Biological complexity: producing lipoic acid (Introduction)

by David Turell @, Thursday, October 19, 2017, 19:21 (2592 days ago) @ David Turell

Lipoic acid is necessary to produce energy for cells. How it is generated by enzymes is shown:

https://phys.org/news/2017-10-renewable-resource-vital-lipoic-acid.html

"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. The new research ... shows that another protein, an iron-sulfur cluster carrier called NfuA, replaces the destroyed iron-sulfur cluster in LipA, allowing it to continue producing lipoic acid.

***

"'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 University, an investigator of the Howard Hughes Medical Institute, and the corresponding author of the research paper. "When we demonstrated this in 2011, it was perplexing because if LipA is destroyed, how could the cell make enough lipoic acid?"

"LipA is a member of the radical SAM (S-adenosylmethionine) family of enzymes. Like most radical SAM enzymes, it contains a cluster of four iron and four sulfur atoms, which it uses to convert SAM into a high energy radical. In turn, that radical can remove hydrogen atoms from other molecules, a step required to activate many important cellular metabolic reactions. The hydrogen atoms are replaced with sulfur to complete the process.

"Where the sulfur atoms that LipA uses to produce lipoic acid come from and how they are attached have been major questions in the field. How other enzymes attach oxygen atoms to inert carbon centers is fairly well understood. In those instances, oxygen, which is ubiquitously available in the atmosphere, is used to create high-energy radicals and is also the source of the appended oxygen atom. Sulfur, on the other hand, is not similarly available, but unlike most other radical SAM enzymes, LipA has an additional iron-sulfur cluster.

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"In this second experiment, the researchers showed that after the 32S originally present in LipA was consumed in the chemical reaction to produce lipoic acid, lipoic acid was produced containing 34S, which could only have come from their engineered NfuA.

"'We've been interested for quite some time in both the process that adds sulfur to an inert carbon compound to make lipoic acid and the source of the added sulfur," said Booker. "Lipoic acid is a vital component of the basic metabolic processes that keep our cells alive."

Comment: This is a complex interaction within a giant enzyme molecule and a gene. For cells to use energy this reaction is necessary on a continuous basis, which implies it was present at the beginning of life as a totally intact process. It could not have developed bit by bit. Moe evidence for intelligent design.


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