Electron transport chain phosphorylation

The term vitamin K2 was applied to 2-methyl-3-difarnesyl-l,4-naphthoquinone, m.p. 54 C, isolated from putrefied fish meal. It now includes a group of related natural compounds ( menaquinones ), differing in the number of isoprene units in the side chain and in their degree of unsaturation. These quinones also appear to be involved in the electron transport chain and oxidative phosphorylation. 

Glycolysis and the citric acid cycle (to be discussed in Chapter 20) are coupled via phosphofructokinase, because citrate, an intermediate in the citric acid cycle, is an allosteric inhibitor of phosphofructokinase. When the citric acid cycle reaches saturation, glycolysis (which feeds the citric acid cycle under aerobic conditions) slows down. The citric acid cycle directs electrons into the electron transport chain (for the purpose of ATP synthesis in oxidative phosphorylation) and also provides precursor molecules for biosynthetic pathways. Inhibition of glycolysis by citrate ensures that glucose will not be committed to these activities if the citric acid cycle is already saturated. 

FIGURE 20.1 Pyruvate produced hi glycolysis is oxidized in the tricarboxylic acid (TCA) cycle. Electrons liberated in this oxidation flow through the electron transport chain and drive the synthesis of ATP in oxidative phosphorylation. In eukaryotic cells, this overall process occurs in mitochondria. 

The two processes are electron transport and oxidative phosphorylation. NADH is reoxidised by the process of electron transport using the electron transport chain and the energy released from this process is harnessed by oxidative phosphorylation to generate ATP. We noted earlier that the two processes are intimately linked or coupled. Normally one cannot proceed without the other. 

During dtric add production there is massive generation of NADH but little demand for ATP. Thus the situation could quickly arise where there is no further ADP available for oxidative phosphorylation within the cells. This means that the electron transport chain cannot operate and no further oxidation of NADH can occur. 

The reason for this is that reoxidation of NADH via the alternative electron transport chain (not coupled to oxidative phosphorylation) liberates heat. 

As fuel molecules are oxidized, the electrons they have lost are used to make NADH and FADH2. The function of the electron transport chain and oxidative phosphorylation is to take electrons from these molecules and transfer them to oxygen, making ATP in the process. 

The electron transport chain gets its substrates from the NADH and FADH2 supplied by the TCA cycle. Since the TCA cycle and electron transport are both mitochondrial, the NADH generated by the TCA cycle can feed directly into oxidative phosphorylation. NADH that is generated outside the mitochondria (for example, in aerobic glycolysis) is not transported directly into the mitochondria and oxidized—that would be too easy. 

By the mid-1950s, therefore, it had become clear that oxidation in the tricarboxylic acid cycle yielded ATP. The steps had also been identified in the electron transport chain where this apparently took place. Most biochemists expected oxidative phosphorylation would occur analogously to substrate level phosphorylation, a view that was tenaciously and acrimoniously defended. Most hypotheses entailed the formation of some high-energy intermediate X Y which, in the presence of ADP and P( would release X and Y and yield ATP. A formulation of the chemical coupling hypothesis was introduced by Slater in 1953,... 

The spatial separation between the components of the electron transport chain and the site of ATP synthesis was incompatible with simple interpretations of the chemical coupling hypothesis. In 1964, Paul Boyer suggested that conformational changes in components in the electron transport system consequent to electron transfer might be coupled to ATP formation, the conformational coupling hypothesis. No evidence for direct association has been forthcoming but conformational changes in the subunits of the FI particle are now included in the current mechanism for oxidative phosphorylation. 

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. 

Reaction 15.12 would be catalyzed by the electron-transport chain, with coupled phosphorylation, and all the oxygen in the sulfite product would be derived from water (in contrast to the oxygenase, in which two thirds of the oxygen atoms in sulfite come from dioxygen). Overall, Equations 15.11 and 15.12 produce the same result as Equation 15.10. 

Mitochondrial diseases are often expressed as neuropathies and myopathies because brain and muscle are highly dependent on oxidative phosphorylation. Mitochondrial genes code for some of the components of the electron transport chain and oxidative phosphorylation, as well as some mitochondrial tRNA molecules. 

The final stage in the extraction of energy from food is oxidative phosphorylation, in which the energy of NADH and FADHj is released via the electron transport chain (ETC) and used by an ATP synthase to produce ATP. This process requires O. ... 

Many enzymes in the mitochondria, including those of the citric acid cycle and pyruvate dehydrogenase, produce NADH, aU of which can be oxidized in the electron transport chain and in the process, capture energy for ATP synthesis by oxidative phosphorylation. If NADH is produced in the cytoplasm, either the malate shuttle or the a-glycerol phosphate shuttle can transfer the electrons into the mitochondria for delivery to the ETC. Once NADH has been oxidized, the NAD can again be used by enzymes that require it. 

The metabolic machinery responsible for the heterotrophic respiration reactions is contained in specialized organelles called mitochondria. These reactions occur in three stages (1) glycolysis, (2) the Krebs or tricarboxylic acid cycle, and (3) the process of oxidative phosphorylation also known as the electron transport chain. As illustrated in... 

Porphyrin rings containing iron are also a feature of the cytochromes. Several cytochromes are responsible for the latter part of the electron transport chain of oxidative phosphorylation that provides the principal source of ATP for an aerobic cell (see Section 15.1.2). Their function involves alternate oxidation-reduction of the iron between Fe + (reduced form) and Fe + (oxidized form). The individual cytochromes vary structurally, and their classification (a, b, c, etc.) is related to their absorption maxima in the visible spectrum. They contain a haem system that is covalently bound to protein through thiol groups. 

This will be one of the processes shown, all of which have a large negative AG and are capable of harnessing this energy via synthesis of ATP molecules. However, even these are not achievable directly, and the electron transport chain of oxidative phosphorylation is utilized. 

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