Citric acid cycle location

In eukaryotes, electron transport and oxidative phosphorylation occur in the inner membrane of mitochondria. These processes re-oxidize the NADH and FADH2 that arise from the citric acid cycle (located in the mitochondrial matrix Topic L2), glycolysis (located in the cytoplasm Topic J3) and fatty acid oxidation (located in the mitochondrial matrix Topic K2) and trap the energy released as ATP. Oxidative phosphorylation is by far the major source of ATP in the cell. In prokaryotes, the components of electron transport and oxidative phosphorylation are located in the plasma membrane (see Topic Al). 

FADH is produced by succinate dehydrogenase in the citric acid cycle and by the a-glycerol phosphate shuttle. Both enzymes are located in the inner membrane and can reoxidize FADHj directly by transferring electrons into the ETC. Once FADH2 has been oxidized, the FAD can be made available once again for use by the enzyme. 

Acetyl-CoA is oxidized to C02 by the Krebs cycle, also called the tricarboxylic acid cycle or citric acid cycle. The origin of the acetyl-CoA may be pyruvate, fatty acids, amino acids, or the ketone bodies. The Krebs cycle may be considered the terminal oxidative pathway for all foodstuffs. It operates in the mitochondria, its enzymes being located in their matrices. Succinate dehydrogenase is located on the inner mitochondrial membrane and is part of the oxidative phosphorylation enzyme system as well (Chapter 17). The chemical reactions involved are summarized in Figure 18.7. The overall reaction from pyruvate can be represented by Equation (18.5) ... 

Pyruvate is converted into acetyl-CoA by a group of enzymes known as the pyruvate dehydrogenase complex (see Example 12.3 and Chap. 5). Acetyl-CoA and the enzymes that catalyze the steps of the citric acid cycle are situated within the matrix of the mitochondria, except for one enzyme that is located in the inner mitochondrial membrane. 

Inside the inner membrane of a mitochondrion is a viscous region known as the matrix (Fig. 1-9). Enzymes of the tricarboxylic acid (TCA) cycle (also known as the citric acid cycle and the Krebs cycle), as well as others, are located there. For substrates to be catabolized by the TCA cycle, they must cross two membranes to pass from the cytosol to the inside of a mitochondrion. Often the slowest or rate-limiting step in the oxidation of such substrates is their entry into the mitochondrial matrix. Because the inner mitochondrial membrane is highly impermeable to most molecules, transport across the membrane using a carrier or transporter (Chapter 3, Section 3.4A) is generally invoked to explain how various substances get into the matrix. These carriers, situated in the inner membrane, might shuttle important substrates from the lumen between the outer and the inner mitochondrial membranes to the matrix. Because of the inner membrane, important ions and substrates in the mitochondrial matrix do not leak out. Such permeability barriers between various subcellular compartments improve the overall efficiency of a cell. 

Oxidative phosphorylation is the process in which ATP molecules are formed as a result of the transfer of electrons from the reducing equivalents, NADH or FADH2 (produced by glycolysis, the citric acid cycle and fatty acid oxidation) to oxygen by a series of electron carriers in the form of a chain located in the inner membrane of mitochondria. This is the final reaction sequence of respiration. Since the electrons are transferred by a series of electron carriers in the form of a chain, it is known as electron transport system (ETS). 

In a eukaryotic cell, most of the enzymes of the citric acid cycle are located in the... 

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 enzymes that catalyze the p-oxidation of fatty acids are located in the matrix space of the mitochondria. Special transport mechanisms are required to bring fatty acid molecules into the mitochondrial matrix. Once inside, the fatty acids are degraded by the reactions of p-oxidation. As we will see, these reactions interact with oxidative phosphorylation and the citric acid cycle to produce ATP. 

A compound that is especially easy to observe is glutamate. This amino acid, most of which is found in the cytoplasm, is nevertheless in relatively rapid equilibrium with 2-oxoglutarate of the citric acid cycle in the mitochondria. The accompanying scheme shows where isotopic carbon from certain compounds will be located when it first enters the citric acid cycle and traces some of the labels into glutamate. For example, uniformly enriched fatty acids will introduce label into the two atoms of the pro-S arm of citrate and into 4- and 5-positions of glutamate whereas [2- C]acetate will introduce label only into the C4 position as marked by in the scheme. In the NMR spectrum a singlet resonance at 32.4 ppm will be observed. However, as successive turns of the citric acid cycle occur the isotope will appear in increasing amounts in the adjacent... 

A quick review of some aspects of mitochondrial structure is in order here because we shall want to describe the exact location of each of the components of the citric acid cycle and the electron transport chain. Recall from Chapter 1 that a mitochondrion has an inner and an outer membrane (Figure 19.2). The region enclosed by the inner membrane is called the mitochondrial matrix, and an intermembrane space exists between the inner and outer membranes. The inner membrane is a tight barrier between the matrix and the cytosol, and very few compounds can cross this barrier without a specific transport protein (Section 8.4). The reactions of the citric acid cycle take place in the matrix, except for the one in which the intermediate electron acceptor is FAD. The enzyme that catalyzes the FAD-linked reaction is an integral part of the inner mitochondrial membrane and is linked direcdy to the electron transport chain (Chapter 20). 

The citric acid cycle takes place in the mitochondrial matrix, with exception that one enzyme is located in the inner mitochondrial membrane. The closely related process of oxidative phosphorylation takes place in the inner mitochondrial membrane. 

Name the enzymes and the other components of the urea cycle, note their intracellular locations, and indicate the molecular connection between this cycle and the citric acid cycle. Account for the ATP requirement of the cycle. 

Fig. 4.22 The biochemical anatomy of mitochondria, showing the location enzymes of the citric acid cycle, the electron-transport chains, the en catalysing oxidative phosphorylation, and the internal pool of coenzymes. The muai membrane of a single liver mitochondrion may have over 10 000 sets of electron-transpKjrt chains and ATP synthetase molecules. The number of sets is proportional to the area of the inner membrane. Heart mitochondria, which have very profuse cristae and thus a much larger area of inner membrane, contain over three times as many sets of electron-transport systems as liver mitochondria. The internal pool of coenzymes and intermediates is functionally separate from the cytosolic pool.

PEPCK requires, in addition to oxaloacetate, its second substrate GTP or ITP. If the enzyme is located in the mitochondria, then GTP will also be necessary in the mitochondria. GTP is generated in substrate level phosphorylation by the citric acid cycle enzyme succinyl-CoA synthetase (reaction 3.9), which is present in the mitochondrial matrix. 

A mitochondrion contains both inner and outer membranes. As a result of extensive folding, the inner membrane has a surface area that is many times that of the outer membrane. The folds of the inner membrane are called cristae, and the gel-filled space that surrounds them is called the matrix. The enzymes for ATP synthesis (electron transport and oxidative phosphorylation) are located on the matrix side of the cristae. The enzymes for the citric acid cycle are found within the matrix, attached or near to the surface of the inner membrane. Thus, all the enzymes involved in the common catabolic pathway are in close proximity. 

The citric acid cycle is located in close cellular proximity to the electron transport chain. Why ... 

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