BIOLOGICAL TRANSPORT 



ATP from an action on the plasma membrane represents an over- 

 simplification. 



N-Ethylmaleimide has been shown to interfere with the action 

 of insulin on sugar transport and on the fixation of insulin by the 

 perfused heart (Candenas et al., 1961; cf. Pittman et al., 1961; 

 Fong et al., 1962). Attention has been called to the necessity of the 

 intact disulfide-bridged structure of insulin for its action on sugar 

 transport, and to the degree of similarity of its intrachain disulfide 

 bridge to that of vasopressin. Perhaps here also the hormone be- 

 comes fixed to the membrane by a disulfide exchange to modify its 

 behavior as proposed previously for vasopressin. 



Lehninger and Neubert (1961; Neubert and Lehninger, 1962) 

 find that the mitochondrion is stimulated to take up water in the 

 presence of vasopressin, oxytocin, or insulin, each at 10 ~ 4 to 10 ~ 5 

 M. This action resembles a much weaker one of oxidized glutathione. 

 Furthermore, the action in all these cases is potentiated by the 

 presence of reduced glutathione or certain other thiols. This water 

 uptake depends on simultaneous respiration, and the water is re- 

 extruded if ATP is added to the mitochondrial suspension. Melhuish 

 and Greenbaum (1961) have shown that zinc insulin and the pitui- 

 tary growth hormone (which contains four disulfide links) also 

 cause mitochondrial swelling. Although no formal demonstration 

 that these hormones bind by disulfide-sulfhydryl exchange is yet 

 available, the association of these effects, on the one hand, with the 

 action of simpler sulfur compounds and, on the other hand, with the 

 action of these hormones on other transport systems, establishes a 

 strong inference. 



The hormone levels required to provoke mitochondrial swelling 

 are high by biological standards. Lehninger and Neubert (1961) 

 do not suppose that all the hormones known to stimulate mito- 

 chondrial swelling act physiologically in this way. Instead, they em- 

 phasize that the same type of sandwiched, stratified lipid-protein 

 arrangement probably occurs in various cellular membranes, and 

 hence the action on the mitochondrion may serve as a model for 

 the action of the disulfide hormones on other membranes, including 

 the plasma membrane. These results further the concept that many 

 transports may find their common basis in the behavior of the pro- 

 tein structure of biological membranes, which is probably closely 

 associated with the transfer of energy involved in the formation 

 and breakdown of ATP (Christensen, 1960b; 1961; see closing para- 



102 



