A biochemical sulfur delivery service

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Science  20 Oct 2017:
Vol. 358, Issue 6361, pp. 307-308
DOI: 10.1126/science.aap9299

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A number of metabolically important enzyme complexes depend on lipoic acid as an essential cofactor. Lipoic acid consists of a chain of eight carbon atoms, terminated at one end by a carboxylate group and at the other by two sulfur atoms appended to the carbons in the sixth and eighth positions. The sulfur atoms can exist as a disulfide-bonded ring or as free thiols. Once attached to a lipoyl carrier protein in an enzyme complex (see the figure), the lipoyl cofactor “arm” roves around, exploiting the redox activity of the sulfurs to facilitate decarboxylation reactions (1). Deficiencies in the two-step process by which cells make this lipoyl cofactor have been linked to severe and often fatal genetic diseases (2). On page 373 of this issue, McCarthy and Booker now report insights into lipoyl cofactor biosynthesis that resolve a major conundrum (3).