TCA Cycle

Question 1

Where does the Tricarboxylic Acid (TCA) Cycle occur?

Answer 1

In the mitochondrial matrix

Question 2

The TCA cycle is a part of

Answer 2

Cellular respiration (aerobic process)

Question 3

The TCA consists of a series of ______ reactions that results in ________ to ___________

Answer 3

REDOX, oxidation of acetyl-CoA, 2 molecules of CO2

Question 4

4C (OA) + 2C (acetyl) –>

Answer 4

6C (citrate)

Question 5

Isomer of citrate is “oxidatively decarboxylated” to give

Answer 5

5C compound (alpha-Ketoglutarate)

Question 6

5C compound (alpha-Ketoglutarate) –>

Answer 6

4C (succinate) via oxidative decarboxylation

Question 7

OA is regenerated from

Answer 7

succinate (the cycle repeats)

Question 8

Label

Answer 8

Question 9

Properties of the TCA cycle:

Answer 9

• Aerobic
• Source of biosynthetic precursors
• Its activity depend of tissue type: Most active in brain, heart, kidney cortex, and liver
• Subcellular location: Enzymes within mitochondrial matrix except succinate dehydrogenase, which is located on the mitochondrial inner membrane.
• Compartmentalization - Inner mitochondrial membrane is impermeable to NADH, Acetyl CoA, Oxaloacetate; separate mitochondrial & cytosolic pools of each.

Question 10

Enzymes of the TCA Cycle

Answer 10

• Citrate synthase
• Aconitase
• Isocitrate dehydrogenase
• Alpha-ketoglutarate dehydrogenase complex
• Succinyl-CoA synthetase
• Succinate dehydrogenase
• Fumarase
• Malate dehydrogenase

Question 11

Pyruvate Dehydrogenase Complex (in mitochondrial matrix; not part of TCA cycle) consists of :

Answer 11

E1, pyruvate dehydrogenase (decarboxylation, TPP)

E2, dihydrolipoyl transacetylase (lipoamide, CoA)

E3, dihydrolipoyl dehydrogenase (FAD, NAD+)

Other components (regulatory): PDH kinase, protein phosphatase

Question 12

Last 3 steps that constitute a common “metabolic motif”

Answer 12

Oxidation→hydration→oxidation

Question 13

TCA Cycle is regulated:

Answer 13

• By energy charge: ATP, ADP
• By end product of the cycle: mitochondrial NADH
• At irreversible steps

Question 14

Irreversible steps cataylized by

Answer 14

–citrate synthase

–isocitrate dehydrogenase (major)

–alpha-ketoglutarate dehydrogenase

Question 15

Citrate synthase is allosterically regulated by

Answer 15

–NADH, succinyl-CoA, citrate, and ATP (inhibitors)

–ADP (activator)

Question 16

Isocitrate dehydrogenase is allosterically regulated by

Answer 16

–ATP (inhibitor); calcium and ADP (activators)

Question 17

Alpha-ketoglutarate dehydrogenase is regulated by

Answer 17

Succinyl-CoA and NADH (inhibitors) and calcium (activator)

Question 18

Pyruvate Dehydrogenase is allosterically inhibited by:

• _________
• _________
• _________

and allosterically activated by:

• _________
• _________
• _________

Answer 18

Allosterically inhibited by:

• ATP
• Acetyl CoA
• NADH

Allosterically activated by:

• AMP
• CoASH
• NAD+

Question 19

________ and ________stimulate PDH by promoting DEphosphorylation

Answer 19

Ca++, insulin

Question 20

Pyruvate dehydrogenase (PDH) inhibited by reversible phosphorylation of __________:

• PDH kinase: allosterically activated by ________
• ______________

Answer 20

• serine residue on E1
  
  • PHD kinases: allosterically activated by ATP
  • Protein phosphatase

Question 21

Intermediates are replenished through

Answer 21

anaplerosis

Question 23

Anaplerotic enzymes:

Answer 23

• pyruvate carboxlase (major)
• PEPCK
• Malic enzyme
• PEP carboxylase (plants, bacteria)

Question 24

A mutant form of IDH is present in ____________.

Answer 24

some cancers