Radical SAMe enzyme LIAS and Lipoic acid

About Lipoic acid.

“Very little free lipoic acid exists in the cell in the absence of supplementation. In fact, the molecule is biosynthesized in its cofactor form rather than as the free acid.

This biosynthetic pathway involves a bacterial-type acyl carrier protein (ACP) upon which the C8 fatty acyl backbone is constructed. In humans, LIPT2, an octanoyltransferase, is believed to transfer the octanoyl chain from octanoyl–ACP to the target lysyl residue only of the H protein, the LCP of the GCS.

….

LS belongs to the radical S-adenosylmethionine (SAM) superfamily of enzymes, which use a [4Fe–4S] cluster cofactor to cleave SAM reductively to produce a 5′-deoxyadenosyl 5′-radical (5′-dA·).

In LS catalysis, the 5′-dA is used to abstract hydrogen atoms (H·) from C6, and then from C8, of the octanoyllysyl residue to allow for sulfur attachment.

Unlike most radical SAM (RS) enzymes, which contain only one [4Fe–4S] cluster, LS contains two [4Fe–4S] clusters.” (R1)

This is about Lypoyl Synthase.

Lipoic acid is a cofactor for several enzymes and one of its roles is recycling TPP (thiamine pyrophosphate) after it reacted with metabolite.

I suspect people who are thiamine-dependent and live on high doses of thiamine, might not have sufficient production/recycling of Lipoic acid attached to the enzymes.

Notice that Lypoyl Synthase uses two Iron-Sulfur clusters and two SAMe. So it’s essentially depends on iron and methylation potential.