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Chemistry LibreTexts

MP1. Overview of Metabolic Pathways: Catabolism

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  • Brief Summary Glycolysis
    • Tricarboxylic Acid (Kreb's) Cycle: The TCA cycle is an aerobic pathway which takes place in an intracellular organelle called the mitochondria. It takes pyruvate, the incompletely oxidized product from glycolysis, and finishes the job of oxidizing the 3C atoms all the way to CO2. First the pyruvate moves into the mitochondria where is is oxidized to the 2C molecule acetylCoA with the release of one CO2 by the enzyme pyruvate dehydrogenase. The acetyl-CoA then enters the TCA cycle where two more CO2 are released. As in glycolysis, C-C bonds are cleaved and C is oxidized by NAD+ and another related oxidizing agent, FAD. What is very different about this pathway is that instead of being a series of linear, sequential reactions with one reactant (glucose) and one product (two pryuvates), it is a cyclic pathway. This has significant consequences since if any of the reactants within the pathways becomes depleted, the whole cyclic pathway can slow down and stop. To see how this happens consider the molecule oxaloacetate (OAA) which condenses with acetyl-CoA to form citrate (see diagram below). In this reaction, one OAA is consumed. However, when the cycle returns, one malate is converted to OAA so there is no net loss of OAA, unless OAA is pulled out of the TCA cycle for other reactions, which happens.

    Figure: Pyruvate Dehydrogenase (mitochondrial) and the TCA Cycle

    Figure: Mitochondrial Electron Transport/Oxidative Phosphorylation

    textinsert OxPhos Mito

    Feeder Pathways: Other catabolic pathways produce products that can enter glycolysis or the TCA cycle. Two examples are given below.

    • Complex carbohydrates: In mammals, the major carbohydrate storage molecule is glycogen, a polymer of glucose linked a1-4 with a1-6 branches. The terminal acetal linkages in this highly branched polymer is cleaved sequentially at the ends not through hydrolysis but through phosphorolysis to produce lots of glucose-1-phosphate which can enter glycolysis.

    textinsert glycogenolysis

    • Lipids: Lipids are stored mostly as triacylglycerides in fat cells (adipocytes). When needed for energy, fatty acids are hydrolyzed from the glycerol backbone of the triacylglyceride, and send into cells where they broken down in an oxidative process to form acetyl-CoA with the concomitant production of lots of NADH and FADH2. These can then enter the mitochondrial oxidative phosphorylation/electrons transport system, which produces, under aerobic conditions, lots of ATP.

    textinsert fa oxidation

    • Proteins: When intracellular proteins get degraded, they from individual amino acids. The amine N is lost as it enters the urea cycle. The rest of some amino acid structures can be ultimately converted to acetyl-CoA or keto acids (like alpha-ketoglutarate- a-KG) that are TCA intermediate. These amino acids are called ketogenic. Alternatively, some amino acids, after deamination, are coveted to pyruvate which can either enter the TCA cycle or in the liver be used to synthesize glucose in an anabolic process. These amino acids are called glucogenic. Chemical reactions such as these can be used to replenish intermediates in the TCA cycle which can become depleted as they are withdraw for other reactions.

    textinsert prot degrad

    Now on to anabolic reactions.