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Alternative NADH dehydrogenases (NADH:ubiquinone oxidoreductases) are single subunit respiratory chain enzymes found in plant and fungal mitochondria and in many bacteria. It is unclear how these peripheral membrane proteins interact with their hydrophobic substrate ubiquinone. Known inhibitors of alternative NADH dehydrogenases bind with rather low affinities. We have identified 1-hydroxy-2-dodecyl-4(1H)quinolone as a high affinity inhibitor of alternative NADH dehydrogenase from Yarrowia lipolytica. Using this compound, we have analyzed the bisubstrate and inhibition kinetics for NADH and decylubiquinone. We found that the kinetics of alternative NADH dehydrogenase follow a ping-pong mechanism. This suggests that NADH and the ubiquinone headgroup interact with the same binding pocket in an alternating fashion.
Generation of reactive oxygen species (ROS) is increasingly recognized as an important cellular process involved in numerous physiological and pathophysiological processes. Complex I (NADH:ubiquinone oxidoreductase) is considered as one of the major sources of ROS within mitochondria. Yet, the exact site and mechanism of superoxide production by this large membrane-bound multiprotein complex has remained controversial. Here we show that isolated complex I from Yarrowia lipolytica forms superoxide at a rate of 0.15% of the rate measured for catalytic turnover. Superoxide production is not inhibited by ubiquinone analogous inhibitors. Because mutant complex I lacking a detectable iron-sulfur cluster N2 exhibited the same rate of ROS production, this terminal redox center could be excluded as a source of electrons. From the effect of different ubiquinone derivatives and pH on this side reaction of complex I we concluded that oxygen accepts electrons from FMNH or FMN semiquinone either directly or via more hydrophilic ubiquinone derivatives.
The transporter associated with antigen processing (TAP)-like (TAPL, ABCB9) belongs to the ATP-binding cassette transporter family, which translocates a vast variety of solutes across membranes. The function of this half-size transporter has not yet been determined. Here, we show that TAPL forms a homodimeric complex, which translocates peptides across the membrane. Peptide transport strictly requires ATP hydrolysis. The transport follows Michaelis-Menten kinetics with low affinity and high capacity. Different nucleotides bind and energize the transport with a slight predilection for purine bases. The peptide specificity is very broad, ranging from 6-mer up to at least 59-mer peptides with a preference for 23-mers. Peptides are recognized via their backbone, including the free N and C termini as well as side chain interactions. Although related to TAP, TAPL is unique as far as its interaction partners, transport properties, and substrate specificities are concerned, thus excluding that TAPL is part of the peptide-loading complex in the classic route of antigen processing via major histocompatibility complex class I molecules.
IAD annual report 2004/05
(2005)
What is the objective or purpose of business Management? According to the dominant theory of contemporary financial management scholarship, agency theory, business managers are obligated to maximise owner or shareholder value. According to most theories of business ethics, however, some owner-value-maximising actions should not be performed, because they would be unethical. Because business management scholars and business ethics scholars have not resolved this contradiction, students of commerce receive a contradictory education. The twenty-five essays in this interdisciplinary, international volume address the question of the objective or purpose of business management from a wide range of theoretical perspectives. Since some of the writers contradict one another, it is not possible that all of them are correct. Nevertheless, the fact that many of them argue persuasively that business managers should aspire to more than maximisation of a financial variable challenges everyone with a theoretical or practical interest in commerce to reconsider acceptance of the owner-value paradigm and to develop a richer conception of the profession of business management.
This book brings together multiple voices and positions from Africa. These voices, assembled during a 2003 Soap Summit held in Nairobi, are powerful and varied and suggest ways in which issues of health could be tackled in an entertaining manner. The summit organised by Population Communications International - Africa. highlighted the critical role that the arts can play in ensuring better health, especially among the youth. It resulted from the recognition that young people in Africa are faced with a myriad of problems and complications as they struggle to deal with growth and identity formation, within a globalising social and economic setup. They are in dire need of information on their own sexuality and how to deal with it and are getting conflicting signals from the mass media, as well as their immediate environment. The youth are under intense pressure from their peers to engage in premarital sex, which is in most cases unprotected. The HIV/AIDS epidemic presents frightening challenges and all health programs should look for ways of dealing with it. Of great to concern is the vulnerability of women and girls in Africa due to rising poverty, gender violence, lack of access to youth-friendly reproductive health facilities, and lack of a conducive infrastructure especially in informal settlements and in the rural areas. The myriad problems presented by the pandemic require a multi-sectoral approach. This book brings together a number of strategies being undertaken in Africa that combine entertainment and education in a positive way. The voices from the Soap Summit are interspersed with those of the Editor to create a dialogue on entertainment-education that contributes to the discussion on the way social change might be undertaken.
Chairman of Fools
(2005)
Chairman of Fools explores the plight of Farai Chari, a supposedly successful writer, professor and self-acclaimed artist, living in an African culture in which tradition weighs heavy and middle class aspirations are crude. Farai yearns for a world in which men and women can freely associate with one another and gratify their passions without moral chastisement.