Carbohydrate metabolism: TCA cycle

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Headshot of Ted Chauvin, PhD · Associate Professor
Ted Chauvin
PhD · Associate Professor
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If you read chapter 9, Tricarboxylic Acid Cycle and Pyruvate Dehydrogenase Complex, from Lippincott, you should have no issue with the objectives. The short descriptions listed below are some of the very big-picture, high-yield points. The reading and the class session will go into more depth and detail. The reading guide is also posted (you’ll see the pattern). As I said in other modules, this reading guide is for people who have a difficult time focusing on these types of chapters. Most students DO NOT need to use the guide.

Tricarboxylic Acid Cycle and Pyruvate Dehydrogenase Complex. Lippincott® Illustrated Reviews: Biochemistry, 8e. Medical Education: Health Library.pdf

TCA cycle

Describe the key steps and rate-limiting enzymes of the tricarboxylic acid (TCA) cycle and explain their role in cellular energy metabolism

  • Arsenic poisoning (TCA cycle and PDHC) 
  • TCA Cycle and what influences its up- or down-regulation 
  • Isocitrate dehydrogenase 
  • α-ketoglutarate dehydrogenase complex 
  • Succinate dehydrogenase 
  • Thiamine deficiency and why it affects the TCA cycle and the PDHC 

 

Explain how pyruvate is converted to acetyl-CoA and describe the regulation of pyruvate dehydrogenase in cellular metabolism

  • Thiamine deficiency and why it affects the TCA cycle and the PDHC 
  • Pyruvate Dehydrogenase Complex 
  • Pyruvate Dehydrogenase Complex (know the five important cofactors) 
  • PDH Kinase/phosphatase 
  • Arsenic poisoning (TCA cycle and PDHC)  

 

Describe the etiology, pathophysiology, clinical presentation, and management of pyruvate dehydrogenase complex deficiency

  • Pyruvate Dehydrogenase Complex 
  • Pyruvate Dehydrogenase Complex (know the five important cofactors) 
  • Pyruvate Dehydrogenase Complex Deficiency 

Describe the key steps and rate-limiting enzymes of the tricarboxylic acid (TCA) cycle and explain their role in cellular energy metabolism

A quick ten-minute video from Osmosis sums up the TCA cycle very well. The three high-yield enzymes you need to pay attention to are:

    • Isocitrate dehydrogenase
    • α-ketoglutarate dehydrogenase complex
    • Succinate dehydrogenase

Describe how pyruvate supplies acetyl-CoA to the tricarboxylic acid (TCA) cycle and explain the control of this enzymatic step Explain how pyruvate is converted to acetyl-CoA and describe the regulation of pyruvate dehydrogenase in cellular metabolism

A few high-yield key take-home points with this objective:

    • The cell uses the pyruvate dehydrogenase complex (PDHC) to take decarboxylate pyruvate and make acetyl CoA for use in the TCA cycle
    • There are three components to this complex (E1, E2, and E3)
    • There are five cofactors that are essential:
      • thiamine pyrophosphate (TPP)  (E1)
      • CoA (E2)
      • lipoic acid (E2)
      • FAD (E3)
      • NAD (E3)

Note

This is not part of the TCA cycle.

Describe the etiology, pathophysiology, clinical presentation, and management of pyruvate dehydrogenase complex deficiency

When cells lose the ability to convert pyruvate to Acetyl CoA, pyruvate then goes to lactate (uh-oh . . . lactic acidosis!).

Symptoms include neurodegeneration, muscle spasticity, elevated lactic acid, poor muscle tone, abnormal eye movements, and poor visual tracking.

This is X-linked, and usually, there is an issue with the E1 subunit of PDHC.

Management depends on the severity of the disease. A low-carbohydrate, high-fat (since fatty acids directly produce acetyl CoA and bypass pyruvate dehydrogenase—think ketogenic) diet, and supplement with thiamine and lipoic acid.