Figure 2.

- Lipoic Acid Synthetase (LIAS) biosynthesis and function, LIAS is essential in the maturation of lipoic acid (LA) which acts as cofactor for many enzymes. lipoic acid is bound to E2 and E3 subunits of the mitochondrial a-ketoacid dehydrogenase complex family (Pyruvate dehydrogenase, oxoglutarate (a ketoglutarate) dehydrogenase and branched chain ketoacid dehydrogenase, 2-oxoadipate dehydrogenase). lipoic acid is also bound to protein H in the Glycine cleavage system (GCS). Diseases which cause inhibition of any of ISC assembly step 3 proteins (shown in red and underlined) will affect the synthesis of the target apoprotein LIAS and subsequently the end product LA. As a result, all the biological process which include lipoic acid will be affected; the activity of a-ketoacid dehydrogenase complex family will decrease and the GCS activity will decrease which result in hyperglycinemia. ISC - Iron–sulfur clusters, 5,10-MTHF - 5, 10 methylene tetrahydrofolate, GCS - Glycine Cleavage System, THF - tetrahydrofolate