The Conversion of Thiocyanate Sulfur to Sulfate in the White Rat*

l:lle or&n and fate of thiocyanate ion in the body have been of interest for more than a century. It has been generally accepted that the ion does not readily permeate normal cell membranes; t.hc distribution of thiocyanate ion in the body is the basis of a method for determination of extracellular fluid volume (1). Despite its assumed extracellular localization, thiocyanate ion is physiologically active. Thus, it may reduce the blood pressure of essential hypertension (2), it may exhibit8 goitrogenic effects (3)? and it may inhibit enzyme systems such as the carbonic anhydrasc system (4). Whether small amounts of thiocyanate ion of endogenous origin are present in the serum and urine of various species has been a matter of some conjecture because methods for its determination in biological fluids have been subject to serious error. It, has been demonst,rsted, however, that ingestion of cyanide ion leads to excretion of increased amounts of thiocyanate ion in the urine (5), and an enzyme system has been isolated which will convert free sulfur and thiosulfate t,o thiocyanate in vitro (6). Intravenous injection of thiosulfate ion as an antidote for cyanide poisoning is well known (7). In att.empting to interpret the physiological activity of thiocyanate ion in terms of its chemical reactivity, we have become interested in the origin and fate of the sulfur portion of the molecule. In this connection, it is of importance to know whether sulfur, once incorporated in the ion, can participate in metabolic interchange with other sulfur-containing compounds. Several mechanisms for sulfur interchange suggest themselves. In vitro, thiocyanate ion is readily oxidized to sulfate and cyanide, or is reduced to sulfide and cyanide. In the body such reactions might have little effect on the thiocyanate content if the newly formed cyanide were eventually reconverted to thiocyanate by detoxication. On the other hand, the original thiocyanate sulfur, if released from thiocyanate ion, could be transformed by known pathways of sulfur metabolism. If sulfide ion were formed, it