Oxidative phosphorylation efficiency

To gain further insight into the age-related adaptation of skeletal muscle to a more aerobic-oxidative metabolism, studying mitochondrial bioenergetic parameters and mitochondrial oxidative phosphorylation efficiency is of crucial importance. 

Two and twelve moles of ATP are produced, respectively, per mole of glucose consumed in the glycolytic pathway and each turn of the Krebs (citrate) cycle. In fat metaboHsm, many high energy bonds are produced per mole of fatty ester oxidized. Eor example, 129 high energy phosphate bonds are produced per mole of palmitate. Oxidative phosphorylation has a remarkable 75% efficiency. Three moles of ATP are utilized per transfer of two electrons, compared to the theoretical four. The process occurs via a series of reactions involving flavoproteins, quinones such as coenzyme Q, and cytochromes. 

Increase. Increased efficiency of oxidative phosphorylation increases the P/O quotient See E - 3.3. 

This is a very large negative AG° so the reaction is very strongly exergonic under standard conditions. Theoretically, enough free energy is liberated to phosphorylate seven molecules of ADP to ATP (AG for ADP phosphorylation + 30.5 kj/mol). In practice, oxidative phosphorylation is less than 50% efficient so only three ATP molecules are formed, the remainder of the energy is lost as heat. 

In contrast to substrate level phosphorylation in glycolysis, mitochondrial oxidative phosphorylation is an efficient process in that it generates in excess of 30 ATP per mole of glucose. In essence, the movement of electrons along the respiratory chain or electron transport chain is coupled with phosphorylation of ADP. 

However, the efficiency is clearly not a constant it depends on how the system is operated (i.e., on the ratio of the forces AjlJA). Thus when A/x+ is zero ( level flow ), the efficiency is zero. Similarly, when Ajxt assumes such a value that J is brought to a halt ( static head, also known as state 4 in oxidative phosphorylation), the efficiency is also zero. Between these two limiting states the efficiency passes through a maximum. The value of rjmax depends on a single parameter, the degree of coupling q [Kedem and Caplan, Trans. Faraday Soc., 61, 1897 (1965)] ... 

Depletion of ATP is caused by many toxic compounds, and this will result in a variety of biochemical changes. Although there are many ways for toxic compounds to cause a depletion of ATP in the cell, interference with mitochondrial oxidative phosphorylation is perhaps the most common. Thus, compounds, such as 2,4-dinitrophenol, which uncouple the production of ATP from the electron transport chain, will cause such an effect, but will also cause inhibition of electron transport or depletion of NADH. Excessive use of ATP or sequestration are other mechanisms, the latter being more fully described in relation to ethionine toxicity in chapter 7. Also, DNA damage, which causes the activation of poly(ADP-ribose) polymerase (PARP), may lead to ATP depletion (see below). A lack of ATP in the cell means that active transport into, out of, and within the cell is compromised or halted, with the result that the concentration of ions such as Na+, K+, and Ca2+ in particular compartments will change. Also, various synthetic biochemical processes such as protein synthesis, gluconeogenesis, and lipid synthesis will tend to be decreased. At the tissue level, this may mean that hepatocytes do not produce bile efficiently and proximal tubules do not actively reabsorb essential amino acids and glucose. 

In eukaryotes, oxidative phosphorylation occurs in mitochondria, photophosphorylation in chloroplasts. Oxidative phosphorylation involves the reduction of 02 to H20 with electrons donated by NADH and FADH2 it occurs equally well in light or darkness. Photophosphorylation involves the oxidation of H20 to 02, with NADP+ as ultimate electron acceptor it is absolutely dependent on the energy of light. Despite their differences, these two highly efficient energy-converting processes have fundamentally similar mechanisms. 

Oxidative phosphorylation produces most of the ATP made in aerobic cells. Complete oxidation of a molecule of glucose to C02 yields 30 or 32 ATP (Table 19-5). By comparison, glycolysis under anaerobic conditions (lactate fermentation) yields only 2 ATP per glucose. Clearly, the evolution of oxidative phosphorylation provided a tremendous increase in the energy efficiency of catabolism. Complete oxidation to C02 of the coenzyme A derivative of palmitate (16 0), which also occurs in the mitochondrial matrix, yields 108 ATP per palmitoyl-... 

Energy Efficiency of Aerobic Respiration (Oxidative Phosphorylation)... 

In order to extract the maximal energy out of the available foodstuff oxidative phosphorylation should operate at the state of optimal efficiency in vivo. Since a zero as well as an infinite load conductance both lead to a zero efficiency state, obviously there must be a finite value of the load conductance permitting the operation of the energy converter at optimal efficiency. For linear thermodynamic systems like the one given in equations (1) and (2) the theorem of minimal entropy production at steady state constitutes a general evolution criterion as well as a stability criterion.3 Therefore, the value of the load conductance permitting optimal efficiency of oxidative phosphorylation can be calculated by minimizing the entropy production of the system (oxidative phosphorylation with an attached load)... 

Let us first consider the problem of an appropriate degree of coupling of oxidative phosphorylation in the cell. The solution to this question depends entirely on what output function is to be optimized. We might for example require a maximal net flow of ATP at optimal efficiency (Jp) opt. As is evident from Fig. 4 there is a unique degree of coupling qf, which corresponds to the maximum of this output function (see also Table I). Such a low value of the degree of coupling has never been experi-... 

Fig. 9. Oxidative phosphorylation with a fluctuating load, (a) Plot of efficiency and force ratio versus time in the absence of adenylate kinase Z.AK = 0. The other parameters used for the simulation were as follows. Initial conditions ATP = 1.03, ADP = 0.234, AMP = 0.738. =11 N(0, ct2/2t). Constants Lp = 0.247, Lp = 0.0785, Lf = 0.0749, L = 0.0274, A(/ph s = 8.5 kcal/mole, P, = 0.008 M, AGak = 0.15 kcal, t = 20. ct = 0.1. time step of integration h = 0.01 time units. For further details see text and ref. 6.

Those who are familiar with, or have read the section on DNP are aware of the term "oxidative phosphorylation". This is a process by which cells/mitochondria convert ADP (Adenosine Diphosphate) into ATP (Adenosine Triphosphate). Basically this means adding another phosphate molecule to ADP so that it can be converted back into the body s energy /ATP. But the term keeps kids flunking biology anyway. DNP makes cells waste calories and burn fat by "uncoupling" the oxidative phosphorylation process and making it less efficient, even when at rest. 

DNP is an oxidative phosphorylation uncoupler. It makes the process only about 40% efficient by uncoupling a high energy phosphate molecule from ATP and therefore turning ATP into ADP. To maintain an adequate supply of ATP, the body must step-up production. For this reason metabolism is significantly increased and an incredible amount of calories are burned. During this accelerated metabolic state, and due to the need for ATP production, most of the calories come from fatty acids (adipose/fat tissue). So little or no muscle is lost (With adequate protein intake). 

Active fish have a better developed capillary system in the red muscle to supply oxygen to the mitochondria, and a higher haematocrit (Blaxter et al., 1971). The red muscle tissue also contains more cytochromes (respiratory proteins), and exhibits more cytochrome oxidase activity, which is responsible for transferring electrons in die respiratory chain, more efficient respiration control (oxidative phosphorylation and P/O coefficient) and a greater Atkinson charge, which characterizes energy reserve accumulated in adenyl nucleotides ... 

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