri-beri deficiency and why.

9.  Describe what is meant by “insulin resistance” with regards to GLUT-4 receptors and diabetes.

10. Know where the TCA cycle takes place, and why this location is important for linking it to energy production.