Integration of MetabolismHandoutINTRODUCTIONThe catabolism of glucose, the preferred source of energy for several tissues, and evenother carbohydrates are already well understood and their catabolic products were seen tobe integrated with several pathways. Just like sugars, catabolic reactions of proteins andlipids eventually connect intoglycolysisand thecitric acid cyclepathways as illustrated inFigure 1.Central to the oxidation of nutrients is thecitric acid cycle. In this pathway, the acetylgroup ofacetyl-CoAresulting from the catabolism of sugar, fatty acids, and some aminoacids is completely oxidized to CO2with the production of electron transporting coenzymes(NADH and FADH2). These coenzymes transfer electrons to O2through theelectrontransfer system(ETS).As discussed in the previous lessons, this electron transfer isassociated with proton pumping. This generates a proton motive force as proposed by thechemiosmotic hypothesis which will drive the synthesis of ATP. This process, calledoxidative phosphorylation, is the main mechanism by which ATP is synthesized in mosthuman cells.Figure 1. An Overview of Catabolic Pathways for Carbohydrates, Amino acids and Lipids.In the regulation of metabolic pathways, controlling the activities of enzyme plays animportant role. In particular, the enzyme catalyzing the firstcommitted reactionof thepathway are controlled by attachment of a molecule to anallosteric (non-active) siteonthe protein. This site has an effect on the enzyme’s activity, often by changing theconformation of the protein. The molecules most commonly used in this capacity are thenucleotides ATP, ADP, AMP, NAD+, and NADH. These regulators, known asallostericeffectors, may increase (positive effector) or decrease (negative effector) enzyme activity,depending on the prevailing conditions, altering the steric structure of the enzyme, usuallyaffecting the configuration of the active site. This alteration of the protein’s (the enzyme’s)structure either increases or decreases its affinity for its substrate, with the effect ofincreasing or decreasing the rate of reaction. The attachment of a molecule to the allosteric
site serves to send a signal to the enzyme, providing feedback. This feedback type of controlis effective as long as the chemical affecting it is bound to the enzyme. Once the overallconcentration of the chemical decreases, it will diffuse away from the protein, and the controlis relaxed.CONTROL OF CATABOLIC PATHWAYSCatabolic pathways are controlled by enzymes, proteins, electron carriers, and pumpsthat ensure that the remaining reactions can proceed. This is an important part in theregulation of the different pathways as some enzymes might be slowed down if thatparticular pathway is not much needed by an organism or they might be activated if the needfor that pathway arises. Whether a particular enzyme activity is released depends upon theenergy needsof the cell (as reflected by the levels of ATP, ADP, and AMP).