PPP, PDH, & TCA Cycle Flashcards
What is the effect of a buildup of high energy molecules on TCA?
A buildup or NADH and ATP indicate the cell has adequate energy. TCA will be inhibited.
G6PDH deficiency is the most common enzyme defect. How else may G6PDH deficiency be caused?
Consumption of uncooked fava beans
What energy molecules are generated through TCA? How?
Oxidative Phosphorylation - 3 NADH, 1 FAHD2
Substrate-level phosphorylation - 1 GTP
What molecules directly inhibit PDH?
Acetyl CoA & NADH (products of the complex)
Where does the PPP take place?
Cytoplasm
What are the two phases of the PPP? Are they reversible or irreversible?
Oxidative - Irreversible
Non-oxidative - Reversible
What is the main enzyme involved in the oxidative phase of the PPP?
Glucose-6-Phosphate Dehydrogenase (G6PDH)
PDH activity can be regulated directly by its substrates and products. How else can PDH activity be regulated?
Phosphorylation by the PDH kinase inhibits the complex. Dephosphorylation by the PDH phosphatase activates the complex.
What is the rate-limiting step of TCA?
Isocitrate –> alpha-ketoglutarate via isocitrate dehydrogenase
What enzymes regulate TCA?
Citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase
What cofactors are necessary for PDH?
Thiamine/TPP (B1), Lipoic Acid, CoA (B5), FAD (B2), NAD+(B3),
What is the effect of AMP and Ca2+ on TCA?
AMP and CA2+ indicate the cell is in need of energy. These molecules will stimulate TCA by activating the alpha-ketoglutarate dehydrogenase.
What is the composition of the PDH complex?
A complex of 5 enzymes in the mitochondrial matrix that forms acetyl Co-A from pyruvate
What is the effect of PDH deficiency?
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.
What is the commitment step of TCA?
Acetyl-CoA –> Citrate via the citrate synthetase
This type of reaction synthesizes and replenishes intermediates of TCA.
Anaplerotic reaction
What is the significance of G6PDH deficiency?
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.
What treatment is recommended for individuals with PDH deficiency?
Reduced carbohydrates and increased fats in diet
What glycolytic intermediates may be produced/consumed through the non-oxidative phase of the PPP?
Fructose-6-phosphote & Glyceraldehyde-3-phosphate
What enzymes play an important role in the non-oxidative phase of the PPP?
Transketolase & Transaldolase
What enzyme plays a role in both TCA and ETC?
Succinate dehydrogenase (Complex II)
Where is the PDH complex located?
Mitochondrial matrix
What molecules activate the PDH kinase?
CoA, ADP, pyruvate, & NAD+ activate the PDH kinase.
What products are generated in the oxidative phase of the PPP?
NADPH & Ribulose-5-Phosphate
This type of reaction utilizes TCA intermediates to synthesize other molecules.
Cataplerotic reaction
Describe the process of PDH. Be sure to include relevant enzymes and cofactors.
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+.
What molecules stimulate the PDH phosphatase? What is the result of phosphatase activity?
Mg2+ & Ca2+ - The phosphatase dephosphorylates the PDH complex, thereby activating it
Pyruvate is produced via glycolysis in the cytosol. How is pyruvate transported to the mitochondria for PDH?
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.
What molecules directly activate PDH?
Pyruvate, CoA, & NAD+
Flip for TCA cycle.
How is the PPP regulated?
High levels of NADPH inhibit G6PDH. High levels of insulin favor the PPP.
