Biological Oxidation and Electron Transport Chain

Oxidation is defined as the loss of electrons and reduction as the gain of electrons.

1. Biological Oxidation Mr. S Maheen Abdul Rahman, M. Pharm. Assistant Professor Department of Pharmaceutical Chemistry PA College of Pharmacy (PACP) Mangalore, Karnataka.

2. Oxidation is defined as the loss of electrons and reduction as the gain of electrons . This may be illustrated by the interconversion of ferrous ion (Fe 2+ ) to ferric ion (Fe 3+ ). Biological Oxidation

3. The electron lost in the oxidation is accepted by an acceptor which is said to be reduced. Thus oxidation-reduction is a tightly coupled process. The general principle of oxidation-reduction applies to biological systems also. The oxidation of NADH to NAD+ coupled with the reduction of FMN to FMNH 2 is illustrated

4. electron transport chain (ETC) The energy-rich carbohydrates (particularly glucose ), fatty acids, and amino acids undergo a series of metabolic reactions and finally, get oxidized to CO 2 and H 2 O. The reducing equivalents from various metabolic intermediates are transferred to coenzymes NAD+ and FAD to produce , respectively, NADH and FADH 2 .

5. The latter two reduced coenzymes pass through the electron transport chain (ETC) or respiratory chain and, finally, reduce oxygen to water . The passage of electrons through the ETC is associated with the loss of free energy. A part of this free energy is utilized to generate ATP from ADP and Pi.

6. Its primary function is to transfer electrons from electron donors like NADH and FADH 2 to electron acceptors such as oxygen . This process helps to create a proton gradient across the membrane , which drives the synthesis of adenosine triphosphate (ATP) through ATP synthase. Overall, the ETC is essential for efficient energy production in cells . Functions of ETC

7. oxidative phosphorylation The transport of electrons through the ETC is linked with the release of free energy . The process of synthesizing ATP from ADP and Pi coupled with the electron transport chain is known as oxidative phosphorylation . The complex V (See Fig) of the inner mitochondrial membrane is the site of oxidative phosphorylation .

8. P:O ratio The P:O ratio refers to the number of inorganic phosphate molecules utilized for ATP generation for every atom of oxygen consumed. More appropriately , the P:O ratio represents the number of molecules of ATP synthesized per pair of electrons carried through ETC. The mitochondrial oxidation of NADH with a P:O ratio of 3 can be represented by the following equation : 2 NADH--- ???

9. mechanism of oxidative phosphorylation The most important among them-namely, chemical coupling, and chemiosmotic- are discussed below Chemical coupling hypothesis This hypothesis was put forth by Edward Slater (1953). According to this hypothesis, during the course of electron transfer in the respiratory chain, a series of phosphorylated high-energy intermediates is first produced which are utilized for the synthesis of ATP. These reactions are believed to be analogous to the substrate-level phosphorylation that occurs in glycolysis or citric acid cycle. However, this hypothesis lacks experimental evidence, since all attempts, so far, to isolate any one of the high-energy intermediates have not been successful.

10. Chemiosmotic hypothesis This mechanism, was originally proposed by Peter Mitchell . (1961), is now widely accepted. It explains how the transport of electrons through the respiratory chain is effectively utilized to produce ATP from ADP + Pi. The concept of the chemiosmotic hypothesis is comparable with energy stored in a battery separated by positive and negative charges.

11. inhibitors of the electron transport chain The inhibitors bind to one of the components of ETC and block the transport of electrons. (No ATP) The synthesis of ATP (phosphorylation) is dependent on electron transport . Hence, all the site-specific inhibitors of ETC also inhibit ATP formation . Three possible sites of action for the inhibitors of ETC are identified.

12. NADH and coenzyme Q: Fish poison rotenone , barbiturate drug amytal, and antibiotic piercidin A inhibit this site. Between cytochrome b and c1: Antimycin A -an antibiotic, and British antilewisite ( BAL ) -an antidote used against war-gas-are the two important inhibitors of the site between cytochrome b and c1. Inhibitors of cytochrome oxidase: Carbon monoxide , cyanide , hydrogen sulfide , and azide effectively inhibit cytochrome oxidase. Carbon monoxide reacts with the reduced form of the cytochrome while cyanide and azide react with the oxidized form.

13. inhibitors of oxidative phosphorylation (1. Uncouplers - 2,4-dinitrophenol (DNP), dinitro cresol, pentachlorophenol, trifluoro carbonyl cyanide, and phenylhydrazone (FCCP) ) 2. Physiological uncouplers ( thermogenin , thyroxine, and long-chain free fatty acids ) Explanations-HOMEWORK

14. Important possible Questions 10 Marks Define Glycolysis. Elaborate the pathway with structures. Define the TCA cycle. Elaborate the pathway with structures. Define HMP shunt. Elaborate the pathway with structures. 10 Marks Write in detail about glycogen storage disease. Give the pathway of Glycogenesis Give the pathway of Glycogenolysis Gluconeogenesis Write in detail about ETC and its diagram. Define oxidative Phosphorylation and its mechanism. 2 Marks Give the total number of ATPs produced from both glycolysis and TCA cycle Inhibitors of ETC Inhibitors of Oxidative phosphorylation Pasteur effect Crabtree effect What is the uses of NADPH What is anaplerotic reactions with examples Write about i nhibitors of the TCA cycle von Gierek's disea se Wernicke-Korsakoff syndrome

15. REFERENCE BOOK Textbook of Biochemistry by Satyanarayana and chakrapani