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Mitochondria: An Overview
Mitochondria are organelles, found in the cytoplasm of all eukaryotic cells. Their function is to convert energy found in nutrient molecules and store it in the form of adenosine triphosphate (ATP). ATP is the universal energy-yielding commodity in cells, used by enzymes to perform a wide range of cellular functions.
In order to carry out energy conversion, mitochondria require oxygen, which they convert to water. The purpose of our respiratory and circulatory systems is to deliver oxygen to the tissues for use by mitochondria, and to eliminate carbon dioxide. The consumption of oxygen by mitochondria is called cellular respiration.
Respiratory Control
The limitation placed on electron transport by the chemisosmotic gradient is termed respiratory control. Mitochondria are said to exercise respiratory control as long as they can restrict electron transport by means of the gradient. If the gradient is destroyed by damaging the membranes, respiratory control is abolished and electron transport can run freely.
Important principle
Electron transport is driven by the free energy that is available from the energy carriers, in turn obtained from substrates such as glutamate or Krebs intermediates. It is restricted by the chemiosmotic gradient. The only way electron transport can proceed is to the extent that the energy in the gradient is dissipated. Please note, however, that in healthy mitochondria the gradient is maintained. That is, electron transport keeps up with the utilization of the energy stored in the gradient. Even in the presence of ADP, which allows ATP synthetase to exploit the gradient, the chemiosmotic gradient is maintained at a set energy level.
Electron Pathways and Inhibition
No matter what substrate is used to fuel electron transport, only two entry points into the electron transport system are known to be used by living cells. Reduced nicotinamide adenine dinucleotide (NADH) captures the energy from some of the reactions in glycolysis as well as from some of the Krebs reactions. Its entry point is complex I of the ETS. Reduced flavin adenine dinucleotide (FADH2), part of complex II, captures energy from the oxidation of succinate to fumarate, so that succinate donates electrons (and free energy) at complex II.
Electron transport inhibitors act by binding one or more electron carriers, preventing electron transport directly. Changes in the rate of dissipation of the chemiosmotic gradient have no effect on the rate of electron transport with such inhibition. In fact, if electron transport is blocked the chemiosmotic gradient usually cannot be maintained.
A consequence of the separate pathways for entry of electrons is that in the presence of some electron transport inhibitors respiration can still occur. The effect of inhibition on electron transport depends on the path used by the electrons donated by the selected substrate.
An inhibitor may completely block electron transport by irreversibly binding to a binding site. For example, cyanide binds cytochrome oxidase so as to prevent the binding of oxygen. Electron transport is reduced to zero. Breathe all you want - you can't use any of the oxygen you take in. Rotenone, on the other hand, binds competitively, so that a trickle of electron flow is permitted. However, if the chemiosmotic gradient is relieved by membrane damage or addition of ADP or an uncoupling agent, the ETS can't speed up.
The separate pathways for entry of electrons affects the rates of electron transport on different substrates.
Rates of State IV Respiration Depend on the Substrate
In order for isolated mitochondria to conduct electron transport at a reasonable rate, a substrate should be chosen such that the reaction that oxidizes the substrate is coupled with the reduction of NAD or FAD, the high energy intermediates that donate electrons to the ETS. The more steps that intervene between initial oxidation of the substrate (which is added in excess) and the donation of electrons to the ETS, the slower respiration will be. Respiration on glutamate, for example, is slower than on succinate, because glutamate, glutamate dehydrogenase, and NAD must all bind a matrix enzyme, glutamate dehydrogenase. Glutamate is oxidized to alpha-ketoglutarate and NAD is reduced to NADH in the process. NADH must then diffuse to complex I to donate its electron pair. The diffusion process and binding to complex I constitutes a second step which slows the process considerably.
Succinate binds the succinate dehydrogenase complex directly, which oxidizes succinate to fumarate and reduces FAD in the process. The succinate dehydrogenase complex is complex II in fact, and includes FAD. Therefore once succinate (which is added in considerable excess) binds to the complex its electrons are immediately donated to the ETS.
As slow as respiration is on glutamate, it is even slower on fatty acids or other substrates for which there are multiple steps leading to the ETS. Respiration on succinate is as fast as it gets, experimentally.
