Bioc 460 - Dr. Miesfeld Spring 2008 1 of 12 pages Redox Reactions in Metabolism Supplemental Reading Key Concepts - Reduction potentials are a measurement of electron affinity - Coenzymes provide reactive groups that function in enzyme catalysis - The pyruvate dehydrogenase complex is a metabolic machine KEY CONCEPT QUESTIONS IN METABOLIC REDOX REACTIONS: What does the ΔE value of a coupled redox reaction tell you about electron transfer potential? What are coenzymes and how do they function in the pyruvate dehydrogenase reaction? Biochemical Applications of Coenzyme Biochemistry: Thiamin, also called vitamin B1, is an important enzyme cofactor required for a variety of metabolic reactions. Beriberi is a disease caused by thiamin deficiency resulting in severe weight loss and neurological symptoms. People that eat polished white rice as a sole source of nourishment can develop beriberi because polished rice lacks thiamin. Foods rich in thiamin include watermelon, sunflower seeds, black beans and thiamin enriched grains and breads. Reduction potentials are a measurement of electron affinity Before we begin discussing the Citrate Cycle (lecture 28), we need to describe several biological redox reactions (oxidation-reduction) that represent a form of energy conversion involving the transfer of electron pairs from organic substrates to the carrier molecules NAD+ and FAD. The energy available from redox reactions is due to differences in the electron affinity of two compounds and is an inherent property of each molecule based on molecular structure. Since electrons do not exist free in solution, electrons must be passed from one compound to another in a coupled redox reaction. Coupled redox reactions consist of two half reactions, 1) an oxidation reaction (loss of electrons) and 2) a reduction reaction (gain of electrons). Compounds that accept electrons are called oxidants and are reduced in the reaction, whereas compounds that donate electrons are called reductants and are said to be oxidized by loss of electrons. Redox reactions in biochemistry rarely involve molecular oxygen (O2) directly, but rather are characterized by the loss and gain of electrons from carbon. The terminology of biochemical redox reactions is the same as that used in inorganic chemistry. Namely, each half reaction consists of a conjugate redox pair represented by a molecule with and without an electron (e-). For example, Fe2+/Fe3+ is a conjugate redox pair in which the ferrous ion (Fe2+) is the reductant that loses an e- during oxidation to become a ferric ion (Fe3+): Fe2+ <--> Fe3+ + e- reductant oxidant Similarly, the reductant cuprous ion (Cu+) can be oxidized to form the oxidant cupric ion (Cu2+) plus an e- in the reaction: Cu+ <--> Cu2+ + e- reductant oxidantBioc 460 - Dr. Miesfeld Spring 2008 2 of 12 pages Figure 1. The two conjugate redox pairs in these reactions are Fe2+/Fe3+ and Cu+/Cu2+. We can now combine these two half reactions into a coupled redox reaction by reversing the direction of the Cu2+ reduction reaction such that the e- functions as the "common intermediate" shared by the Fe2+ oxidation and Cu2+ reduction half-reactions: Fe2+ <--> Fe3+ + e- (oxidation of Fe2+) Cu2+ + e- <--> Cu+ (reduction of Cu2+) Fe2+ + Cu2+ <--> Fe3+ + Cu+ (coupled redox reaction) The oxidation of Fe2+ and reduction of Cu2+ is a coupled redox reaction we will see in lecture 29 when we examine the function of the cytochrome c oxidase complex in the electron transport system. The combination of glycolysis, the citrate cycle and the electron transport system result in the complete oxidation of glucose to form CO2 and H2O by a process called aerobic respiration. The e- donor is glucose which functions as the reductant, and O2 is the e- acceptor (oxidant) that is reduced in the last step of the electron transport system to form H2O. The two conjugate redox pairs NAD+/NADH and FAD/FADH2 serve as the e- carriers linking glycolysis to the citrate cycle and electron transport chain. It is useful to think of glucose as biochemical "battery" containing stored energy in the form of electrons that can be used to synthesize ATP in the mitochondria as a result of proton motive force and oxidative phosphorylation. Figure 1 illustrates the relationship between methane (CH4), the most highly reduced form of carbon which has 8 e- that can be donated, and carbon dioxide (CO2) in which all of the e- shared by the C and O are tightly associated with the more electronegative O. The more electrons a carbon atom has available to donate in a redox reaction, the more reduced (less oxidized) it is. Hydrogen is less electronegative than carbon, and therefore electrons in C-H bonds are considered "owned" by the carbon. Similarly, since oxygen is more electronegative than carbon, the electrons in C-O and C=O bonds are all "owned" by the oxygen atom. Note that in biological redox reactions, often (but not always), an increase in oxidation state of a carbon is associated with a decrease in the number of hydrogen atoms. Unlike the oxidation of Fe3+ which simply involves the transfer of one e- to Cu2+, redox reactions in the citrate cycle (and indeed most all enzyme-catalyzed redox reactions) involve the transfer of electron pairs (2 e-) to the electron carrier molecules NAD+ and FAD. The reduction of NAD+ to NADH involves the transfer of a hydride ion (:H-), which contains 2 e- and 1 H+, and the release of a proton (H+) into solution NAD+ + 2 e- + 2 H+ <--> NADH + H+Bioc 460 - Dr. Miesfeld Spring 2008 3 of 12 pages Figure 2. In contrast, FAD is reduced by sequential addition of one hydrogen (1 e- and 1 H+) at a time to give the fully reduced FADH2 product FAD + 1 e- + 1 H+ <--> FADH + 1 e- + H+ <--> FADH2 Oxidations can also involve a direct combination with oxygen which oxidizes the carbon by pulling e- toward the more electronegative O atom. Enzymes that catalyze biochemical redox reactions are strictly called oxidoreductases, however, since most oxidation reactions involve the loss of one or more hydrogen atoms, they are often called dehydrogenases. We will look at the reduction of the coenzymes NAD+ and FAD by dehydrogenases in more detail later. The two primary energy conversion reactions in metabolism are 1) phosphoryl transfers involving ATP, and 2) redox reactions that transfer pairs of electrons between organic
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