Lecture 6 Flashcards
What is the overall reaction starting from glucose to acetyl-CoA?
Glucose -> glycolysis; 2NADH and 2 ATP net yield -> pyruvate -> acetyl-CoA
What are the 3 irreversible reactions in glycolysis?
- Glucose to glucose 6-P by hexokinase or glucokinase
- Fructose 6-P to fructose 1,6-BP by PFK-1
- PEP to pyruvate by pyruvate kinase
What is another irreversible step not typically included in the big three? Why is it irreversible?
Step 7, where 1,3-BPG converts into 2,3-PG by phosphoglycerate kinase.
It’s irreversible because it’s produces 2ATP
What it is priming phase of glycolysis? Which steps are those?
The first 5 steps are the priming phase, which contains 2 priming reactions: Glucose to Glucose 6-P and fructose 6-P to fructose 1,6-BP. The goal is to turn glucose to glyceraldehyde 3-P
What do the two priming reactions have in common?
They’re irreversible and use up ATP
Why is step 6 the start of the “payoff phase?”
The conversion of glyceraldehyde 3-P to 1,3-BPG finally yields 2NADH. Then 1,3-BPG to 2,3-PG yields 2ATP. The conversion of PEP to pyruvate yields 2ATP.
At which step is the 6-carbon sugar cleaved into a 3-carbon sugar?
Step 4, where fructose 1,6-BP cleaves into glyceraldehyde 3-P and DHAP
What’s the chemical logic behind phosphorylating glucose in step 1?
We want a concentration gradient that favors glucose import, so we phosphorylate it so that it doesn’t count as glucose anymore. This keeps the concentration of glucose in the cell low. Also, there aren’t glucose 6-P transporters either
What’s the chemical logic behind step 2 in glycolysis?
Isomerization moves switches the C-1 carbonyl with the C-2 OH, a prerequisite for steps 3 and 4. We want to be able to phosphorylate both sides of the sugar to yield symmetry for when the product splits into a 3-carbon sugar.
The placement of the C-2 carbonyl helps facilitate a retro-Aldol reaction to yield DHAP and glyceraldehyde 3-P
What is the chemical logic behind step 6?
This is when glyceraldehyde 3-P gets phosphorylate to 1,3-BPG, thus producing 1NADH. This is required to make ATP in step 7
What’s the chemical logic behind step 8?
The last phosphate group moves from C-2 to C-3, which sets up for a dehydration reaction that will activate the phosphoryl group in what is now PEP. It will then be transferred over to ADP to make 1 ATP. This makes pyruvate.
Why do 1,3 BPG and PEP (in steps 7 and 10, respectively) have high phosphate transfer potential?
1,3-BPG has a resonance-stabilized product and PEP tautomerizes to its stabler keto form of pyruvate. Thus, their phosphate transfers result in large delta Gs, which sums with ATP synthesis for a net negative deltaG.
Explain the allosteric regulation of PFK-1
ATP is the main substrate, but it also allosterically inhibits PFK-1. When ATP is low and ADP + Pi are high, PFK-1 is high since more energy is needed
When ATP is high and ADP +Pi are low, PFK-1 is low since the cell has enough energy
What are feeder pathways into glycolysis?
Lactose, sucrose, glycogen, and starch
How does fructose bypass the major PFK-1 regulatory step?
It converts fructose 1-P to glyceraldehyde and DHAP, both of which can be directly converted into glyceraldehyde 3-P. This intermediate shows up after the PFK-1 regulatory step such that it can quickly turn into acetyl-CoA and then fatty acids/fats
