Objectives

Learning Objectives 1

Glycolysis

1. Draw the chemical structures of the substrates and products of the glycolytic pathway.

2. Identify the enzymes of glycolysis that catalyze steps in which ATP is used or formed, and in which NADH is formed.

3. Compare the stoichiometry of energy production in anaerobic vs, aerobic glycolysis.

4. Describe the hepatic fructose and galactose pathways and identify their metabolic endproduct that is an intermediate of glycolysis.

Citric Acid Cycle

1. For E1, E2 and E3 of the pyruvate dehydrogenase complex list their substrates and products, identify their co-factors giving the roles and vitamin sources, and discuss their regulation.

2 Draw structures for the substrates and products in the citric acid (tricarboxylic acid) cycle, pay particular attention to the reactions associated with energy production (GTP, NADH, FADH₂ formation) and describe their regulation.

3. Discuss the energy production from the citric acid cycle.

Gluconeogenesis / Pentose Phosphate Pathway

1. Describe how the oxidative and non-oxidative branches of the pentose phosphate pathway affect glycolysis.

4. Draw structures for the gluconeogenic precursors and products identify the enzymes that differ from those of glycolysis.

5. Describe the Cori and glucose-alanine cycles, and their relationship to gluconeogenesis.

Glycogen and Integration

1. Describe the general structural features of glycogen.

2. List the general features of the steps in glycogenolysis (degradation) and glycogenesis (synthesis).

3. Integrate glycolysis, the PDH complex, citric acid cycle, pentose phosphate pathway, gluconeogenesis, glycogen, the urea cycle and amino acid metabolism.

Allosteric Regulation

1. Review the role of adenylate kinase in regulation.

2. Compare the kinetic characteristics of glucokinase and hexokinase, and discuss their regulation.

3. Describe how phosphofructokinase and pyruvate kinase are regulated allosterically.

4. Identify the key aspects in pyruvate carboxylase regulation.

5. Describe the coordinated allosteric regulation of glucose metabolism, especially in terms of cell energy levels, blood glucose conditions and relative amounts of glucose-6- phosphate.

Insulin and Glucagon

1. Compare and contrast the structures of preproinsulin, proinsulin and insulin.

2. Describe the six steps associated with the synthesis of preproinsulin and its conversion to proinsulin and the sequence of events from transcription to exocytosis.

3. List the order of events in pancreatic processing of preproglucagon.

4. List the major metabolic effects of insulin and glucagon in liver, muscle and adipose cells.

5. Identify the general structural features of the insulin receptor.

6. Discuss the relationship of interchain autophosphorylation of tyrosine residues in the insulin receptor to intracellular insulin action.

Case Study

1. Describe the biochemistry of insulin-dependent diabetes mellitus (IDDM) and explain why the disease might not appear until after a viral infection.

2. Explain why glycosylated hemoglobin levels (AGE's)can be elevated in insulin-dependent diabetes mellitus.

Be able to trace a single carbon atom through glycolysis and the citric acid cycle. Practice, start with glucose, keep track of carbons 1 through 6 all the way through glycolysis, the PDH complex and the citric acid cycle.