Medical Importance
In Homo sapiens the dihydrolipoyl dehydrogenase enzyme is a subunit of at least
three enzyme complexes related to metabolic pathways, pyruvate
dehydrogenase complex, alpha-ketoglutarate dehydrogenase, and
2-oxoglutarate dehydrogenase. Because the origin of this enzyme
in all the prementioned complexes is from the same gene, locus
7q31-32, any mutations in the gene can potentially result in an
apparent deficiency of one, if not all of the complexes.
Some of the symptoms that may be noticed in a patient with a DLDH
deficiency include:
1. labored respiration
2. elevations in blood pyruvate, alpha-ketoglutarate, lactic acid,
and branched-chain amino acids
3. periods of hypoglycemia
4. developmental delay
5. hypotonia (relaxed tension, vasodialation)
The outcome for patients suffering from forms of this deficiency ranges from a lifetime dealing with mild fatigue during exercise to an untimely death. Treatments are based on the individual's needs, due largely to the wide range of variations the deficiency can take, and are usually based on dietary changes and/or supplementary intake of metabolic intermediates that are lacking.
A few of the allelic variants of the deficiency have been reported. Some of these may give insight into the stabilizing, or active regions of the enzyme. These possibilities will be examined in the Structure and Active Site portion of this paper.