6. How Isocitrate Dehydrogenase Makes Oxalosuccinate Decarboxylate Itself

This lesson looks at the third step of the citric acid cycle in much more detail, digging into the organic chemistry concepts involved in the conversion of isocitrate to α-ketoglutarate. We dive deep into this because it’s the only way to explain why this step parts ways with most other decarboxylation reactions in that it does not require thiamin (vitamin B1). This, in turn, provides a basis for understanding why burning carbohydrate for fuel requires twice as much thiamin than burning fat, and why high-fat, low-carbohydrate, ketogenic diets can be used to overcome problems with thiamin deficiency or defects in thiamin-dependent enzymes. We conclude by looking at how this step allows the interconversion of amino acids and citric acid cycle intermediates, the role of vitamin B6 in this process, and the use of enzymes known as transaminases to diagnose B6 deficiency and liver dysfunction.