Mitochondria citric acid cycle

The central role of the mitochondrion is immediately apparent, since it acts as the focus of carbohydrate, hpid, and amino acid metabohsm. It contains the enzymes of the citric acid cycle, P-oxidation of fatty acids, and ketogenesis, as well as the respiratory chain and ATP synthase. 

Rotte C, Stejskal F, Zhu G, Keithly JS, Martin W (2001) Pyruvate NADP+ oxidoreductase from the mitochondrion of Euglena gracilis and from the apicomplexan Cryptosporidium parvum a biochemical relic linking pyruvate metabolism in mitochondriate and amitochondriate protists. Mol Biol Evol 18 710-720 Schnarrenberger C, Martin W (2002) Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants. A case study of endosymbiotic gene transfer. Eur J Biochem 269 868-883... 

Eugene Kennedy and Albert Lehninger showed in 1948 that, in eulcaiyotes, the entire set of reactions of the citric acid cycle takes place in mitochondria. Isolated mitochondria were found to contain not only all the enzymes and coenzymes required for the citric acid cycle, but also all the enzymes and proteins necessaiy for the last stage of respiration—electron transfer and ATP synthesis by oxidative phosphoiylation. As we shall see in later chapters, mitochondria also contain the enzymes for the oxidation of fatty acids and some amino acids to acetyl-CoA, and the oxidative degradation of other amino acids to a-ketoglutarate, succinyl-CoA, or oxaloacetate. Thus, in nonphotosynthetic eulcaiyotes, the mitochondrion is the site of most energy-yielding... 

The carbon skeleton of oxaloacetate from the citric acid cycle (in the mitochondrion) is carried to the gly-oxysome in the form of aspartate. Aspartate is converted... 

T12. Fatty Acid Oxidation in Uncontrolled Diabetes When the acetyl-CoA produced during /3 oxidation in the liver exceeds the capacity of the citric acid cycle, the excess acetyl-CoA forms ketone bodies—acetone, acetoacetate, and D-/3-hydroxybutyrate. This occurs in severe, uncontrolled diabetes because the tissues cannot use glucose, they oxidize large amounts of fatty acids instead. Although acetyl-CoA is not toxic, the mitochondrion must divert the acetyl-CoA to ketone bodies. What problem would arise if acetyl-CoA were not converted to ketone bodies How does the diversion to ketone bodies solve the problem ... 

The carbamoyl phosphate, which functions as an activated carbamoyl group donor, now enters the urea cycle. The cycle has four enzymatic steps. First, carbamoyl phosphate donates its carbamoyl group to ornithine to form citrulline, with the release of Pj (Fig. 18-10, step ). Ornithine plays a role resembling that of oxaloacetate in the citric acid cycle, accepting material at each turn of the cycle. The reaction is catalyzed by ornithine transcarbamoylase, and the citrulline passes from the mitochondrion to the cytosol. 

Compartmentalization of Citric Acid Cycle Components Isocitrate dehydrogenase is found only in the mitochondrion, but malate dehydrogenase is found in both the cytosol and mitochondrion. What is the role of cytosolic malate dehydrogenase ... 

Formation of Oxaloacetate in a Mitochondrion In the last reaction of the citric acid cycle, malate is dehydrogenated to regenerate the oxaloacetate necessary for the entry of acetyl-CoA into the cycle ... 

Answer Malate dehydrogenase catalyzes the conversion of malate to oxaloacetate in the citric acid cycle, which takes place in the mitochondrion, and also plays a key role in the transport of reducing equivalents across the inner mitochondrial membrane via the malate-aspartate shuttle (Fig. 19-29). This shuttle requires the presence of malate dehydrogenase in the cytosol and the mitochondrial matrix. 

The main reason is probably that the system evolved to keep the fumarate concentration low, because fumarate (and arginine) readily inhibits argininosuccinate lyase. Thus, this enzyme is cytoplasmic it is not inhibited by the high concentration of fumarate from the citric acid cycle since this fumarate is in the mitochondrion. 

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. 

Figure 17.1. Mitochondrion. The double membrane of the mitochondrion is evident in this electron micrograph. The numerous invaginations of the inner mitochondrial membrane are called cristae. The oxidative decarboxylation of pyruvate and the sequence of reactions in the citric acid cycle take place within the matrix. [(Left) Omikron/Photo Researchers.]...

Recall that molecular oxygen does not participate directly in the citric acid cycle. However, the cycle operates only under aerobic conditions because NAD+ and FAD can be regenerated in the mitochondrion only by the transfer of electrons to molecular oxygen. Glycolysis has both an aerobic and an anaerobic mode, whereas the citric acid cycle is strictly aerobic. Glycolysis can proceed under anaerobic conditions because NAD+ is regenerated in the conversion of pyruvate into lactate. 

Krebs cycle A biochemical cycle in the second stage of cellular respiration involving eight steps that complete the metabolic breakdown of glucose molecules to carbon dioxide. Acetyl CoA is combined with oxaloac-etate to form citric acid. Citric acid is then converted into a number of other chemicals, and carbon dioxide is released. The process takes place within the mitochondrion. Also called citric acid cycle or tricarboxylic acid (TCA) cycle. Conceived and published by British scientist Sir Hans Adolf Krebs in 1957. 

Krebs cycle Citric acid cycle, TCA cycle, the mitochondrial process by which acetyl groups from acetyl-CoA are oxidized to CO. The reducing equivalents are captured as NADH and FADH, which feed into the electron transport system of the mitochondrion to produce ATP via oxidative phosphorylation. 

In eukaryotic cells aerobic metabolism occurs within the mitochondrion. Acetyl-CoA, the oxidation product of pyruvate, fatty acids, and certain amino acids (not shown), is oxidized by the reactions of the citric acid cycle within the mitochondrial matrix. The principal products of the cycle are the reduced coenzymes NADH and FADH, and C02. The high-energy electrons of NADH and FADH2 are subsequently donated to the electron transport chain (ETC), a series of electron carriers in the inner membrane. The terminal electron acceptor for the ETC is 02. The energy derived from the electron transport mechanism drives ATP synthesis by creating a proton gradient across the inner membrane. The large folded surface of the inner membrane is studded with ETC complexes, numerous types of transport proteins, and ATP synthase, the enzyme complex responsible for ATP synthesis. 

Although fatty acid synthesis occurs within the cytoplasm of most animal cells, liver is the major site for this process. (Recall, for example, that liver produces VLDL. See p. 349.) Fatty acids are synthesized when the diet is low in fat and/or high in carbohydrate or protein. Most fatty acids are synthesized from dietary glucose. As discussed, glucose is converted to pyruvate in the cytoplasm. After entering the mitochondrion, pyruvate is converted to acetyl-CoA, which condenses with oxaloacetate, a citric acid cycle intermediate, to form citrate. When mitochondrial citrate levels are sufficiently high (i.e., cellular energy requirements are low), citrate enters the cytoplasm, where it is cleaved to form acetyl-CoA and oxaloacetate. The net reaction for the synthesis of palmitic acid from acetyl-CoA is as follows ... 

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