Oxidative phosphorylation mitochondrial sites

Azido 4-nitrophenol Oxidative phosphorylation uncoupling site in mitochondria More effective uncoupler than dinitio-phenol, attachment sites on inner mitochondrial membrane subunit 1 of Fi-ATPase (MW 56,000) and a protein of MW 31,000 58-61... 

It has been known for many years that the mitochondrion shows a respiration-linked transport of a number of ions. Of these, calcium has attracted the most attention since it depends on a specific transport system with high-affinity binding sites. The uptake of calcium usually also involves a permeant anion, but in the absence of this, protons are ejected as the electron transfer system operates. The result is either the accumulation of calcium salts in the mitochondrial matrix or an alkalinization of the interior of the mitochondrion. The transfer of calcium inwards stimulates oxygen utilization but provides an alternative to the oxidative phosphorylation of ADP618 ... 

Let us start by detecting the principal difference between the two possible forms of the use of membrane catalyst closed and open. In the case of the closed surface, active sites (H+ ions) generated during cell nutrition oxidation are located on both sides of the membrane in almost equal amounts. This does not mean equality of their concentrations in cytoplasm and the matrix. Hence, the same pair of H+ ions is consumed in both ATP synthesis (oxidative phosphorylation) and H20 production (respiration). In the case in where the mitochondrial surface is open, H+ ions would also be consumed in both reactions, the only difference being that now they begin competing for H+ ions. In reality, oxidative phosphorylation is unable to compete for H+ ions with respiration. The so-called proton pump , which promotes... 

Uncouplers. Uncouplers dissociate electron transport from photophosphorylation. Both noncyclic and cyclic phosphorylation are inhibited, but electron transport reactions are either unaffected or stimulated. Because uncouplers relieve the inhibition of electron transport imposed by energy transfer inhibitors, they are considered to act at a site closer to the electron transport chain than the site of phosphate uptake. In Figure 2, they are shown (site 2) as dissipating some form of conserved energy represented as on the noncyclic and cyclic ATP-gener-ating pathways. Perfluidone is the only herbicide identified to date that functions as a pure uncoupler at pH 8.0 (2). Compounds that uncouple photophosphorylation also uncouple mitochondrial oxidative phosphorylation. 

In cyclic photophosphorylation, no chemical substrate is consumed and the formation of ATP depends only on absorbed photons. ATP formation by this mechanism is believed to depend on cytochromes, analogous to mitochondrial oxidative phosphorylation (Arnon, Tsujimoto, and McSwain (9)), but the mechanism is still uncertain. The number of phosphorylation sites on the cyclic phosphorylation pathway is not known, but in theory could be two or more. 

ATP-ADP translocase is specifically inhibited by very low concentrations of atractyloside (a plant glycoside) or bongkrekic acid (an antibiotic from a mold). Atractyloside binds to the translocase when its nucleotide site faces the cytosol, whereas bongkrekic acid binds when this site faces the mitochondrial matrix. Oxidative phosphorylation stops soon after either inhibitor is added, showing that ATP-ADP translocase is essential. 

At the present time, it is the opinion of the present reviewers that Wilson and collaborators have not provided sufficient evidence to conclude that the adenine nucleotide carrier is electroneutral and near equilibrium, nor have they conclusively shown that the first two sites of oxidative phosphorylation are in near equilibrium, especially in view of the likelihood that the P/O ratio of the first two sites is 1.5 rather than 2 [230,231]. Therefore, we conclude that their studies do not convincingly exclude a role for the adenine nucleotide translocator in the control of mitochondrial respiration. 

A slowly progressive congenital neuromuscular disorder was reported in which the respiratory chain-linked energy transfer at a level common to all three energy coupling sites of respiratory chain was defective.52 Uncouplers of mitochondrial oxidative phosphorylation (2,4-dinitrophenol and carbonylcyanide-m-chlorophenylhydrazone) (5) produced mitochondrial myopathy in rats.53... 

The answer is b. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-115. Wilson, pp 287-3111) The chemiosmotic hypothesis of Mitchell describes the coupling of oxidative phosphorylation and electron transport. The movement of electrons along the electron transport chain allows protons to be pumped from the matrix of the mitochondria to the cytoplasmic side. The protons are pumped at three sites in the electron transport chain to produce a proton gradient. When protons flow back through proton channels of the asymmetrically oriented ATPase of the inner mitochondrial membrane, ATP is synthesized. 

The mitochondria are aerobic cell organelles that are responsible for most of the ATP production in eukaryotic cells. They are enclosed by a double membrane. The outer membrane permits low-molecular-weight molecules to pass through. The inner mitochondrial membrane, by contrast, is almost completely impermeable to most molecules. The inner mitochondrial membrane is the site where oxidative phosphorylation occurs. The enzymes of the citric acid cycle, of amino acid catabolism, and of fatty acid oxidation are located in the matrix space of the mitochondrion. 

The discovery in 1948 by Eugene Kennedy and Albert Lehninger that mitochondria are the site of oxidative phosphorylation in eukaryotes marked the beginning of the modern phase of studies in biological energy transductions. Mitochondria, like gramnegative bacteria, have two membranes (Fig. 19-1). The outer mitochondrial membrane is readily permeable to small molecules <5,000) and... 

Mitochondria (singular = mitochondrion) are the so-called "power plants" of eukaryotic cells because they are the major source of energy for these cells under aerobic conditions (when oxygen is present). Mitochondria are the sites where complex processes involved in energy generation (such as electron transport and oxidative phosphorylation) are found. The product of mitochondrial action is chemical energy stored in the form of adenosine triphosphate, more commonly called ATP. 

Fig. 5. Putative consequences of ROS, of excess intracellular Ca and impairment of mitochondrial oxidative phosphorylation to membrane structure and function. The putative sites of therapeutic intervention are indicated by double lines crossing the arrows.

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