MWM 2.8: 7 Unforgettable Things About α-Ketoglutarate Dehydrogenase

7 Unforgettable Things About α-Ketoglutarate DehydrogenaseThis complex is so rich in biochemical concepts and relevance to health and disease. Having done the dirty work of looking at its organic chemistry mechanisms in the last lesson, here we explore broadly applicable biochemistry principles like energetic coupling and substrate channeling. We look at how thiamin deficiency, oxidative stress, arsenic, and heavy metal poisoning can affect metabolism, and how to recognize markers of these processes in blood or urine. We make the subtle yet critical distinction between oxidative stress and oxidative damage. We look at the role of this complex in Alzheimer’s disease.

We then turn to the product of this complex, succinyl CoA, to examine how it provides an entry into the cycle for odd-chain fatty acids and certain amino acids and an exit out of the cycle for the synthesis of heme. In doing so, we look at the roles of vitamins B12 and B6 in these processes, the use of methylmalonic acid to diagnose B12 deficiency, and the ability of B6 deficiency to cause sideroblastic anemia.

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