Mitochondria, concentration

In addition to these major processes, many other chemical events also occur. Mitochondria concentrate Ca2+ ions and control the entrance and exit of Na+, K+, dicarboxylates, amino acids, ADP, P and ATP, and many other substances.16 Thus, they exert regulatory functions both on catabolic and biosynthetic sequences. The glycine decarboxylase system (Fig. 15-20) is found in the mitochondrial matrix and is especially active in plant mitochondria (Fig. 23-37). Several cytochrome P450-dependent hydroxylation reactions, important to the biosynthesis and catabolism of steroid hormones and... 

Fig. 7.5. A schematic indication of some of the different membrane separated compartments in an advanced cell. PEROX is a peroxisome MITOCHLORO is either a mitochondrion or a chloroplast CHROMO is a vesicle of, say, the chromaffin granule ENDO is a reticulum, e.g. the endoplasmic reticulum. Other compartments are lysosomes, vacuoles, calcisomes and so on. Localised metal concentrations are shown. The figure is of a transverse section. To appreciate a cell fully it is necessary to have serial plane sections in parallel along the. "-direction.

The second phase of the process involves a massive increase in intracellular calcium concentrations. Interestingly, the calcium entry through NMDA receptors is particularly toxic, with one immediate pathogenic target of calcium entry being the mitochondrion [19]. 

A few patients have been described with a defect involving the carnitine-acylcarnitine translocase system, which facilitates the movement of long-chain acylcarnitine esters across the inner membrane of the mitochondrion (Fig. 42-2). These patients have extremely low carnitine concentrations and minimal dicarboxylic aciduria [4]. 

The control mechanisms operating on the TCA cycle are similar to those described for glycolysis above, that is allosteric and covalent. As might be predicted, it is the concentration of acetyl-CoA and the ATP-to-ADP and NADH-to-NAD+ ratios which are crucially important as these indicate energy status within each mitochondrion and implicitly therefore the energy status of the whole cell. High concentrations of ATP or NADH slow down the cycle, an effect which is partly mediated by covalent modification. 

As the power house of the cell, the mitochondrion is essential for energy metabolism. As the motor of cell death (1), this organelle is central to the initiation and regulation of apoptosis. In addition, mitochondria are critically involved in the modulation of intracellular calcium concentration and the mitochondrial respiratory chain is the major source of damaging reactive oxygen species. Mitochondria also play a crucial role in numerous catabolic and anabolic cellular pathways. 

What do I mean by a proton concentration gradient Simply, there is a higher concentration of protons in the space between the inner and outer membranes of the mitochondrion than in the mitochondrial interior. The gradient is formed from the energy released in the transfer of electrons down the electron transport chain. Put another way, the released energy is employed to pump protons across the inner mitochondrial membrane into the intermembrane space. 

In addition to the processes described above, there still remains one further process which, at least in some cells or tissues, is required prior to the utilisation of ATP in the cytosol that is, the transport of energy within the cytosol, via a shuttle. The transport of ATP out and ADP into the mitochondrion, via the translocase, results in a high ATP/ ADP concentration ratio in the cytosol. However, a high ratio means that the actual concentration of ADP in the cytosol is low, which could result in slow diffusion of ADP from a site of ATP utilisation back to the inner mitochondrial membrane. If sufficiently slow, it could limit the rate of ATP generation. To overcome this, a process exists that transports energy within the cytosol, not by diffusion of ATP and ADP, but by the diffusion of phosphocreatine and creatine, a process known as the phosphocreatine/creatine shuttle. The reactions involved in the shuttle in muscle help to explain the significance of the process. They are ... 

Oxidizible substrates from glycolysis, fatty acid or protein catabolism enter the mitochondrion in the form of acetyl-CoA, or as other intermediaries of the Krebs cycle, which resides within the mitochondrial matrix. Reducing equivalents in the form of NADH and FADH pass electrons to complex I (NADH-ubiquinone oxidore-ductase) or complex II (succinate dehydrogenase) of the electron transport chain, respectively. Electrons pass from complex I and II to complex III (ubiquinol-cyto-chrome c oxidoreductase) and then to complex IV (cytochrome c oxidase) which accumulates four electrons and then tetravalently reduces O2 to water. Protons are pumped into the inner membrane space at complexes I, II and IV and then diffuse down their concentration gradient through complex V (FoFi-ATPase), where their potential energy is captured in the form of ATP. In this way, ATP formation is coupled to electron transport and the formation of water, a process termed oxidative phosphorylation (OXPHOS). 

Opening of leads to a local increase in the cytosolic Ca concentration from 10 M to 10 M. In this concentration region, the Ca transport systems mentioned above work very efficiently. However, if an increase in Ca concentration over lO M takes place, e.g., due to cell damage, a level critical for the cell is reached. In this case, Ca is pumped into the mitochondria with the help of Ca transport systems localized in the iimer membrane of the mitochondrion. 

As salicylate is a weak acid and has sufficient lipid solubility, it is able to diffuse across membranes. Thus, it can cross the mitochondrial membranes in its protonated form, releasing the proton into the matrix of the mitochondrion. By increasing the proton concentration, this dissipates the proton gradient and thus halts ATP production (Fig. 7.60). 

The mechanism by which the mineral leaves the mitochondrion is only one of the problems of this theory. The mineral in the mitochondrion exists in association with the fluid contents. Thus, unless this water is in some structural form with abnormal solubilities, the mineral must be saturating the fluid, and solubility products apply. It follows that the mitochondrial calcium and phosphate concentrations must be similar to those of the extracellular fluids, i. e. calcium must be concentrated thousandfold to overcome the low intracellular values. 

In bacteria and green plants PEP carboxylase (Eq. 13-53), a highly regulated enzyme, is responsible for synthesizing oxaloacetate. In animal tissues pyruvate carboxylase (Eq. 14-3) plays the same role. The latter enzyme is almost inactive in the absence of the allosteric effector acetyl-CoA. For this reason, it went undetected for many years. In the presence of high concentrations of acetyl-CoA the enzyme is fully activated and provides for synthesis of a high enough concentration of oxaloacetate to permit the cycle to function. Even so, the oxaloacetate concentration in mitochondria is low, only 0.1 to 0.4 x 10-6 M (10-40 molecules per mitochondrion), and is relatively constant.65 79... 

What are the molar concentrations of the electron carriers in mitochondrial membranes In one experiment, cytochrome b was found in rat liver mitochondria to the extent of 0.28 pmol/g of protein. If we take a total mitochondrion as about 22% protein, the average concentration of the cytochrome would be 0.06 mM. Since all the cytochromes are concentrated in the inner membranes, which may account for 10% or less of the volume of the mitochondrion, the concentration of cytochromes may approach 1 mM in these membranes. This is sufficient to ensure rapid reactions with substrates. 

Let s now consider how much free energy is released by moving protons into the mitochondrion. Is it really enough to drive the synthesis of ATP The free energy change depends both on the ratio of the proton concentrations on the two sides of the membrane and on the difference between the electric potentials on the two sides. 

Mitchell based his concept on the suggestion that as electron is transported along the respiratory chain, H+ ions are ejected to cytoplasm (the mitochondrion environment). As a consequence, a gradient of H+ ion concentration occurs in external and internal mitochondrial spaces. Of course, this H+ ion concentration gradient is supported by electron transfer free energy decrease and in the case of membrane impermeability for H+ ions. 

Allen s theory of redox poise, and the evidence supporting it, are discussed in Chap. 3 of this volume. Here, I want to make a few general observations on necessity and workability. Each mitochondrion needs a genome because the speed of electron flow down the respiratory chains depends not just on supply and demand (concentration of NADH, 02, ADP and inorganic phosphate) but also on the number and redox state of respiratory complexes (Allen 1993,... 

Given the concentration of oxaloacetate and Avogadro s number, we can calculate the number of molecules in a mitochondrion ... 

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