Chapter #16: Glycolysis Flashcards
Give a general overview of glycolysis
Glycolysis…
* takes place in the cytoplasm of the cell
* does not require oxygen
* consumes some ATP
* generates some ATP
* produces net ATP
* produces net NADH
Because the process of glycolysis is anaerobic, it is though to be an ancient pathway that developed before substantial amounts of oxygen were present in the atmosphere.
What happens in Stage 1 of glycolysis?
Conversion of glucose into fructose 1,6-bisphosphate
Reactions:
*Phosphorylation #1
*Isomerization
*Phosphorylation #2
What’s the point?
* Trap glucose in the cell and form a compound of higher energy that can be readily cleaved into phosphorylated three-carbon units.
What happens in step 1 of Glycolysis: Stage 1 and the goals of this step?
- Phosphorylate glucose to form glucose 6-phosphate
Goals of this step:
* Traps glucose in the cell
* Destabilizes glucose for further reactions
* Adds an irreversible step at the start of the pathway for potential regulation
What happens in step 2 of Glycolysis: Stage 1 and the goals of this step?
- Isomerize glucose 6-phosphate to fructose 6-phosphate
Goals of this step:
* Moves the carbonyl (reactive) toward the center of the molecule (aldose to ketose conversion) so it can be split in half
* Prevents the need for two pathways (2-C & 4-C)
What happens in step 3 of Glycolysis: Stage 1 and the goals of this step?
- Phosphorylate fructose 6-phosphate to form fructose 1,6-bis phosphate
Goals of this step:
* Sets up the molecule so it can be split into a pair of three-carbon molecules, which BOTH contain phosphate for subsequent reactivity
* A second irreversible step in the pathway that can be used for regulation.
Describe Glycolysis Stage 2
Conversion of fructose 1,6-bisphosphate into two molecules of glyceraldehyde 3-phosphate
Reactions
*Aldol cleavage
*Isomerization
Goal of this step:
* Create three-carbon molecules that can be readily converted to pyruvate
What happens in step 4 of Glycolysis: Stage 2 and the goals of this step?
- Fructose 1,6-bis phosphate is split into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate
Goal of this step: * Produces three-carbon molecules that can be converted to pyruvate Note: The enzyme name is derived from the reverse reaction, an aldol (aldehyde + alcohol) condensation.
Describe Glycolysis Stage 3
Glyceraldehyde 3-phosphate is converted to pyruvate
Reactions
*Oxidation/phosphorylation
*Dephosphorylation
*Intramolecular phosphate shift
*Dehydration
*Dephosphorylation
Goal of this step:
* Pyruvate is formed for further catabolism, while net ATP and NADH are generated
What happens during *Oxidation/phosphorylation *Dephosphorylation of stage 3 glycolysis
What happens during *Oxidation/phosphorylation *Dephosphorylation *Intramolecular phosphate shift *Dehydration *Dephosphorylation of glycolysis stage 3
What happens in step 10 of Glycolysis: Stage 3 and the goals of this step?
- Phosphoenolpyruvate is converted to pyruvate
Goals of this step:
* ATP is formed to produce a net gain of 2 ATP molecules
* Another irreversible reaction that can serve as a point of regulation
* Pyruvate is formed for subsequent use
What is the overall reaction of glucose to pyruvate under anaerobic conditions?
*There is a net production of 2 ATP molecules
*There is net production of 2 NADH molecules
*Approximately 96 kJ/mol of energy is released
*Redox is not yet balanced!
If nothing is done, the catalytic amounts of NAD+ will remain tied up as NADH and there will be no NAD+ to continue glycolysis!
What are irreversible reactions?
They are involved in the regulation of glycolysis (hexokinase, phosphofructokinase, pyruvate kinase)
“Irreversible reactions”
These reactions are regulated by reversible allosteric control (very fast – millisecond response time)
What is the role of glycolysis in muscle?
*Powers contraction
What is the control of glycolysis in the liver?
- Store glucose as glycogen
- Release glucose into blood
- Generate reducing power for biosynthesis
- Synthesize biochemicals
How is glycolysis regulated in muscle?
- A key point to remember about muscles is that energy charge has primary control over glycolysis.
- Energy charge, in simplest terms, is the ratio of ATP/AMP or ATP/ADP.
- Muscles are only concerned with whether they have enough ATP to power their contraction, so their regulation of glycolysis is relatively simple compared to the liver.
How is hexokinase help the regulation of glycolysis in muscle?
Hexokinase (in muscle)
*Inhibited by product G6P Thus, hexokinase is inhibited when phosphofructokinase is inhibited, because F6P builds up, causing G6P to build up.
How is Phosphofructokinase help the regulation of glycolysis in muscle?
Phosphofructokinase (in muscle)
* Activity is inhibited by high levels of ATP. Plenty of energy supply, don’t burn glucose and make more! (Affinity for F6P is lowered)
- Activity is enhanced by high levels of AMP and ADP. Energy supply is low, burn glucose and make more ATP! (Reverses the action of ATP)
- Activity is inhibited by low pH. pH is dropping fast under the current metabolic conditions – slow down glycolysis! (This is the most important site of control in the mammalian glycolytic pathway!)
What is the first irreversible reaction unique to glycolysis?
The formation of F-1,6BP is the first irreversible reaction unique to glycolysis
The committed step
How is Pyruvate kinase help the regulation of glycolysis in muscle?
Pyruvate kinase (in muscle)
- Activity is inhibited by high levels of ATP. Just like with phosphofructokinase – energy charge is high, don’t burn glucose and make more!
- Activity is enhanced by AMP. Energy supply is low, burn glucose and make more ATP!
- Activity is enhanced by F-1, 6-BP. Glycolysis products are coming your way!
- Activity is inhibited by alanine. We’ve got plenty of material for biosynthesis – don’t waste your pyruvate on our account!
- Activity is inhibited by acetyl CoA. We’ve got plenty of material for biosynthesis – don’t waste your pyruvate on our account!
Describe the regulation of glycolysis in muscle (picture)
How does hexokinase regulate glycolysis in the liver?
Hexokinase (in liver)
- Remember that unlike muscle, the liver is responsible for a lot more than just itself. The liver needs to:
- Store glucose as glycogen
- Release glucose into blood
- Generate reducing power for biosynthesis
- Synthesize biochemicals
*Inhibited by product G6P But, there is also a specialized isozyme of hexokinase in the liver called glucokinase
*NOT inhibited by G-6P
*50-fold lower affinity for glucose
Why have glucokinase in the liver?
Low affinity means that G-6P is made in the liver only when glucose is abundant. The liver will then use G-6P for NADPH formation via PPP and glycogen synthesis. The liver won’t steal glucose in times of need.
How does Phosphofructokinase regulate glycolysis in the liver?
Phosphofructokinase (in liver)
Just like in muscle you have
*ATP decreasing
*AMP/ADP increasing
*pH (not really a factor)
Activity is inhibited by citrate in conjunction with ATP. We’ve got plenty of biosynthetic precursors in the citric acid cycle – slow down with glycolysis!
Activity is enhanced by fructose 2,6-bisphosphate. Glucose and fructose are high, let’s store some energy.
What is F2,6BP?
F2,6BP is a measure of blood glucose levels
How does Pyruvate kinase regulate glycolysis in the liver?
Just like in muscle you have
*ATP decreases
*AMP increases
*F-1, 6-BP increases
*Alanine decreases
*Acetyl CoA decreases
Activity in the liver is also regulated by the presence of the “L” isozyme of pyruvate kinase, which is inhibited by signal transduction when glucose is low. Don’t steal the sparse glucose from brain and muscle!
Low blood glucose levels mean that glucagon is present, activating the cAMP cascade, phosphorylating pyruvate kinase, and creating a less active enzyme.
How do you restore the redox balance?
Describe lactate fermentation
Describe ethanol fermentation
Describe glycolysis under anaerobic conditions when the redox is balanced
What is the take home message for glycolysis?
- The glycolysis is an evolutionarily conserved pathway.
- The glycolysis has 10 steps, with three irreversible reactions that regulate this pathway.
- Regulation of glycolysis depends on the tissue.
- From one molecule of glucose (6C), two pyruvate molecules (3C) are generated, as well as two ATP (net production) and two NADH.
- The redox balance is ensured by other pathways: fermentation in the absence of oxygen and the electron transport chain in presence of oxygen.
