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This Journal of Biological Chemistry (JBC) Classic is an instructive example of the early application of organic chemistry to questions of biochemical interest. The author, Henry Drysdale Dakin, was trained as an organic chemist in England. From 1905 to 1914, he worked in the private laboratory of Christian A. Herter in New York City. After Herter's untimely death in 1910 at the age of 45, Dakin continued directing Herter's laboratory at Mrs. Herter's request ... (There will be more about Herter's role as a scientist and founder of the JBC in a future installment of JBC Classics.)

In 1914, Dakin returned to Europe to help in the war effort. He worked in a French military hospital on the development of antiseptics. "Dakin's Solution," a buffered hypochlorite solution, was an important antiseptic for treating wounds. He was also responsible for the use of N-chloro-p-toluenesulfonamide sodium salt (chloramine-T) for the sterilization of drinking water (2).

In 1916, Dakin married Mrs. Susan Dows Herter, and they moved to a house overlooking the Hudson River at Scarborough. He constructed his own private laboratory in an annex and worked alone, except for the help of an "elderly technician," for the rest of his career (2). Dakin is best known for his studies on the oxidations and reductions that take place in the "animal organism." He discovered the enzymes arginase and glyoxidase. He synthesized the hormone adrenalin. Dakin also developed a method using "wet" butanol for extraction of amino acids from a neutralized protein hydrolysate. This method allowed a relatively complete amino acid analysis of two proteins zein and gelatin (1, 2).

Dakin was one of the first 81 members of the American Society of Biological Chemists (ASBC) and one of the early members of the JBC Editorial Board on which he served from 1911 to 1930. Among his many papers this one was selected for the JBC Classics series because it introduces a novel and very important approach to studying metabolism. In the introduction, Dakin pointed out that studying the metabolism of fatty acids in animals is difficult because the intermediate oxidation products are rapidly oxidized further making them difficult to isolate and to thereby define individual steps in the process. He decided to "tag" the fatty acids with a phenyl group as a "difficultyly (sic) oxidizable aromatic nucleus" so that the phenyl derivatives of fatty acid oxidation intermediates could be isolated and their structures determined. He argued that even though the phenyl derivatives were unnatural and metabolically inert, studying the metabolism of the fatty acid side chain would "undoubtedly throw light upon the mode of oxidation of the purely fatty acid of related structure."

The experiments were classic in design. Test compounds were synthesized. Dogs were injected subcutaneously with a dilute aqueous solution containing 4-8 g of a compound, and urine was collected for 3 days. (One might wonder what the total volume of the dilute aqueous solution containing 8 g of phenylpropionic acid might have been and whether such a protocol would be approved by the committees of today that review animal studies.) The urine was fractionated in several steps, and finally, individual compounds were crystallized, re-crystallized, and characterized by derivatization and comparison to reference compounds.

This work, introducing the application of phenyl-tagged molecules in metabolic studies, predates the use of stable isotopes by nearly 20 years and of radioactive isotopes by more than 30 years, yet uses, for the first time, the same logic to trace biologically active molecules through complex metabolic reactions.

Robert D. Simoni, Robert L. Hill, and Martha Vaughan

	REFERENCES

TOP ARTICLE REFERENCES

1.	Chittenden, R. H. (1945) The First Twenty-five Years of the American Society of Biological Chemistry , Williams & Wilkins, Baltimore, MD
2.	Clarke, H. T. (1952) J. Biol. Chem. 198, 491[Free Full Text]

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