Chapter 1   |   Metabolites go on journeys

Metabolism refers to a network of chemical reactions that occur within our cells and bodies to sustain life. Metabolic flux is a key concept while learning about homeostasis and regulation of these reaction pathways. The American Society for Biochemistry and Molecular Biology also considers Biochemical pathway dynamics and regulation to be a 'Threshold Concept' in Biochemistry i.e., an important concept that, when mastered, leads to a transformed understanding of the field. This concept describes reactions and interactions in biological systems to be dynamic and reversible. This chapter introduces the student to the very dynamic concept of metabolic flux and its significance.

 

1. This chapter can be viewed after students are introduced to biochemical pathways and homeostasis in Biochemistry and Metabolism

2. 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. This could be guided by the instructor.

3. The 'REFERENCES' section at the end contains additional learning resources.

INTRODUCTION

Metabolic flux is the passage of a metabolite through a given pathway over time. Examining the flow or flux of metabolites through pathways is a leading area of research in metabolism. Macro and microenvironments, hormonal signals and pharmacological perturbations draw unique metabolic flux responses in different cells leading to a diverse range of metabolic phenotypes. These fluxes help elucidate regulation at the level of transcription, translation, post-translation and protein-metabolite interaction. Fluxes are altered under disease conditions such as cardiovascular disease and cancer, so understanding them is of critical value to address treatment efforts. They also provide a look into how microbes are wired informing metabolic engineering as well.

flux and traffic similarities

This image from Christian Metallo and Matthew Vander Heiden (see reference 2 below) clearly depicts the similarities between metabolic flux and flow of traffic. The whole network of roads will determine how vehicles move along. If there is a roadblock along point 'A' in the Google Map on the left, then it will lead to slower movement of traffic (red lines) at a given time on certain roads leading to A, and other routes may be available nearby for faster movement of traffic (green lines). Similarly, if you consider the biochemical pathway on the right, decreased flux of AcCoA to citrate at point 'B' could lead to increased flux of aKG to citrate (green arrow). This illustrates how networks whether roads or metabolic pathways are interconnected and changes in flux in one part may be transmitted to other parts, resulting in a global response.

QUESTIONS

1. Can you explain metabolic flux in your own words in 2-3 lines to a friend or family member?

2. If a new roadblock appeared at the turn of Warburg St. in the Google Map image, which pathway(s) would be affected, and which metabolites would build up if you compare it to the biochemical pathway in the image to the right?