60 METABOLISM 



These are not the only mechanisms affecting the transfer of hydrogen to 

 molecular oxygen. Many animal, yeast and bacterial cells, for example, contain 

 flavoprotein (Schiitz and Theorell 1938). Flavoprotein, the " yellow enzyme " 

 of Warburg and Christian (1933), is riboflavin phosphate combined with a protein 

 group ; it is spontaneously oxidizable by molecular oxygen, but acts also as a 

 hydrogen carrier between dehydrogenase systems and the cytochrome system 

 (Ogston and Green 1935), and anaerobically between two dehydrogenase systems 

 (Dewan and Green 1938). It is reduced by co-enzyme I and may be related to 

 the dehydrogenase of co-enzyme I mentioned above, which Straub, Corran and 

 Green (1939) have shown to be a flavoprotein. 



The dehydrogenase systems are reversible (Quastel and Whetham 1924, Green 

 and Stickland 1934). If the reaction of succinic acid and methylene blue is allowed 

 to proceed in the presence of Bad. coli dehydrogenase until the dye is reduced, 

 and an excess of fumaric acid added, the leuco-methylene blue gradually becomes 

 reoxidized. The reversal is due to the action of the enzyme, for the destruction 

 of the enzyme by heat or the addition of an antiseptic completely inhibits the 

 reoxidization of the methylene blue. Since these reactions are reversible, it is 

 obvious that they will not take place in a given direction unless the hydrogen 

 donators and acceptors are in a suitable physical state for the removal of electrons 

 from the substance to be oxidized. 



Biological Redox Systems. — In a given reversible oxidation-reduction system 

 the state of oxidation may be measured by the tendency of the system to give 

 up electrons, and the state of reduction by the tendency to take up electrons. 



If a platinum electrode is immersed in a fluid containing such a system, an electrical 

 " half-cell " is produced, and a potential difference, depending on the availability of 

 electrons in the system, is set up at the electrode. When the half- cell is put into a circuit 

 with the normal hydrogen electrode as a standard half-ceU, the electromotive force that 

 develops will be a measure of the electrode potential in the system compared with that 

 of the standard half-cell. This force, measured in volts, is designated the Eh of the 

 system. A marked tendency to reduction results in a flow of electrons from the standard 

 half-cell ; i.e. the current flows from the system to the half-cell and the Eh is positive. 

 A system with a marked tendency to oxidation, on the other hand, since electrons flow 

 to the standard cell half-cell, is indicated by a negative Eh. 



The conception of Eh, the oxidation-reduction (or redox) potential (see Clark et al. 

 1928, McLeod 1930, Hewitt 1936) as a measure of reducing intensity may be appUed to 

 the reversible enzyme systems of the dehydrogenase type. Oxidation, for example, will 

 not proceed in a given system except in the presence of a system with a higher Eh. Thus 

 it wiU be seen that the absolute Eh value is of less importance than its value compared 

 with other systems, for a system of a high reducing intensity, characterized by a low Eh, 

 will be further reduced by a system with an even lower Eh. For the general character- 

 ization of each system, the Eh is determined in standard conditions, namely when equiva- 

 lent amounts of the reduced and oxidized forms are present in equilibrium at pH 7-5 

 and a temperature of 30° C. This characteristic Eh is designated Eg', and in general 

 it may be said that, in the proper circumstances, a system of a given E^' will in the oxidized 

 state be reduced by a system of lower Eq' and in the reduced state will be oxidized by 

 a system of higher Eq'. For example, the Eg' of the succinic-dehj'drogenase system is 

 about 0-00 volt, and that of cytochrome-cytochrome oxidase about -^- 012 volt. On 

 electronic grounds it is to be expected that the oxidation of the succinic acid to fumaric 

 will occur in the presence of oxidized cytochrome. 



