Metabolic pathways are a multi-step series of biochemical reactions either breaking down a nutrient molecule or building up a biomolecule via metabolic intermediates. The pathways in mammalian cells atleast are quite complex with many intersections. They are essential for maintaining the homeostasis of an organism. In this chapter, we will visualize how carbon flows through a few of those key pathways.
This animation shows carbon flux from glucose (6-carbon (C) metabolite) through the catabolic pathway of glycolysis where glucose is broken down into pyruvate (3C metabolite) in the cytosol. Note the energy consumed and released during this process.Click here to download
This is a zoomed version of glycolysis with a metabolite represented in its carbon chain structure. The cyan flash represents occurence of a reaction or conversion of a metabolite.Click here to download
This video shows the process of Fermentation - an anaerobic biochemical process in the cytosol. Imagine this mammalian cell to be a muscle cell while vigorously exercising. In that case, oxygen availability runs a bit low. Most of the pyruvate (3C metabolite) formed from glycolysis is reduced to lactate (3C metabolite). NADH is used up releasing NAD+ which is re-utilized during glycolysis to quickly produce more ATP for energy. In this case, carbon flux from glucose (6C metabolite) ends up in lactate (3C metabolite) that is mostly excreted from the cell.Click here to download
This animation shows the Kreb's Cycle or Tricarboxylic Acid Cycle (TCA) or Citric Acid Cycle. In this catabolic pathway, acetyl CoA (2C metabolite) formed from pyruvate (3C metabolite) in the mitochondria, is oxidised releasing a lot of energy in the process. Here, the initial carbon flux from glucose (6C metabolite) eventually goes on to get oxidised into carbon dioxide (1C metabolite). The cofactors/coenzymes will proceed to the electron transport chain at the inner mitochondrial membrane, where oxygen is reduced to water and the protons pumped through the membrane power ATP synthase to make a lot of ATP. This process is called aerobic respiration or oxidative phosphorylation.Click here to download
This is a zoomed version of the TCA cycle with a metabolite represented in its carbon chain structure. The cyan flash represents occurence of a reaction or conversion of a metabolite.Click here to download
The Malate-Aspartate or M-A Shuttle provides an important way to regulate glycolysis and lactate metabolism by transferring reducing equivalents (NADH) generated during these processes from the cytosol into the mitochondria for ATP production and utilization. Cytosolic NAD+ must then be regenerated to maintain glycolytic flux and lactate (3C metabolite) conversion to pyruvate (3C metabolite).Click here to download
This animation shows carbon flux through the catabolic Pentose Phosphate Pathway or PPP in the cytosol. Glucose 6-phosphate (6C metabolite) is oxidised to ribose 5-phosphate (5C metabolite) and reduced coenzymes are produced. The products of PPP fuel anabolic pathways like nucleotide and fatty acid synthesis.Click here to download
In some cases, citrate (6C metabolite) produced during the TCA cycle can lead to the production of acetyl CoA (2C metabolite) in the cytosol, that goes into the synthesis of fatty acids (many carbon metabolite). Since this is an anabolic reaction it uses energy carriers like NADP+ and requires energy in the form of ATP. Here, carbon flux through citrate to fatty acids could be attributed to carbon from glucose (6C metabolite) or glutamine (5C metabolite) (See Chapter 3).Click here to download
1. In the TCA cycle animation if conversion of pyruvate to acetyl-CoA is blocked what would happen? Do you know which enzyme carries out this reaction? Do you also know how pyruvate enters the mitochondrial matrix?
2. When do you think you would see a reverse flux of production of pyruvate from lactate?