Lipoic Acid-dependent Complexes
2-OADH transfer reactions occur by a similar mechanism in the PDH complex, 2-oxoglutarate dehydrogenase (OGDH) complex, branched chain oxoacid dehydrogenase (BCDH) complex, and acetoin dehydrogenase (ADH) complex. The most studied of these is the PDH complex. These complexes have three central subunits: E1-3, which are the decarboxylase, lipoyl transferase, and dihydrolipoamide dehydrogenase respectively. These complexes have a central E2 core and the other subunits surround this core to form the complex. In the gap between these two subunits, the lipoyl domain ferries intermediates between the active sites. The geometry of the PDH E2 core is cubic in Gram-negative bacteria or dodecahedral in Eukaryotes and Gram-positive bacteria. Interestingly the 2-OGDH and BCDH geometry is always cubic. The lipoyl domain itself is attached by a flexible linker to the E2 core and the number of lipoyl domains varies from one to three for a given organism. The number of domains has been experimentally varied and seems to have little effect on growth until over nine are added, although more than three decreased activity of the complex. The lipoyl domains within a given complex are homogenous, while at least two major clusters of lipoyl domains exist in sequenced organisms.
Endogenous (enzyme-bound) (R)-lipoate also participates in transfer of acyl groups in the α-keto-glutarate dehydrogenase complex (KDHC or OGDC) and the branched-chain oxo acid dehydrogenase complex (BCOADC). RLA transfers a methylamine group in the glycine cleavage complex (GCV). RLA serves as co-factor to the acetoin dehydrogenase complex (ADC) catalyzing the conversion of acetoin (3-hydroxy-2-butanone) to acetaldehyde and acetyl coenzyme A, in some bacteria, allowing acetoin to be used as the sole carbon source.
The Glycine cleavage system differs from the other complexes, and has a different nomenclature. In this complex the H protein is a free lipoyl domain with additional helices, the L protein is a dihydrolipoamide dehydrogenase, the P protein is the decarboxylase, and the T protein transfers the methylamine from lipoate to tetrahydrofolate (THF) yielding methylene-THF and ammonia. Methylene-THF is then used by serine hydroxymethyltransferase (SHMT) to synthesize serine from glycine. This system is used by many organisms and plays a crucial role in the photosynthetic carbon cycle.
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