Figure 4

Possible pathways for lipoic acid attachment to mitochondrial α-ketodehydrogenase apoenzymes. AMP-activated forms of free lipoic acid could be a source of direct lipoylation via LIPT1 (the “lipoic acid salvage pathway”). This mechanism is at odds with some data in mice and yeast, yet it may account for apparent compensatory effects observed in the human disorders (see text). Another mechanism proposed in yeasts [15] may involve the H protein of the glycine cleavage system as a donor of lipoyl redidues to the other complexes via LIPT1. In this case, the de novo pathway involving LIPT2 and LIAS would act only on the H protein. This partly accounts for the different amino acid profiles observed in patients. The action of LIPT1 on BCKDH may be more complex than for other dehydrogenases (see text).