Conformational basis of energy transduction in mitochondria
The conformational mechanism of energy transduction which we proposed in 1967 was based on an intuitive evaluation of the significance of large amplitude configurational changes which parallel energized processes in mitochondria [l-3] . By now a considerable body of information has been accumulated about the details of the configurational transitions in the mitochondrion [4-61. Moreover, the theory of structured systems with the capability for conservation of energy by a conformational mechanism is now being developed systematically [7]. This interplay of experiment and theory has made it possible to formulate the conformational hypothesis more explicitly and precisely. The tripartite repeating unit of the cristal membrane is the molecular unit of mitochondrial energy transduction. While in theory each repeating unit is a complete operational unit, in practice we are dealing with two dimensional arrays of repeating units within a membrane continuum and with the cooperative effects intrinsic to such arrays. Each repeating unit contains three basic systems which collectively effectuate the conformational transduction of energy. These systems are (a) the primary energizing system (one of the complexes of the electron transfer chain), (b) the conformational frame system, and (c) the discharge-directing system (the ATPase complex is one such system). The electron transfer process within each complex of the chain leads to a conformational transition [8-lo]. But since the electron transfer system is enclosed within a rigid frame (the conformational frame system [ 7]), the conformational expansion of
Swelling of mitochondria in crayfish gills
SummaryIn the gill processes ofAstacus leptodactylus Esch. fixed in the hypotonic glutaraldehyde fixative the mitochondria appear swollen to a different extent. The swelling occurs in a special way. Part of a single mitochondrion is swollen and the remaining part is frequently unchanged as in the control sections made of tissues fixed in the isotonic fixative. It is concluded that the mitochondrial matrix occurs in a semisolid state and osmotic swelling begins as a local liquefaction of the matrix which extends gradually over the total mitochondrion.
Stereoselective interaction between the R enantiomer of warfarin and cimetidine.
The stereoselectivity of the pharmacokinetic interaction between warfarin and cimetidine was investigated in eight healthy volunteers. The warfarin enantiomers were given separately as single doses (15 mg) alone and during chronic administration of cimetidine (1 g day-1). Cimetidine did not interact with S warfarin but there was an interaction with the R enantiomer of warfarin. Cimetidine caused a significant increase in the mean plasma half-life of R warfarin (from 47.8 h to 57.8 h) and a significant decrease in its mean plasma clearance (from 2.3 to 1.7 ml h-1 kg-1) (P less than 0.02). Administration of a pharmacological dose of vitamin K1 together with the enantiomers of warfarin was necessary clinically and resulted in elevation of vitamin K1 2,3-epoxide concentrations, which were similar in each case.