Updated: 3/27/2017

Citric Acid Cycle

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  • Overview
    • Other names
      • Krebs cycle, tricarboxylic acid (TCA) cycle
    • Function
      • generate high amounts of NADH/FADH2 that act as fuel for ATP synthesis in the electron transport chain
    • Pathway
      • occurs in the mitochondria
      • requires O2 to function
      • net equation
        • acetyl-CoA + 3 NAD+ + FAD + GDP + Pi → 2CO2 + 3 NADH + FADH2 + GTP + CoA
          • will theoretically yield 12 ATP (if ETC were 100% efficient)
          • both carbons of acetyl-CoA leave as CO2 in two of the reactions
            • conversion of isocitrate to alpha ketoglutarate
            • conversion of alpha ketoglutarate to succinyl-CoA
      • Important enzymes
        • isocitrate dehydrogenase
          • stimulated by ↓ energy
            • ↑ ADP
          • inhibited by ↑ energy
            • ↑ ATP, NADH
        • α-ketoglutarate dehydrogenase complex
          • requires the same cofactors as the pyruvate dehydrogenase complex
            • B1, B2, B3, B5, lipoic acid
            • in alcoholics, B1 deficiency leads to Wernicke's encephalopathy
              • triad of ataxia, confusion, ophthalmoplegia
            • inhibited by ↑ energy
              • ↑ ATP, NADH
            • inhibited by ↑ intermediates in the cycle
              • ↑ succinyl-CoA
        • succinyl-CoA synthetase
          • generates GTP
        • succinate dehydrogenase
          • a member of both the citric acid cycle and the electron transport chain
      • important intermediates
        • citrate
          • functions to shuttle acetyl-CoA out of mitochondria for fatty acid synthesis
            • citrate shuttle
        • succinyl-CoA
          • building block for heme synthesis
        • fumarate
          • enters from the urea cycle
        • malate
          • functions as a gluconeogenic substrate
    • Regulation
      • energy status control
        • NO hormonal control

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(M1.BC.12.1) A 54-year-old male with a history of alcoholism is admitted to your service with ataxia, ophthalmoplegia and altered mental status. Which reaction below is likely impaired in this man?

QID: 100066
FIGURES:

Conversion of a-ketoglutarate to succinyl-CoA

69%

(333/480)

Conversion of succinate to fumarate

3%

(14/480)

Condensation of acetyl-CoA with oxaloacetate to form citrate

10%

(47/480)

Conversion of fumarate to malate

3%

(16/480)

Formation of oxaloacetate from malate

13%

(61/480)

M 1 E

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