Week 5: Glycolysis and the PPP Flashcards
What are the starting materials of glycolysis? What other input is required in the priming phase?
Glucose, 2 ADP, 2Pi, 2 NAD+
2 ATP are required to create G-6-P and F-1,6-BP respectively
What are the products of glycolysis?
2 Pyruvate, 4 ATP, 2 H+, 2 NADH, 2 H20
What are the glycolysis intermediates and how do we remember them?
**Goodness = Glucose
Gracious = G-6-P
**Father = Fructose-6-P
*Franklin = Fructose-1,6-Bisphosphate
Did = Dihydroxyacetone Phosphate (DHAP)
*Go = Glyceraldehyde-3-Phosphate
*By = 1,3-Bisphosphoglycerate
Picking = 3-Phosphoglycerate
Pumpkins = 2-Phosphoglycerate
to
Prepare = Phosphoenolpyruvate
**Pies = Pyruvate
* = key steps, reversible and
** = key steps, irreversible
What are the glycolysis enzymes and how do we remember them?
Hungry = Hexokinase
Peter = Phosphohexose Isomerase
Pan = PFK-1
And = Aldolase
The = Triose Phosphate Isomerase
Growling = G3P Dehydrogenase
Pink = Phosphoglycerate kinase
Panther = Phosphoglycerate mutase
Eat = Enolase
Pies = Pyruvate kinase
What are the ways that we can regenerate NAD+
Aerobically in mitochondria: 2 NADH + 2H+ + O2 => 2 NAD+ + 2H2O
Anaerobically in the cytosol: Pyruvate + 2 NADH + 2H+ => L-lactate + 2 NAD+
What are the main purposes of the PPP?
(1) To produce NADPH + H+ from NADP+
(2) to synthesize ribose-5-phosphate for biosynthesis
What does the carbohydrate product of the PPP feed into?
The ribose-5-phosphate from the PPP feeds into the de novo nucleotide biosynthesis pathway, and is converted to PRPP by PRPP synthetase, then to 5-phosphoribosylamine by glutamine-PRPP amidotransferase
What is the key step of the PPP and why is it important?
The G-6-P dehydrogenase enzyme (first step) converts NADP+ to NADPH + H+ a
What are the two phases of the PPP and why are they important?
(1) The oxidative phase converts G-6-P to 2 NADPH + 2 H+, and the…
(2) Nonoxidative phase uses transketolases/transaldolases to return unused ribulose-5-phosphate to G-6-P
What is NADPH used for? What is the main point of this process, and what cells in the body use it in particular?
It is used as a reducing cofactor for the glutathione reductase reaction, reducing oxidized glutathione molecules (GSSG) to 2 GSH molecules
This is a key means by which the body reduces reactive oxygen species (ROS). The RBCs of the body use this mechanism because they don’t have mitochondria that would help them neutralize ROS otherwise.
Explain how favism relates to the PPP
Favism is the result of a deficiency in G-6-P dehydrogenase, leading to a lack of NADPH to reduce ROS. If patients with this disease eat fava beans, the metabolites can produce dangerous superoxide radicals and H2O2 (hydrogen peroxide) that can damage tissues and cells–especially RBCs.
Why is step 1 of glycolysis significant in terms of (1) thermodynamics and (2) biochemical pathways?
(1) Large, -ΔG due to the energy released from ATP bond severing, large -ΔH
(2) Phosporylating glucose traps it in the cell, and prevents it from traveling outwards through GLUT transporters. Further, G-6-P can enter other pathways including the PPP.
Why is step 3 of glycolysis significant in terms of (1) thermodynamics and (2) the glycolysis pathway? What allosteric regulators are involved, and (3) what is the extra-glycolytic molecule that helps regulate it?
(1) Large, -ΔG due to the energy released from ATP bond severing, large -ΔH, IRREVERSIBLE
(2) This is a regulatory step of glycolysis–ATP will inhibit PFK-1 and ADP/AMP and citrate will activate it (conveys need for acetyl-CoA)
(3) fructose 2,6-bisphosphate is synthesized from high amounts of fructose-6-phosphate. Fructose 2,6-bisphosphate allosterically activates PFK-1 because it acts as a proxy, telling PFK-1 there’s lots of F-6-P around to use
Why is step 4 of the glycolysis pathway significant thermodynamically (1), what does it produce as intermediates (2), and why does it move forward (3)?
(1) There is a large +ΔG required to break the bonds of the F 1,6-BP molecule, but Le Chatelier prevails!
(2) G3P is made and keeps moving through the glycolytic pathway, and DHAP can be converted by triose phosphate isomerase OR shunted into the FA pathway to serve as a substrate for TAG production
(3) Because the G3P products of the reaction are removed so quickly, the reaction continues moving forward despite a +ΔG
Why is step 6 of glycolysis significant and reversible (1)? What drives the reaction forward (2) and why is ΔG not negative (3)?
(1) this step adds another INORGANIC phosphate group to G3P, and uses the high energy generated from severing the aldehyde bond to produce NADH
(2) Renewal of NAD+ substrate to be reduced to NADH drives the reaction forward
(3) IF the phosphate group were added via ATP bond-breaking, this reaction would likely be irreversible. HOWEVER, an inorganic phosphate is added, demanding some energy and creating a +ΔG
Explain the different ways glycolysis proceeds under aerobic and anaerobic conditions
Under aerobic conditions, 2 NADH, 2 H+ along with O2 from breathing use electrons to pump H+ ions across the mitochondrial membrane. 2 NAD+ are regenerated via oxidative mechanisms.
Under anaerobic conditions, NAD+ is regenerated from NADH by reducing pyruvate to L-Lactate in a highly favorable reaction catalyzed by lactate dehydrogenase. The majore disadvantage is that NADH cannot send its high-energy electrons through the ETC, and though the reaction proceeds very quickly/explosively, the low ATP yield via lactate fermentation cannot be sustained for long.
