Mitochondria transport into

Pymvate dehydrogenase is a mitochondrial enzyme, and fatty acid synthesis is a cytosohc pathway, but the mitochondrial membrane is impermeable to acetyl-CoA. Acetyl-CoA is made available in the cytosol from citrate synthesized in the mitochondrion, transported into the cytosol and cleaved in a reaction catalyzed by ATP-citrate lyase. 

Not all the cellular DNA is in the nucleus some is found in the mitochondria. In addition, mitochondria contain RNA as well as several enzymes used for protein synthesis. Interestingly, mitochond-rial RNA and DNA bear a closer resemblance to the nucleic acid of bacterial cells than they do to animal cells. For example, the rather small DNA molecule of the mitochondrion is circular and does not form nucleosomes. Its information is contained in approximately 16,500 nucleotides that func-tion in the synthesis of two ribosomal and 22 transfer RNAs (tRNAs). In addition, mitochondrial DNA codes for the synthesis of 13 proteins, all components of the respiratory chain and the oxidative phosphorylation system. Still, mitochondrial DNA does not contain sufficient information for the synthesis of all mitochondrial proteins most are coded by nuclear genes. Most mitochondrial proteins are synthesized in the cytosol from nuclear-derived messenger RNAs (mRNAs) and then transported into the mito-chondria, where they contribute to both the structural and the functional elements of this organelle. Because mitochondria are inherited cytoplasmically, an individual does not necessarily receive mitochondrial nucleic acid equally from each parent. In fact, mito-chondria are inherited maternally. 

Figure 9.16 The principle of the transfer shuttle of hydrogen atoms into the mitochondrion. A dehydrogenase in the cytosol generates XH from NADH. XH is transported into the mitochondrion where a second dehydrogenase catalyses a reaction in which the XH reduces NAD to NADH. X then returns to the cytosol. The nature of XH is considered in Figures 9.17 and 9.18.

F. The electrons that are generated from the first step in ethanol metabolism (catalyzed by alcohol dehydrogenase) are transported into the mitochondrion by these two shuttles. 

Fig. 7.3.1 The heme synthesis pathway starts in the mitochondrion. The next four steps proceed in the cytosol. Coproporphyrinogen oxidase is in the intermembrane space of the mitochondrion, and the last two enzymes reside at the mitochondral matrix side of the inner membrane. The product heme represses the first and rate-limiting enzyme -aminolevulinic acid (5-ALA) synthase at transcription, during the translation step, and by its transport into the mitochondrion... 

Fatty acyl-CoA esters formed at the cytosolic side of the outer mitochondrial membrane can be transported into the mitochondrion and oxidized to produce ATP, or they can be used in the cytosol to synthesize... 

The combined effect of exchanging extramitochon-drial ADP-3 and H2P04 for mitochondrial ATP-4 and OH is to move one proton into the mitochondrial matrix for every molecule of ATP that the mitochondrion releases into the cytosol. This proton translocation must be considered, along with the movement of protons through the ATP synthase, to account for the P-to-O ratio of oxidative phosphorylation. If three protons pass through the ATP synthase, and the adenine nucleotide and Pj transport systems move one additional proton, then four protons in total move into the matrix for each ATP molecule provided to the cytosol. 

Some proteins, especially those destined for the eukaryotic mitochondria and chloroplasts, are transported after their synthesis on free polysomes is complete. Such transport is known as posttranslational transport. In the case of posttranslational transport it is believed that the polypeptide to be transported must be unfolded from its native folded configuration by a system of polypeptide-chain-binding proteins (PCBs) before it can pass through the membrane. Posttranslational transport into the mitochondrion requires both ATP and a proton gradient. Presumably the energy from one or both of these sources is used to unfold the protein or separate it from the PCB system so that it can pass through the membrane. 

Answer NADH produced in the cytosol cannot cross the inner mitochondrial membrane, but must be oxidized if glycolysis is to continue. Reducing equivalents from NADH enter the mitochondrion by way of the malate-aspartate shuttle. NADH reduces oxaloacetate to form malate and NAD+, and the malate is transported into the mitochondrion. Cytosolic oxidation of glucose can continue, and the malate is converted back to oxaloacetate and NADH in the mitochondrion (see Fig. 19-29). 

The answer is b. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) Aerobic glycolysis can be defined as the oxidative conversion of glucose to two molecules of pyruvate. In the process, two molecules of ATP and two molecules of NADH are produced. Since reducing equivalents from the two molecules of NADH produced in the cytoplasm must be transported into the mitochondrion for oxidation, it is not known how many ATP molecules are produced. On the assumption that two ATP molecules are formed per molecule of NADH oxidized via the glycerol phosphate shuttle, the ATP yield in aerobic glycolysis can be calculated as six ATP molecules per mole of glucose utilized. 

E. Gluconeogenesis requires ATP, which is in short supply, turning up the catabolism of glucose to lactate in the absence of an intact electron transport chain. ADP cannot be transported into the mitochondrion because ATP, its antiporter partner, isn t made by oxidative phosphorylation as a result of cyanide inhibition of cytochrome oxidase. Metabolism of fatty acids and ketone bodies requires a functional electron transport chain for their metabolism, and these possibilities are also ruled out. 

Figure 36-4. The activation of fatty acids and transport into the mitochondrion via the carnitine shuttle. (Reproduced, with permission, from D.B. Marks, et al, Basic Medical Biochemistry A Clinical Approach, Philadelphia Lippincott...

In anaerobic conditions, cells can metabolize pyruvate to lactate or to ethanol plus CO2 (in the case of yeast), with the reoxidation of NADH. In aerobic conditions, pyruvate is transported into the mitochondrion, where pyruvate dehydrogenase converts it into acetyl CoA and CO2 (see Figure 8-5). 

Figure 16-26 presents an overview of protein import from the cytosol into the mitochondrial matrix, the route into the mitochondrion followed by most imported proteins. We will discuss in detail each step in protein transport into the matrix... 

Reducing power (i.e., NADH) can be transported into the mitochondrion by the malate shuttle. Malate can transport reducing power out of the mi-... 

In muscle, most of the fatty acids undergoing beta oxidation are completely oxidized to C02 and water. In liver, however, there is another major fate for fatty acids this is the formation of ketone bodies, namely acetoacetate and b-hydroxybutyrate. The fatty acids must be transported into the mitochondrion for normal beta oxidation. This may be a limiting factor for beta oxidation in many tissues and ketone-body formation in the liver. The extramitochondrial fatty-acyl portion of fatty-acyl CoA can be transferred across the outer mitochondrial membrane to carnitine by carnitine palmitoyltransferase I (CPTI). This enzyme is located on the inner side of the outer mitochondrial membrane. The acylcarnitine is now located in mitochondrial intermembrane space. The fatty-acid portion of acylcarnitine is then transported across the inner mitochondrial membrane to coenzyme A to form fatty-acyl CoA in the mitochondrial matrix. This translocation is catalyzed by carnitine palmitoyltransferase II (CPTII Fig. 14.1), located on the inner side of the inner membrane. This later translocation is also facilitated by camitine-acylcamitine translocase, located in the inner mitochondrial membrane. The CPTI is inhibited by malonyl CoA, an intermediate of fatty-acid synthesis (see Chapter 15). This inhibition occurs in all tissues that oxidize fatty acids. The level of malonyl CoA varies among tissues and with various nutritional and hormonal conditions. The sensitivity of CPTI to malonyl CoA also varies among tissues and with nutritional and hormonal conditions, even within a given tissue. Thus, fatty-acid oxidation may be controlled by the activity and relative inhibition of CPTI. 

The urea cycle converts ammonium ions into urea, which is less toxic. The sources of the atoms are shown in color and the intracellular locations of the reactions are indicated. Citrulline, formed in the reaction between ornithine and carbamoyl phosphate, is transported out of the mitochondrion and into the cytoplasm. Ornithine, a substrate for the formation of citrulline, is transported from the cytoplasm into the mitochondrion. 

Malate is then transported into the mitochondrion where it is reoxidized to oxaloacetate. Mitochondrial NAD is reduced in the process. These electrons are then used in oxidative phosphorylation to produce three ATP per NADH. Thus the energy yield of glycolysis in heart and liver cells is two ATP, produced by substrate level phosphorylation, plus six ATP (three ATP per NADH), produced by oxidative phosphorylation. This gives an energy yield of eight ATP per glucose. 

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