Cytochrome oxidase synthesis

Chloramphenicol inhibits synthesis of functional cytochromes a, a, b, and Ci in yeast mitochondria in vivo (Clark-Walker and Linnane, 1966, 1967) and in animal cells (Firkin and Linnane, 1969 Kroon and deVries, 1969). The effect of CAP on cytochrome oxidase synthesis is especially pronounced in rapidly growing tissues like regenerating rat liver, mammalian embryos (Oerter, 1970), HeLa cells in suspension culture (Storrie and Attardi, 1973), and Locusta migratoiia (Weiss et al., 1972). 

Partial inhibition of cytochrome oxidase synthesis, or a total block of mitochondrial protein synthesis which does not exceed a 24-hour period on day 13, is largely reversible. However, all embryos die after complete inhibition of mitochondrial protein synthesis for 2 days. 

Copper deficiency in humans and other mammals is characterized by slow growth, hair loss, anemia, weight loss, emaciation, edema, altered ratios of dietary copper to molybdenum and other metals, impaired immune response, decreased cytochrome oxidase activity, central nervous system histopathology, decreased phospholipid synthesis, fetal absorption, and eventually death (NAS 1977 Gallagher 1979 Kirchgessner et al. 1979 USEPA 1980 ATSDR 1990 Percival 1995). 

ATP is synthesized. Addition of cyanide (CN ), which blocks electron transfer between cytochrome oxidase and 02, inhibits both respiration and ATP synthesis, (b) Mitochondria provided with succinate respire and synthesize ATP only when ADP and P, are added. Subsequent addition of venturicidin or oligomycin, inhibitors of ATP synthase, blocks both ATP synthesis and respiration. Dinitrophenol (DNP) is an uncoupler, allowing respiration to continue without ATP synthesis. 

Correct answer = D. Thirteen of the approximately 100 polypeptides required for oxidative phosphorylation are coded for by mitochondrial DNA, including the electron transport components cytochrome c and coenzyme Q. Oxygen directly oxidizes cytochrome oxidase. Succinate dehydrogenase directly reduces FAD. Cyanide inhibits electron flow, proton pumping, and ATP synthesis. 

Copper was recognized as nutritionally essential by 1924 and has since been found to function in many cellular proteins.470-474 Copper is so broadly distributed in foods that a deficiency has only rarely been observed in humans.4743 However, animals may sometimes receive inadequate amounts because absorption of Cu2+ is antagonized by Zn2+ and because copper may be tied up by molybdate as an inert complex. There are copper-deficient desert areas of Australia where neither plants nor animals survive. Copper-deficient animals have bone defects, hair color is lacking, and hemoglobin synthesis is impaired. Cytochrome oxidase activity is low. The protein elastin of arterial walls is poorly crosslinked and the arteries are weak. Genetic defects in copper metabolism can have similar effects. 

Cytochrome oxidase also serves as a proton pump, so that the process of electron transfer is associated with the vectorial transfer of protons across the membrane, and thus contributes to the establishment of the proton gradient which is used to drive the synthesis of ATP. Cytochrome oxidase is located in the inner mitochondrial membrane of animal, plant and yeast cells (the eukaryotes) and in the cell membrane of prokaryotes. The arrangement is represented schematically in Figure 58. The complexity of cytochrome oxidase and the problems associated with its solubilization from the membrane have presented great obstacles to the elucidation of the structure and mechanism of the enzyme, but its importance has resulted in an enormous literature, which has been reviewed frequently.1296 1299... 

Poole1305 has reviewed the bacterial cytochrome oxidases, and has drawn attention to features which are not present in the mitochondrial enzyme, and which reflect the metabolic diversity and adaptability of bacteria. These are (1) the synthesis of the oxidases is controlled dramatically by the prevailing environmental conditions (2) some oxidases are multifunctional, and may use electron acceptors other than dioxygen (3) more than one type of oxidase may be present, each terminating a branched electron-transfer pathway. 

M. K. F. Wikstrom, K. Krab, and M. Saraste, Cytochrome Oxidase A Synthesis. Academic Press, New York, 1981. 

Hofmann, G.E. and S.C. Hand (1990). Arrest of cytochrome c oxidase synthesis coordinated with catabolic arrest in dormant Artemia embryos. Am. J. Physiol. (Integrative, Regulatory Comp. Physiol. 27) 258 R1184-1191. 

The control of the respiration process and ATP synthesis shifts as the metabolic state of the mitochondria changes. In an isolated mitochondrion, control over the respiration process in state 4 is mainly due to the proton leak through the mitochondrial inner membrane. This type of control decreases from state 4 to state 3, while the control by the adenine nucleotide and the dicarboxylate carriers, cytochrome oxidase, increases. ATP utilizing reactions and transport activities also increase. Therefore, in state 3, most of the control is due to respiratory chain and substrate transport. 

Copper and Zinc in Aerobic Metabolism. Cytochrome oxidase, the terminal oxidase in the electron transport chain contains an atom of copper. On this enzyme the protons and electrons generated during oxidative metabolism combine with elemental oxygen to form water. During copper deficiency the tissue concentration of cytochrome oxidase is reduced. While the effects of lower cytochrome oxidase activity on exercise has not been described, it is likely that aerobic energy metabolism will be diminished. This effect of copper deficiency was first described in animals with myelin aplasls — the degeneration myelin (86). The oxidative process of phospholipid synthesis, a primary component of myelin, was depressed. Liver mitochondria had impaired respiratory activity (87). Cytochrome oxidase activity was also depressed in brain, heart and liver. 

When purple non-sulfur bacteria switch from photosynthesis in the light to respiration in the dark, the content of BChl a or is diminished, and the synthesis of cytochrome oxidase is increased [101]. In some bacteria, such as Rb. sphae-roides, two oxidases are formed, Cyt aa [90] and Cyt o. In most others (e.g. R. rubrum) only Cyt o is formed [97]. Work during the past decade has revealed a strong similarity between the electron transfer pathways in purple non-sulfur bacteria and in the mitochondrial inner membrane [92]. 

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