GLUTARIC ACID is found in the wash water from sheep's wool and in the unripe sap of sugar beet. It crystallizes in large monoclinic prisms which melt at 97.5° C, and distils between 302° and 304° C, practically without decomposition. It is soluble in water, alcohol and ether. Its chemical composition is and it is prepared synthetically by conversion of trimethylene bromide into cyanide and hydrolysis of the latter; or from acetoacetic ester (q.v.), which, in the form of its sodium derivative, condenses with (3-iodopropionic ester to form acetoglutaric ester, from which glutaric acid is obtained by hydrolysis. It is also ob tained when sebacic, stearic and oleic acids are oxidized with nitric acid. By long heating the acid is converted into its anhydride, and glutarimide is obtained by distillation of ammonium glutarate. GLUTATHIONE, in physiological chemistry, a compound of glutamic acid and cysteine, which, by its catalytic action, pro motes oxidation in living tissues. The energy required for the processes of life is mainly supplied by oxidations which occur in every living cell or tissue. The materials concerned in such oxida tions are not directly attacked by the molecular oxygen with which they are in contact. Living tissues contain however certain agents which "activate" the molecules either of the oxygen or of the materials to be burnt, and by so raising the chemical potential of the systems involved induce oxidations.
For the most part such results are brought about in the living cell by substances which partake of the nature of enzymes (q.v.), being easily destroyed by heat at relatively low critical tempera tures. Certain oxidations in the cell are however secured by a chemical mechanism which cannot in any accepted sense be classed as enzymic. It involves the properties of certain sulphur com pounds which contain the thiol, or –SH, group. The hydrogen of this structural group is susceptible of easy oxidation, and its oxi dative removal results in the formation of a disulphide group, –S–S–. Two molecules of the thiol compound are thus concerned in the change as shown in the following simplified scheme The disulphide form under suitable conditions may be again re duced to the thiol form, and the two ,f orms may co-exist in adjust able equilibrium with a variety of oxidizing and reducing sub stances.
Most living cells and tissues contain a substance displaying the properties thus described. Its molecule contains linked together two of the amino-acid groupings which are present in proteins. It is a dipeptide composed of glutamic acid and cysteine (see PROTEINS), and has received the name of glutathione. The cys teine moiety carries the thiol (-SH) group through which the biological influence of the substance is exerted (see CYSTINE). It is clear from what has been already said that such a substance may assume—when respectively reduced or oxidized—two related forms which, since in what follows we have only to think of the sulphur groupings, may for simplicity's sake be written as GSH and GSSG. In the living cell the substance (whether oxidized or reduced) is present in very low concentration, but it is not there as a source of energy. It is a permanent constituent of the cell promoting by its presence the oxidation of other substances.
The nature of the influence of glutathione in the cell is suffi ciently indicated by the following considerations. Its reduced form, GSH, is, in the presence of traces of iron (which are always available in the living cell), readily oxidized by molecular oxygen. The oxidized form, GSSG, which then results is itself however freely reduced by certain other constituents in the living cell capable of yielding the necessary hydrogen. If for convenience we denote such tissue constituents by the expression the process involved may be thus represented: The significance of the events thus symbolized resides in the circumstances that cell materials which are not oxidized directly by molecular oxygen (or oxidized with extreme slowness) are freely, though indirectly, oxidized through the progress of the above reactions. The glutathione acts, so to speak, as a carrier of hydrogen from tissue materials to oxygen. It will be clear that by acting in this way as an intermediary a very small amount of the substance may promote the oxidation of an unlimited amount of material. Incidentally it may be noted that the mobilization of hydrogen on such lines promotes other aspects of oxidation in the cell. Its removal may convert a saturated molecule into one less saturated, rendering it more prone to oxidation in general. More over, during the spontaneous oxidation of the SH group hydrogen peroxide may arise, and this, in the presence of cell agencies known as peroxidases, may bring about secondary oxidations.
Glutathione when separated from the tissues and purified is ob tained as a snow-white amorphous powder. Alike in its oxidized and reduced form it is exceedingly soluble in water. It resists the action of the hydrolytic enzymes of the tissues, but on boiling with mineral acids it is resolved into its constituent amino-acids.
(F. G. H.)