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Biochemistry PMY-3 > Glycolysis 2 > Flashcards

Glycolysis 2 Flashcards

1
Q

What are the key features of glycolysis?

A
  • Oxidation of glucose to 2 molecules of Pyruvate
  • Cytosolic pathway
  • three irreversible reactions(regulatory steps)
    - Glucokinase/Hexokinase
    - Phosphofructokinase-1
    - Pyruvate kinase

Two substrate level phosphorylation reactions

   - Phosphoglycerate kinase
   - Pyruvate kinase
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2
Q

What effect does insulin have in glycolysis?

A

Insulin up-regulates the 3 rate limiting enzymes in glycolysis

  • Glucokinase/Hexokinase
  • Phosphofructokinase
  • Pyruvate kinase
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3
Q

What is the effect of glucagon on glycolysis?

A

Down regulates the 3 rate limiting steps of glycolysis

  • Glucokinase/Hexokinase
  • Phosphofructokinase
  • Pyruvate kinase
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4
Q

pat what steps are glycolysis regulated ?

A

The 3 irreversible steps and by transport of glucose in the cell

  • GLUT 4 regulated by insulin( muscle, adipocytes)
  • Formation of glucose 6-phosphate (Glucokinase/Hexokinase)
  • formation of fructose-1,6 bisP(PFK-1)
    - main regulatory point

-Regulation of Pyruvate kinase

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5
Q

What is normal blood glucose level?

A

Normal blood glucose level around 4.5 Mm, but may increase after a meal

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6
Q

Describe the chemical behavior of Glucokinase

A
  • Km ~ 10Mm(HIGH)
  • Liver, B-cells of pancreas
  • NOT inhibited by glucose 6-P
  • Liver uses blood glucose after a meal
  • B-cells act as glucose sensor
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7
Q

Describe the chemical behavior of Hexokinase

A
  • Km~0.1 Mm (LOW)
  • Insulin responsive peripheral tissues(muscle)
  • Muscle and adipose only take glucose when blood glucose is high(GLUT-4).
  • Inhibited by Glucose 6-P
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8
Q

What is PFK-1 inhibited by?

A
  • ATP (in muscle)

- Citrate

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9
Q

What chemicals activates PFK-1?

A

Activated by:

AMP(in muscle )

Fructose-2,6-bid-P —> affects substrate a

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10
Q

What hormones regulate PFK-1?

A

Insulin and glucagon

-Fructose-2,6-his-P levels regulate glycolysis

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11
Q

Highlight hormonal regulation of glycolysis in a well fed state

A

Insulin dephosphorylates FBP-2/PFK-2(bifunctional enzyme ) thereby activating PFK-2 activity.

PFK-2 converts fructose 6-P to fructose 2,6-BP.

This leads to activation of PFK-1 and enhances glycolysis

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12
Q

Highlight glycolysis hormonal regulation in a fasting state

A

Glucagon activates protein kinase A which phosphorylates FBP-2/PFK-2 activity. This results in the conversion of fructose 2,6-BP back to fructose 6-P. Glycolysis is inhibited

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13
Q

What is the function of PFK-2?

A

PFK-2 forms 2,6 bisphosphate(not a substrate of glycolysis; but a regulator of glycolysis)

Fructose 2,6-bisphosphate is a potent regulator of PFK-1

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14
Q

Explain the regulation of Pyruvate kinase

A
  • Inhibited by ATP and Acetyl-CoA
    • High energy intermediate (ATP)
    • Abundent fuel from FA oxidation (Acetyl-CoA)
  • Activated by AMP
    • Low energy signal
  • Activated by fructose-1,6-bisphosphate
    - Feed forward mechanism from committed step
  • Glucagon —> leads to covalent phosphorylation by a protein kinase A
    • Inhibition of Pyruvate kinase(liver only)
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15
Q

Does Glucose 6-P inhibit Glucokinase?

A

No

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16
Q

What are the major fates of Pyruvate?

A

4 major fates in humans

a. Acetyl CoA
b. Oxaloacetate
c. Ethanol(microorganism)
d. Lactate
e. Alanine

17
Q

The fate of Pyruvate depends on__________

A

Oxygen availability

18
Q

What happens to pyruvate in anaerobic conditions?

A

No mitochondria and less oxygen

Pyruvate —> lactate(lactate dehydrogenase)

Reoxidizes the NADH to allow glycolysis to proceed

19
Q

What happens to pyruvate in aerobic conditions?

A

Aerobic conditions (oxygen and mitochondria)

  • a Pyruvate is transported into the mitochondria by Pyruvate dehydrogenase complex(PDH complex)
  • NADH is also reoxidized in the mitochondria(shuttle pathway allows NADH equivalents to enter mitochondria)
20
Q

Describe the chemical reaction of lactate reduction

A

During anaerobic glycolysis, Pyruvate is converted to lactate to regenerate NAD+

Pyruvate converted to lactate
Enzyme: lactate dehydrogenase

This converts to NADH, and a proton to NAD+

Regenerated NAD+ is now free to participate in the Glyceraldehyde-3-P-dehydrogenase reaction

21
Q

The conversion of Pyruvate to lactate is reversible, what does the direction of the reaction depend on?

A

The direction of the reaction ( Pyruvate to lactate(and vice versa) ) depends on NADH/NAD+ ratio. Higher the NADH levels, the reaction is driven towards lactate formation

22
Q

What is hemolytic anemia?

A
  • Erythrocyte Pyruvate kinase deficiency
  • Mature RBCs lack mitochondria and are completely dependent on glycolysis for ATP formation
  • defects in glycolysis would result in hemolysis and hemolytic anemia due to decreased ATP generation
23
Q

Describe the fate of lactate in anaerobic glycolysis

A

-Lactate formed in muscle and red blood cells, eventually diffuses out of the cells and is taken to the liver where it is used for gluconeogenesis

24
Q

What causes cramps during exercise?

A

Lactate accumulation in muscle causes a drop in pH and may manifest as cramps during intense exercise

25
Q

Why do alcoholics suffer lactic acidosis?

A

In alcoholics; increase in NADH due to ethanol metabolism leads to lactic acidosis

26
Q

Where does lactate often form?

A

In an actively contracting skeletal muscle, NADH formed as a result of glycolysis, exceeds to oxidative capacity of the ETC(Low oxygen tension), resulting in a high NADH/NAD+ ratio. This favors the conversion of Pyruvate to lactate via lactate dehydrogenase

Biochemistry PMY-3 (37 decks)

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