Chapter 15 Answers
Glycogen Metabolism and Gluconeogenesis
Book study exercises 4,5 and 8
4 – Opposing metabolic pathways must differ in at least one step because each process must be exergonic. This means that an exergonic step of the degradative pathway cannot simply operate in reverse for the biosynthetic pathway (for which this would be an endergonic step) but must be bypassed by another, exergonic reaction. For example, in glycogen degradation. This step is bypassed by linking the glucose nucleotide (UDP-Glucose), which can then serve as a substrate for glycogen synthase. These two steps are exergonic.
5 – In a simple allosteric system the activity of each enzyme in a metabolic pathway varies in response to the presence of allosteric activators and inhibitors. These compounds bind to the enzyme in a stoichiometric fashion, so their concentrations must remain constant for their effects on the enzyme to persist. A phosphorylation/dephosphorylation system allows more sensitive regulation of a pathway for two reasons. First it can operate in addition to allosteric effects, which permits a greater range of regulatory responses. Second phosphorylation and dephosphorylation, which resut from a hormonal or neuronal signal, can be amplified or dampened in a catalytic fashion. Thus the state of phosphorylation of an enzyme does not require a constant stoichiometric concentration of another substance (section 15-3)
8 – Oxaloacetate, the product of the pyruvate carboxylase reacton is produced in the mito. Depending on the species, OAA may be converted to PEP in the mito or the cytosol, and the remaining gluconeogenic reactions occur in the sytosol (other than G6Pase). In species with cytosolic PEPCK mitochondrial OAA must be converted to malate or aspartate, both of which have specific mitochondrial transporters. In the cytosol, the malate or aspartate is converted back to OAA. When the malate shuttle is used, NADH is oxidized in the mitochondrion and NAD+ is reduced in the cytosol. The net result is the transfer of a reducing equivalent from the mitoshondrion to the cytosol. Thus, the malate shuttle supplies the cytosolic NADH required for gluconeogenesis (in the glyceraldehyde-3-phosphate dehydrogenase reaction). If gluconeogenesis begins with lactate rather thanpyruvate, its oxidation to pyruvate generates the required NADH so that the aspartate shuttle to transport oxaloacetate from the mito to the cytosol.
Chapter questions:
1) An increase in cAMP will likely lead to:
For each of the following answer as T/F
2) Glycogen is stored in muscle and liver T
3) Glycogen is a major source of stored energy in brain F
4) Glycogen fills the nucleus of the cells that store glycogen F
5) Glycogen storage occurs in the form of dense granules in the cytosol of cells T
6) Why is it important to have different pathways for glycogenesis and glycogenolysis in liver and muscle cells?
The separate pathways for the synthesis and degradation of glycogen allow the synthesis of glycogen to proceed despite a high ratio of Pi to glucose 1 phosphate. The separate pathways allow the coordinated reciprocal control of glycogen synthesis and degradation by hormonal regulation.
7) Which of the following statements about hormonal regulation of glycogen synthesis and degradation are correct?
9) Write out each of the 3 steps that differ between glycolysis and gluconeogenesis.
- the reaction catalyzed by PK is reversed by PC and PEPCK
- the reaction catalyzed by PFK is reversed by F 1,6-Bpase
- the reaction catalyzed by HK and GK is reversed by G 6Pase
See the book for the molecular structures
10) Pyruvate carboxylase adds a CO2 at the cost of 1 ATP, yet the same CO2 is removed later. Why? What is the product of this reaction.
The carboxylation reaction produces an activated carboxyl group in the form of a high energy carboxybiotin intermediate. The cleavage of the bond and release of CO2 in the PEPCK reaction or the transfer of electrons of the CO2 to acceptors in other reactions allows this endergonic reaction to proceed. Thus the formation of PEP form OAA is driven by release of CO2 and the hydrolysis of GTP
11) Describe the conversion of lactate to PEP. Why not just convert lactate to pyruvate and then reverse the reaction as in the paired reactions of fructose 1,6 bisphosphatase and phosphofructokinase? (hint see the last answer)
In the conversion of Fructose 1 phosphate to fructose 1,6 bisphosphate energy is and lost in the form of ATP hydrolysis or the hydrolysis of the phosphoryl group of the sugar moiety. The conversion of PEP to pyruvate includes and additional spontaneous step: the enol-ketol conversion. This precludes a reversal of the PK reaction. The thermodynamics are much more favorable for the conversion of OAA to PEP than pyruvate to PEP. A ÆGo’ difference of 7.3 kcal/mole.
12) the presence of epinephrine results in the stimulation of PFK-2 in heart muscle. How does epi affect glycolysis in this organ? Epinephrine dependent stimulation of PFK-2 leads to an increse in [F2,6P] which activates PFK-1. There is NO F16Pase in muscle so the result is an significant increase in glycolysis and an increrase in ATP formation.
13) How many high energy bonds are required to convert oxaloacetate to glucose?
14) Biotin is a carrier of
15) Fructose 2,6-bisphosphate is a potent activator of the liver phosphofructokinase and a potent inhibitor of the fructose 2,6-bisphosphatase enzyme. Fructose 2,6-bisphosphate is produced and metabolized by the same bifunctional enzyme phosphofructo kinase 2 (PFK2).
Under these conditions, gluconeogenesis is sufficiently rapid to meet cellular demand. Explain.
Short answer - The increase in PKA activity will lead to the increase in PFK2 in the phosphorylated state. This will cause the flux of carbons will be towards glucose due to the inhibition of glycolysis at PFK and the activation of gluconeogenesis at fructose 2,6-bPase.
16) Which of the following statements correctly describe what happens when acetyl CoA is abundant?
17) Explain how the enzymatic activity of phosphoenolpyruvate carboxykinase (PEPCK) is allosterically regulated by hormones.
There is no direct hormonal regulation of the enzyme’s activity. However there is a strong regulation of the expression of the gene. Look up which enzyme activates and which inhibits the enzyme.
18) Indicate how of the conditions effect gluconeogenesis.
19) Which of the following hormones bind to the alpha adrenergic receptor
20) All of the following are gluconeogenic enzymes except:
21) Why can’t gluconeogenesis just reverse the actions of pyruvate kinase by coupling the reaction with ATP?