Glycolysis Flashcards

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1
Q

What are the four glucose transporters?

A
  • GLUT1
  • GLUT2
  • GLUT3
  • GLUT4
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2
Q

GLUT2

A
  • low-affinity transported in hepatocytes (liver cells) and pancreatic cells (specifically on the beta-islet cells)
  • capture excess glucose for storage
  • high Km
  • can’t be saturated under normal physiological conditions
  • not responsive to insulin but serves as glucose sensor to cause release of insulin in pancreatic beta-cells
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3
Q

GLUT4

A
  • present in adipose and muscle tissue
  • Km is low and close to normal glucose levels in blood so the transporter is saturated when blood glucose levels are slightly elevated compared to normal
  • transport rate increases when insulin level increases
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4
Q

What is the role glucose plays in adipose tissue?

A

glucose is required to form DHAP which is converted to glycerol phosphate to store incoming fatty acids as triacylglycerols

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5
Q

Glycolysis

A
  • carried out by all cells in their cytoplasm
  • the only energy-yielding pathway for red blood cells
  • does not require presence of oxygen
  • converts glucose molecule into 2 pyruvate molecules, releasing energy captured in two substrate-level phosphorylations and one oxidation reaction
  • 2 NADH from glycolysis typically leads to 3 ATP, giving this process a total of 5 ATP produced
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6
Q

What monosaccharides can enter glycolysis pathway?

A
  • glucose
  • galactose
  • fructose
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7
Q

List the enzymes used in glycolysis in order (10)

A
  1. Hexokinase (or if in liver/pancreas then Glucokinase)
  2. Phosphoglucose Isomerase
  3. Phosphofructose Kinase
  4. Fructose Bisphosphate Aldose
    (5. Triose Phosphate Isomerase)
  5. Glyceraldehyde 3-Phosphate Dehydrogenase
  6. Phosphoglycerate Kinase
  7. Phosphoglycerate Mutase
  8. Enolase
  9. Pyruvate Kinase
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8
Q

Which enzymes are irreversible?

A
  • How Glycolysis Pushes Forward the Process: Kinases*
  • Hexokinase
  • Glucokinase
  • PFK-1
  • Pyruvate Kinase
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9
Q

Hexokinase

A
  • phosphorylates glucose to form glucose 6-phosphate
  • requires ATP input
  • “traps” glucose in cell
  • inhibitor: glucose 6-phosphate
  • activator: AMP/ADP
  • irreversible
  • low Km [reaches max velocity at low concentrations of glucose]
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10
Q

Glucokinase

A
  • phosphorylates glucose to form glucose 6-phosphate
  • requires ATP input
  • “traps” glucose in cell
  • only found in liver cells and pancreatic beta-islet cells
  • irreversible
  • high Km [low affinity for glucose so requires high concentrations of glucose to achieve Vmax]
  • responsive to insulin in liver
  • induced by insulin
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11
Q

Phosphofructokinase-1 (PFK-1)

A
  • allosteric enzyme that regulates the pace of glycolysis
  • rate-limiting enzyme
  • phosphorylates fructose 6-phosphate to fructose 1,6-bisphosphate
  • requires ATP input
  • irreversible
  • inhibitors: ATP, citrate, glucagon
  • activators: AMP, fructose 2,6-bisphosphate, insulin
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12
Q

Phosphofructokinase-2 (PFK-2)

A
  • produces the fructose 2,6-bisphosphate that activates PFK-1
  • mostly found in liver
  • allows cells to over-ride inhibition caused by ATP so glycolysis can continue
  • inhibitors: glucagon
  • activators: insulin `
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13
Q

Glyceraldehyde-3-Phosphate Dehydrogenase

A
  • dehydrogenates glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate
  • during this reaction, NAD+ is reduced to NADH (oxidation) which is coupled to the phosphorylation of the substrate to form the 1,3-bisphosphoglycerate product
  • reversible rxn
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14
Q

3-Phosphoglycerate Kinase

A
  • substrate level phosphorylation – transfers phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate
  • step produces 2 ATP/ glucose
  • reversible rxn that does not depend on oxygen so is only source of ATP in ANAEROBIC tissue
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15
Q

Pyruvate Kinase

A
  • final enzyme in AEROBIC glycolysis
  • catalyzes substrate-level phosphorylation of ADP using substrate phosphoenolpyruvate (PEP)
  • activated by fructose 1,6 bisphosphate from PFK-1 rxn (this is example of feed-forward activation because product of earlier reaction stimulates a later rxn)
  • activators: fructose 1,6 bisphosphate, AMP/ADP
  • inhibitors: ATP, acetyl-CoA, Alanine
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16
Q

Glycolysis Net Reaction:

A

Glucose + 2 NAD+ + 2 Pi + 2 ADP = 2 pyruvate + 2 ATP + 2 NADH + 2 H2O

17
Q

What happens to pyruvate in the presence of O2?

A

it is further oxidized to CO2

18
Q

What happens to pyruvate in the absence of O2?

A

it can be fermented to lactate or ethanol

19
Q

Fermentation

A
  • occurs after glycolysis when oxygen is absent (anaerobic conditions)
  • occurs in cytoplasm of cell
  • prevents glycolysis from stopping by reducing pyruvate to lactate and oxidizing NADH to NAD+ via lactate dehydrogenase
  • key enzyme: lactate dehydrogenase
20
Q

Lactate Dehydrogenase

A
  • important enzyme in fermentation

- oxidizes NADH to NAD+, replenishing the oxidized coenzyme for glyceraldehyde-3-phosphate dehydrogenase

21
Q

What is the only pathway for ATP production in erythrocytes (RBCs)?

A

anaerobic glycolysis – yields a net 2 ATP / glucose

22
Q

Bisphosphoglycerate Mutase

A
  • enzyme present in RBCs-

- produces 2,3-bisphosphoglycerate from glycolysis molecule 1,3-bisphosphoglycerate

23
Q

Explain the relationship between 2,3-Bisphosphoglycerate (2,3-BPG) and Hemoglobin

A
  • 2,3-BPG binds allosterically to the beta chains of Hemoglobin A and decreases its affinity for oxygen
  • leads to a rightward shift (Bohr Shift) in Hb dissociation curve, making O2 unloading at tissues easier while still allowing 100% saturation in lungs
24
Q

What conditions shift Hb dissociation curve right?

A
  • increased CO2
  • increased H+ concentration (same as decreased pH)
  • increased temperature
  • increase in 2,3-BPG
25
Q

What does a leftward shift in the Hb curve signify?

A
  • increased Hb affinity for O2

- decreased O2 unloading at tissues

26
Q

What conditions shift Hb dissociation curve left?

A
  • decreased CO2
  • decreased H+ concentration (same as increased pH)
  • decreased temperature
  • decrease in 2-3-BPG
27
Q

Fetal Hemoglobin (HbF)

A
  • has increased affinity for O2 which allows for transplacental passage of O2 from mother to infant
  • causes a leftward shift in Hb dissociation curve
  • 2,3-BPG does not bind well to HbF
28
Q

Pyruvate Dehydrogenase Complex

A
  • complex that pyruvate products from glycolysis enter under aerobic conditions
  • irreversible
  • in the liver it is activated by insulin
  • converts pyruvate to acetyl Co-A via enzyme pyruvate dehydrogenase (PDH), which also produces NADH and CO2
  • complex requires: thiamine pyrophosphate, lipoic acid, CoA, FAD, NAD+
  • inhibitors: acetyl CoA
29
Q

What are the two enzymes that regulate PDC?

A
  • Pyruvate Dehydrogenase Kinase

- Pyruvate Dehydrogenase Phosphatase

30
Q

Pyruvate Dehydrogenase Kinase

A
  • enzyme that phosphorylates PDH thus inhibiting acetyl-CoA production from pyruvate
  • activators: ATP, acetyl-CoA, NADH
31
Q

Pyruvate Dehydrogenase Phosphatase

A
  • enzyme that removes a phosphate from PDH which activates acetyl-CoA production from pyruvate
  • activators: ADP, NAD+, pyruvate
32
Q

What are the products of PDC (from one glucose)?

A

2 CO2 and 2 NADH

33
Q

How many ATP could be produced from PDC (from one glucose)?

A

5 ATP

34
Q

What are the 3 possible fates of pyruvate?

A
  • conversion to acetyl CoA by pyruvate dehydrogenase
  • conversion to lactate by lactate dehydrogenase (fermentation)
  • conversion to oxaloacetate by pyruvate carboxylase (gluconeogenesis)