Chapter 3   |   Journeys are interconnected

You were introduced to a few pathways in the previous chapter. Most of these metabolic reactions do not occur in isolation but are linked to each other. In this chapter you will see how some of them are interconnected. You will be able to visualize dynamic carbon flux through these interlinked central carbon metabolism pathways. Here, you will see the link between the breakdown (catabolism) and the build up process (anabolism) and consider the term amphibolic pathway when both occurs.

 

1. This chapter can be viewed after students have completed chapters 1-2 and are familiar with catabolic and anabolic pathways and their regulation in Biochemistry and Metabolism. Students can view the animations in the 'PATHWAYS' section at their own pace. Alternatively, since the animations do not have audio the instructor can describe the pathway while the students watch the animations in class.

2. These animations focus only on metabolites and do not contain any enzyme or cofactor information. This chapter does not provide information on where high energy electrons are used or released so the viewers can focus on carbon flux. The instructor needs to provide these details if desired.

3. Some sample discussion questions have been provided in the 'QUESTIONS' section at the bottom of this page. Students are encouraged to engage with these questions either on their own or in a group after viewing the animations. This could be guided by the instructor.

4. The fluxes visualized in these animations are derived from data in research publications listed in the 'REFERENCES' section at the end. The depicted fluxes are net fluxes in mammalian cells, so it is key to remember that forward and reverse fluxes for reversible reactions are not shown. The instructor may need to indicate that.

5. HOW TO READ THE ANIMATIONS? Each blue spherical particle you see in the animation represents a metabolite. This simplified representation has been used to clearly visualize the amount of flux. The unit of flux is nmoles/(h*µl of cells). In the animation, what occurs in 1 µl of cells in one hour has been shown in 1 cell in one second. It has been shown in one cell to show compartmentalization within a cell.

PATHWAYS

  Carbon Flux from Glucose

This animation shows how much carbon from glucose (blue) flows through central carbon metabolism pathways. The flux visualized in this video is from a transformed mammalian cell line and could be different based on cell type. Biomass is the cellular DNA, RNA, protein and fatty acid content. The pink circle is to indicate biomass production via serine biosynthesis pathway and the yellow circle is to denote flux into fatty acid synthesis.Click here to download

 

 

  Carbon Flux from Glutamine

This animation shows that carbon flux into the TCA cycle is not just from glucose (grey) but a major portion of it is from glutamine (magenta). It shows that glutamine contributes in a large way to oxidative phosphorylation or ATP production. The flux visualized in this video is from a transformed mammalian cell line and could be different based on cell type. Biomass is the cellular DNA, RNA, protein and fatty acid content. The pink circle is to indicate biomass production via serine biosynthesis pathway and the yellow circle is to denote flux into fatty acid synthesis.Click here to download

 

 

  Carbon Flux from Fatty Acids

This animation shows that carbon flux into the TCA cycle can also occur through fatty acids (orange). The flux visualized in this video is from a transformed mammalian cell line and could be different based on cell type. Biomass is the cellular DNA, RNA, protein and fatty acid content. The pink circle is to indicate biomass production via serine biosynthesis pathway and the yellow circle is to denote flux into fatty acid synthesis.Click here to download

QUESTIONS

1. If the respiratory chain is pharmacologically inhibited or there is impairment in mitochondrial function what would happen to flux towards biomass production? What would happen to the reductive carboxylation reaction of alpha-ketoglutarate into citrate?

2. What differences would there be in flux between a brain cell and a skeletal muscle cell?

REFERENCES

1. Fan et al., Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in normoxia and hypoxia. Mol Sys Biol. 9:712. 2013.

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