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Renewable resource: sulfur is used, replenished to produce lipoic acid

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17 October 2018

Model of the crystal structure of the lipoyl synthase enzyme (LipA) from the bacteria Mycobacterium tuberculosis revealing the destruction of one of its iron-sulfur clusters (orange and yellow balls) to use as a sulfur source for the production of lipoic acid. New research demonstrates that the iron-sulfur cluster that is destroyed during the production of lipoic acid is replaced by an iron-sulfur carrier protein, NfuA, so that LipA can continue to produce lipoic acid. Credit: Booker laboratory, Penn State.
Model of the crystal structure of the lipoyl synthase enzyme (LipA) from the bacteria Mycobacterium tuberculosis revealing the destruction of one of its iron-sulfur clusters (orange and yellow balls) to use as a sulfur source for the production of lipoic acid. New research demonstrates that the iron-sulfur cluster that is destroyed during the production of lipoic acid is replaced by an iron-sulfur carrier protein, NfuA, so that LipA can continue to produce lipoic acid. Credit: Booker laboratory, Penn State.
New research shows how a protein is consumed and then reconstituted during the production of lipoic acid, a compound required by our bodies to convert energy from food into a form that can be used by our cells. The lipoyl synthase enzyme (LipA) removes two hydrogen atoms from an inert carbon chain and replaces them with sulfur atoms from one of its own iron-sulfur clusters to create lipoic acid, rendering itself inactive in the process.

“LipA cannibalizes itself to provide the sulfur atoms needed for the production of lipoic acid,” said Squire Booker, professor of chemistry and of biochemistry and molecular biology at Penn State and investigator of the Howard Hughes Medical Institute.

Another protein, an iron-sulfur cluster carrier called NfuA, replaces the destroyed iron-sulfur cluster in LipA, allowing it to continue producing lipoic acid. The results could help scientists to understand why humans with defects in the iron-sulfur carrier gene have deficiencies of lipoic acid.

“When we learned that humans with defective NFU1 genes—the human equivalent of the bacterial NfuA—had deficiencies in lipoic acid, we thought that this iron-sulfur carrier could be replacing the consumed iron-sulfur cluster in LipA, allowing it to continue making lipoic acid,” said Erin L. McCarthy, a graduate student in Booker’s laboratory.

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