Alpha-ketoglutarate Dehydrogenase

• In the citric acid cycle:
• alpha-ketoglutarateàsuccinyl-CoA
• releases CO2, produces NAD
• α-ketoglutarate + CoA + NAD⁺ à succinyl CoA + NADH + CO₂
• Forms complex of 3 components (E1, E2, & E3)
• Coenzymes: thiamine pyrophosphate (E1), lipoic acid (E2), FAD (E3)
• Regulation:
• Increase ADP > ATP to stimulate
• Increase NAD > NADH to stimulate
• Increase CoA > succinyl-CoA to stimulate
• Increase [Ca2+] to stimulate
• Hormones:
• Stimulated by (Rashed, et al)
• Vasopressin
• Angiotensin II
• Phenylephrin
• High glucagon levels (lower levels require optimal Ca2+ levels)
• Structure
• 2-oxoglutarate dehydrogenase (OGDH) (Koike 1998)
• E1-component of the OGDH multi-enzyme complex
• Catalyzes both the ThDP-dependent decarboxylation of 2-oxoglutarate and the subsequent reductive succinylation of the lipoyl moiety which is covalently bound to the E2 component, dihydrolipoamide succinyltransferase.
• asdf
• Major metabolic role – TCA cycle
• Part of final common pathway of carbohydrate/protein/fat metabolism
• Source of carbon chain intermediates (i.e. oxaloglutarate à amino acids)
• Major energy source in aerobic respiration
• Etc