PPP, PDH, & TCA Cycle

Question 1

What is the effect of a buildup of high energy molecules on TCA?

Answer 1

A buildup or NADH and ATP indicate the cell has adequate energy. TCA will be inhibited.

Question 2

G6PDH deficiency is the most common enzyme defect. How else may G6PDH deficiency be caused?

Answer 2

Consumption of uncooked fava beans

Question 3

What energy molecules are generated through TCA? How?

Answer 3

Oxidative Phosphorylation - 3 NADH, 1 FAHD2

Substrate-level phosphorylation - 1 GTP

Question 4

What molecules directly inhibit PDH?

Answer 4

Acetyl CoA & NADH (products of the complex)

Question 5

Where does the PPP take place?

Answer 5

Cytoplasm

Question 6

What are the two phases of the PPP? Are they reversible or irreversible?

Answer 6

Oxidative - Irreversible
Non-oxidative - Reversible

Question 7

What is the main enzyme involved in the oxidative phase of the PPP?

Answer 7

Glucose-6-Phosphate Dehydrogenase (G6PDH)

Question 8

PDH activity can be regulated directly by its substrates and products. How else can PDH activity be regulated?

Answer 8

Phosphorylation by the PDH kinase inhibits the complex. Dephosphorylation by the PDH phosphatase activates the complex.

Question 9

What is the rate-limiting step of TCA?

Answer 9

Isocitrate –> alpha-ketoglutarate via isocitrate dehydrogenase

Question 10

What enzymes regulate TCA?

Answer 10

Citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase

Question 11

What cofactors are necessary for PDH?

Answer 11

Thiamine/TPP (B1), Lipoic Acid, CoA (B5), FAD (B2), NAD+(B3),

Question 12

What is the effect of AMP and Ca2+ on TCA?

Answer 12

AMP and CA2+ indicate the cell is in need of energy. These molecules will stimulate TCA by activating the alpha-ketoglutarate dehydrogenase.

Question 13

What is the composition of the PDH complex?

Answer 13

A complex of 5 enzymes in the mitochondrial matrix that forms acetyl Co-A from pyruvate

Question 14

What is the effect of PDH deficiency?

Answer 14

PDH deficiency results in a buildup of pyruvate, which drives alanine and lactate production from pyruvate. This results in chronic lactic acidosis and possible neurological defects.

Question 15

What is the commitment step of TCA?

Answer 15

Acetyl-CoA –> Citrate via the citrate synthetase

Question 16

This type of reaction synthesizes and replenishes intermediates of TCA.

Answer 16

Anaplerotic reaction

Question 17

What is the significance of G6PDH deficiency?

Answer 17

G6PDH deficiency is an x-linked recessive disease and most common human enzyme defect in the world. Deficiency leads to hemolysis from oxidative stress due to a reduced ability to neutralize ROS.

Question 18

What treatment is recommended for individuals with PDH deficiency?

Answer 18

Reduced carbohydrates and increased fats in diet

Question 19

What glycolytic intermediates may be produced/consumed through the non-oxidative phase of the PPP?

Answer 19

Fructose-6-phosphote & Glyceraldehyde-3-phosphate

Question 20

What enzymes play an important role in the non-oxidative phase of the PPP?

Answer 20

Transketolase & Transaldolase

Question 21

What enzyme plays a role in both TCA and ETC?

Answer 21

Succinate dehydrogenase (Complex II)

Question 22

Where is the PDH complex located?

Answer 22

Mitochondrial matrix

Question 23

What molecules activate the PDH kinase?

Answer 23

CoA, ADP, pyruvate, & NAD+ activate the PDH kinase.

Question 24

What products are generated in the oxidative phase of the PPP?

Answer 24

NADPH & Ribulose-5-Phosphate

Question 25

This type of reaction utilizes TCA intermediates to synthesize other molecules.

Answer 25

Cataplerotic reaction

Question 26

Describe the process of PDH. Be sure to include relevant enzymes and cofactors.

Answer 26

Enzyme 1 attaches the acetyl group of pyruvate to TPP, releasing CO2. Enzyme 2 transfers the acetyl group from TPP to lipoic acid and then to CoA to form acetyl CoA. Enzyme 3 reoxidizes the lipoic acid using FAD to form FADH2. NAD+ is used to oxidize FADH2, producing NADH + H+.

Question 27

What molecules stimulate the PDH phosphatase? What is the result of phosphatase activity?

Answer 27

Mg2+ & Ca2+ - The phosphatase dephosphorylates the PDH complex, thereby activating it

Question 28

Pyruvate is produced via glycolysis in the cytosol. How is pyruvate transported to the mitochondria for PDH?

Answer 28

Pyruvate crosses the mitochondrial outer membrane via a voltage-dependent anion channel (VDAC) with inorganic phosphate. Pyruvate is then translocated into the mitochondrial matrix through a pyruvate symporter paired with a proton.

Question 29

What molecules directly activate PDH?

Answer 29

Pyruvate, CoA, & NAD+

Question 30

Flip for TCA cycle.

Answer 30

Question 31

How is the PPP regulated?

Answer 31

High levels of NADPH inhibit G6PDH. High levels of insulin favor the PPP.