In the frst of four oxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group. The immediate product is unstable, losing CO2 while still bound to the enzyme. The ˜-ketoglutarate dehydrogenase complex closely resembles the large enzyme complex that converts pyruvate to acetyl CoA, the pyruvate dehydrogenase complex in Figure 13–10. It likewise catalyzes an oxidation that produces NADH, CO2, and a high-energy thioester bond to coenzyme A (CoA). A phosphate molecule from solution displaces the CoA, forming a high-energy phosphate linkage to succinate. This phosphate is then passed to GDP to form GTP. (In bacteria and plants, ATP is formed instead.) In the third oxidation step in the cycle, FAD accepts two hydrogen atoms from succinate. The addition of water to fumarate places a hydroxyl group next to a carbonyl carbon. COO–COO–HOHHHHCCCisocitrate isocitrate dehydrogenase CO2COO–COO–COO–HHHOCCCoxalosuccinate intermediate COO–+ H+ H+COO–COO–HHHHOCCC˜-ketoglutarate succinate dehydrogenase COO–COO–HHHHCCsuccinate COO–COO–HHCCfumarate fumarase COO–COO–HOHHHCCmalate COO–COO–HHCCfumarate H2O˜-ketoglutarate dehydrogenase complex CO2 + H+ COO–COO–HHHHOCCC˜-ketoglutarate COO–HHHHOCCCsuccinyl-CoA HSCoASCoA+ H2OCOO–HHHHOCCCsuccinyl-CoA SCoACOO–COO–HHHHCCsuccinate HSCoA+ succinyl-CoA synthetase GTPGDPFADNADHFADH2NAD+NADHNAD+Pi Step 3 Step 4 Step 5 Step 6 Step 7 107
Step 8 In the last of four malate dehydrogenaseoxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group, regenerating the oxaloacetate + H+ needed for step 1. COO–
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