Loss Of Oxidative Phosphorylation Research Articles

Influence of oxygen on growth, cytochrome synthesis and fermentation pattern in propionic acid bacteria.

Summary: The influence of oxygen on growth and cytochrome synthesis was investigated in four species of Propionibacterium. After anaerobic growth all species contained cytochrome b, cytochrome a or a 1, cytochrome a 2 and a carbon monoxide-binding pigment. Cytochrome b functions in an electron transport system from lactate to fumarate since the lactate-fumarate dismutation reaction, unlike lactate oxidation via methylene blue, was strongly inhibited by 2-n-heptyl-4-hydroxyquinoline-N-oxide (HOQNO). No species grew on agar plates under aerobic conditions but all grew in aerated media, though at different rates and with diminished synthesis of all cytochromes. In Propionibacterium freudenreichii and P. shermanii, which grew slower under aerobic conditions than P. rubrum and P. pentosaceum, cytochrome synthesis was more repressed by oxygen. Large amounts of pyruvate accumulated under aerobic conditions whereas acetate, propionate and succinate were not formed. The bacteria are therefore dependent on oxidative phosphorylation for energy under aerobic conditions. For P. freudenreichii an Y 0 value (g dry wt bacteria/g-atom oxygen taken up) of 15 was measured, suggesting a P/O value of 1 to 2. Absence of cytochrome synthesis resulting in the loss of oxidative phosphorylation may explain the absence of aerobic growth on agar plates.

Validity of the lysosomal theory in oligemic shock.

Increasing attention has been given to the role of the lysosome in the pathogenesis of disease and tissue injury including shock. Lysosomes were described by de Duve¹in 1955 as biochemically inactive acid hydrolases, surrounded by an intact membrane. If the membrane becomes permeable or disrupted these enzymes are activated. Under certain conditions, concentrated lysosomal preparations can hydrolyse phosphate esters, ribonucleic acid (RNA), and microsomal and mitochondrial membrane components, causing loss of oxidative phosphorylation.²For these reasons it has been suggested that lysosomes may play a major role in tissue destruction and may be the cause of irreversibility in shock. Increase of lysosomal enzymes in the cytoplasm has been demonstrated biochemically in genetic muscular dystrophy,³and shortly after ligation of the blood supply of a liver lobe.⁴Slater and Greenbaum,⁵however, were unable to detect rapid release of lysosomal enzymes after induction of acute liver necrosis.

Properties of an Oligomycin-sensitive Adenosine Diphosphate-Adenosine Triphosphate Exchange Reaction in Intact Beef Heart Mitochondria

Abstract Intact beef heart mitochondria having high acceptor control ratios catalyze an oligomycin-sensitive adenosine diphosphate-ATP exchange reaction in the presence of 6.0 mm Mg++ at a rate of about 400 to 600 mµmoles per min per mg of mitochondrial protein, or somewhat higher than the rate of oxidative phosphorylation in beef heart mitochondria. The oligomycin-sensitive component of the total ADP-ATP exchange activity is saturated with Mg++ at much lower concentrations (∼1.0 mm) than the oligomycin-insensitive component (∼8.0 mm). Gramicidin, valinomycin, aurovertin, azide, arsenate, and atractyloside inhibit the ADP-ATP exchange, to an extent not exceeding the inhibition by oligomycin, whereas the adenylate kinase activity is insensitive to these agents. Beef heart mitochondria also catalyze uridine diphosphate-UTP, cytidine diphosphate-CTP, guanosine diphosphate-GTP, and ADP-dCTP exchanges, but these are insensitive to oligomycin and occur at less than 10% of the rate of the ADP-ATP exchange. Freezing and thawing of beef heart mitochondria, which has been reported not to cause loss of oxidative phosphorylation as measured by the P:O ratio, caused loss of the oligomycin-sensitive ADP-ATP exchange, loss of acceptor control of respiration, and gain of ATPase activity. It is suggested that the loss of oligomycin-sensitive ADP-ATP exchange activity during preparation of phosphorylating submitochondrial particles is caused by a molecular transformation of the ATP-synthesizing system so that the affinity for ADP is decreased, with a resulting gain of ATPase activity.

Rare-earth fatty liver I. Octanoate oxidation and energy production

The effects of cerium administration on octanoate oxidation, oxidative phosphorylation and mitochondrial ATPase in liver have been studied. Complete inhibition of the fatty acid oxidase system and marked uncoupling of phosphorylation are shown 48 h after the administration of this rare earth. These defects are not as pronounced at 24 h. The addition of known co-factors that function in fatty acid oxidation failed to restore octanoate oxidation. Extensive mitochondrial damage, evidenced by the loss of oxidative phosphorylation and marked ATPase activity, could explain the inability of these livers to oxidize octanoic acid.