ETC Oxidative Phosphorylation II Lecture 7 PDF

THE ELECTRON TRANSPORT CHAIN & OXIDATIVE PHOSPHORYLATION II Nikita Sahadeo, Ph.D. Biochemistry Unit Department Of Preclinical Sciences Faculty of Medical Sciences University of the West Indies January 2024 REGULATION OF ATP SYNTHESIS Regulation of aerobic respiration is by feedback inhibition Exampl...

THE ELECTRON TRANSPORT CHAIN & OXIDATIVE PHOSPHORYLATION II Nikita Sahadeo, Ph.D. Biochemistry Unit Department Of Preclinical Sciences Faculty of Medical Sciences University of the West Indies January 2024 REGULATION OF ATP SYNTHESIS Regulation of aerobic respiration is by feedback inhibition Examples: glycolysis inhibited by ATP and by citrate pyruvate dehydrogenase inhibited by NADH citrate synthase inhibited by ATP the availability of ADP REGULATION OF ATP SYNTHESIS THE REGULATION OF CELLULAR RESPIRATION IS GOVERNED PRIMARILY BY THE NEED FOR ATP [ADP] controls the rate of O2 consumption Electrons do not flow through the ETC towards O2 unless ADP is simultaneously phosphorylated to ATP Electrons do not flow from fuel molecules to O2 unless ATP needs to be synthesized High [ADP] or low [ATP]/[ADP] drives oxidative phosphorylation THE REGULATION OF CELLULAR RESPIRATION IS GOVERNED PRIMARILY BY THE NEED FOR ATP Conditions Limiting the Rate of Respiration State 1 Availability of ADP and substrate State 2 Availability of substrate only State 3 The capacity of the respiratory chain itself, when all substrates and components are present in saturating amounts State 4 Availability of ADP only State 5 Availability of oxygen only The rate of respiration of mitochondria can be controlled by the availability of ADP. This is because oxidation and phosphorylation are tightly coupled; that is, oxidation cannot proceed via the respiratory chain without concomitant phosphorylation of ADP. INHIBITORS OF OXIDATIVE PHOSPHORYLATION They may be classified as: inhibitors of respiratory chain components inhibitors of oxidative phosphorylation; uncouplers of oxidative phosphorylation. INHIBITORS OF THE RESPIRATORY CHAIN Bind to different components of the electron transport chain Does not allow to change in a reversible form from an oxidized state to a reduced state Results in the accumulation of reduced forms prior to the inhibitor point, and oxidized forms of the components of the ETC down the line of inhibition point. INHIBITORS OF THE ETC Rotenone Piericidin A Antimycins: Cyanide Carbon monoxide Azide INHIBITORS OF ATP SYNTHASE Oligomycin Dicyclo hexyl carbo diimide (DCCD) THE CHEMIOSMOTIC THEORY THE CHEMIOSMOTIC THEORY UNCOUPLING PROTEINS UNCOUPLERS In damaged mitochondria, respiration (i.e., electron transport) may occur unaccompanied by oxidative phosphorylation. When this happens the mitochondria are said to be uncoupled. In the presence of an uncoupling agent, respiration is increased, but ATP is not formed and the energy created is released as heat. Symptoms due to uncoupling in vivo include increased respiration and temperature, rapid onset of rigor mortis, and liver damage due to mitochondrial toxicity. DINITROPHENOL