Glycolysis Flashcards
(37 cards)
what is glucose?
the universal fuel for for human cells
what is the goal of glycolysis? its products?
to generate ATP and reducing equivalents from glucose; it generates 2 moles NADH and 2 moles APT per mole of glucose
what is glycolysis the pathway for?
oxidation of glucose to pyruvate
what are some cells that are dependent on glucose as fuel sources for ATP production?
red blood cells: lots of O2, but no mitochondria
brain cells: lots of O2 and mitochondria, but cells lack machinery to use fatty acids for fuel
*** fatty acids don’t cross the blood-brain barrier .
glycolysis produces precursors for these other pathways too?
pentose phosphate pathway
amino acid biosynthesis
Glycerol 3-phosphate forms the backbone for triglyceride synthesis
1,3-bisphosphoglycerate can be converted to 2,3-bisphosphoglycerate
which is an allosteric inhibitor of oxygen binding to Hb which
can be dephosphorylated to 3-phosphoglycerate and reenter glycolysis
T/F, pyruvate is the a product of glycolysis?if so, what is it a precursor for?
T, fatty acid synthesis
*A. Recognize the glycolytic pathway
Net ATP produced independent of TCA cycle (anaerobic ATP production).
NADH produced (reduced cofactor) which leads to ATP production in mito
End of glycolysis is formation of pyruvate
Pyruvate enters TCA cycle leading to Lots of ATP
*A. identify the two phases of the pathway
ATP Preparative phase
ATP generating phase
*A. define the two phases of the pathway
Glucose → pyruvate (NET 2ATP), 2 moles pyruvate per mole glucose net 2ATP
The Two phases
Preparative phase:
-This one uses 2 ATPs to get glucose phosphorylated on both ends of the molecule
-Activates the glucose molecule
-Cleavage of glucose into two triose phosphates
ATP-generating phase:
- Generates 4 ATP (substrate level phosphorylation) and 2 NADH molecules (glyceraldehyde 3-phosphate oxidation by NAD+ and phosphorylation by Pi)
- Rearrangement of phosphates into high energy bonds
where does glycolysis occur?
in the cytosol
what is one mole of glucose oxidized too?
one mole of glucose is oxidized to 2 moles of pyruvate
glycolysis has an overall net negative ΔGo’, which drives the pathway forward, T/F?
T
what happens when you do not have oxidized NAD+ for glycolysis?
glycolysis stops, you won’t have NADH and even ATP if ADP is absent
Glucose + 2 NAD+ (must be present to make ATP) + 2 Pi + 2 ADP ->
2 Pyruvate + 2 NADH + 4 H+ + 2 ATP + 2 H2O
*B.Define the role of NAD+/NADH in the glycolytic pathway
NAD+ is the oxidized precursor
NADH is the reduced cofactor
describe the total amount of ATP produced from aerobic cellular metabolism?
Pyruvate to Acetyl CoA produces one NADH molecule, and 2 pyruvates are made per one glucose: that contributes 5 ATP molecules. Because 2 acetyl CoA molecules enter the TCA Cycle and we get 9 ATP per single cycle, that’s 18 ATP. 2 net ATP molecules are produced by glycolysis directly. Together, that’s 25 molecules of ATP per single molecule of glucose
What is the first committed step of glycolysis?
Use of an ATP to drive reaction costs energy: must not be wasted
Phosphorylated glucose “trapped” in cell: cannot be transported back out
Highly negative ΔGo’ of reaction prevents reverse reaction
glucose 6-phosphate is a common intermediate for pathways that use glucose
key intersection point
allows for regulation of flux of glucose between pathways
in liver and pancreatic B cells, what is the enzyme that is used for phosphorylation?
glucokinase which has much lower affinity for glucose…higher Km for glucose
*G. Compare and contrast the function of hexokinase and glucokinase, in terms of the tissues where these two enzymes are found.
-Hexokinase and glucokinase (in liver) phosphorylate glucose to glucose 6-phosphate
-Glucokinase has a much lower affinity for glucose and higher Km for glucose
○ Glucose concentration must be much higher in these cells to activate phosphorylation (sigmoidal curve)
-Portal vein carries glucose from small intestine to liver
-High blood glucose drives glucose transport into hepatic cell
-As glucose accumulates in the cell, liver enzyme will start to phosphorylate glucose so the liver cells can use it
-Hexokinase has a greater affinity for oxygen (hyperbolic curve)
-Having just a cracker as a snack, the liver doesn’t care because it’s such a low amount of glucose
*E. Identify the glycolysis intermediates that are used by other pathways.
-1,3-bisphosphoglycerate can be converted into 2,3-bisphosphoglycerate
○ Modifies Hb
○ Allosteric inhibitor of oxygen binding to Hb
○ Can be dephosphorylated to 3-phosphoglycerate and reenter glycolysis
-Pyruvate is a precursor to FA synthesis
-Pentose phosphate pathway: ribose 5-phosphate= sugar for nucleotides
-Amino acid biosynthesis: Ser, Gly, Cys, Ala… AA catabolism produces glycolysis intermediates
Define the concept of a “committed step” in a pathway, using the conversion of glucose to glucose-6-phosphate as an example.
-A committed step is a step during the pathway where it can not go backward in the pathway
-Very high -deltaG
-Example: PFK-1 commits the pathway to stay in glycolysis by phosphorylating fructose 6-phosphate to fructose 1,6-bisphosphate
-Example: hexokinase phosphorylates glucose to glucose 6-phosphate, which activates glucose and traps it in the cell
○ Glucose 6-phosphate is not committed to glucose and can go to pentose phosphate pathway or glycogen synthesis
*H.Recognize why the action of phosphofructose-1 (PFK-1) is considered the committed step in glycolysis.
- PFK-1 phosphorylates fructose 6-phosphate to fructose 1,6-bisphosphate
- Due to the molecule having phosphate on both ends the molecule IS COMMITTED TO GLYCOLYSIS
- Irreversible
- Rate limiting step
this determines how glucose 6 phosphate it used, just because you are G6P does not mean you are committed
*M. What is the effect of patients with a PFK-1 deficiency?
In Red Blood Cells: RBCs can’t do glycolysis. As the only means of ATP production, the RBCs can’t survive without PFK-1…hemolytic anemia!
In Skeletal Muscle: Skeletal muscle can’t generate sufficient ATP from glycolysis to meet energy needs. Leads to cramps and muscle weakness.
*I.Recognize the effects of AMP versus ATP on PFK-1 activity.
- AMP and fructose 2,6-bisphosphate both activate PFK-1
- ATP inhibits: need ATP to make forward rxn work, when ATP builds up, it shuts down the enzyme negative modulator
*J. Define the function of the malate/aspartate and glycerol-3-phosphate shuttles for exchanging NADH / NAD+ reducing equivalents across the inner mitochondrial membrane.
-Glycerol 3-P Shuttle
○ Glucose → pyruvate gives off a NADH + H+
○ An electron is taken from NADH to help oxidize dihydroxyacetone-P → glycerol 3-P
○ Electron from the glycerol 3-P is taken to reduce FAD → FADH2
○ That FADH2 will get put into the ETC via CoQ (complex 1,2,3)
○ Leads to the production of 1.5 ATP per mole of NADH
-Malate-Aspartate Shuttle
○ -deltaG
○ Takes an NADH molecule to help the reaction of oxaloacetate → malate
○ Make NADH in cytosol and regenerate NADH in the mitochondria
○ Players: malare, OAA, aKG (TCA)
○ NADH is regenerated, so 2.5 mol ATP can be produced (1 mol NADH → 2.5 mol ATP in ETC)
