Glycolysis Flashcards

1
Q

What are the two enzymes that convert glucose to glucose-6-phosphate?

A
  1. Hexokinase
  2. Glucokinase
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2
Q

What does Hexokinase do?

A
  • high affinity (low KM) but low capacity (low VM)
  • found in most tissues
  • inhibited by glucose-6-phosphate/not induced by insulin
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3
Q

What does glucokinase do?

A
  • low affinity (high KM) but high capacity (high VM)
  • found in the liver and β-cells
  • NOT inhibited by glucose-6-phosphate/induced by insulin
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4
Q

Describe production of 2,3BPG

A
  • Bypass of 1,3BPG to 3PG, step makes 2ATP
  • side reaction of glycolysis
  • important in RBC (binding or 2,3BPG stabilizes the deoxy form, facilitates release delivery of oxygen to the tissues)
  • reduces net production of glycolysis by 1 ATP when made
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5
Q

What are the 3 irreversible steps of regulation for glycolysis?

A
  • Glucose to Glucose-6-Phosphate (hexokinase/Glucokinase)
  • Fructose-6-Phosphate to Fructose-1,6-Bisphosphate (PFK-1) (KEY REGULATORY)
  • Phosphoenolpyruvate (PEP) to pyruvate (pyruvate kinase)
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6
Q

Describe regulation of Glucose to Glucose-6-Phosphate.

A
  • uses 1 ATP (traps glucose in cells)
  • hexokinase: INHIBITED by G6P
  • glucokinase: INDUCED by Insulin
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7
Q

Describe regulation of Fructose-6-Phosphate to Fructose-1,6-Bisphosphate (PFK-1).

A

-uses 1 ATP
-AMP and F-2,6-P activates
-ATP and citrate (plenty of stuff around to make ATP) inhibit
-Fructose 2,6-bisphosphate is the most potent activator of PFK-1
-formed by PFK-2 from F6P (kinase) and can be converted back into F6P (phosphatase)
-In liver, kinase domain is active if dephosphorylated and inactive if phosphorylated
-when active F-2,6-P is formed and this activates PFK-1
**also controls when glycolysis or gluconeogenesis is happening because F-2,6-P is an inhibitor of fructose 1,6-bisphosphatase (an enzyme of gluconeogenesis)

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8
Q

Describe Phosphoenolpyruvate (PEP) to pyruvate (pyruvate kinase) regulation.

A
  • makes 1 ATP (2 per glucose molecule in glycolysis)
  • phosphorylation (cAMP dependent) and alanine (made through amino transferase into pyruvate) inhibits
  • F-1,6-P activates (feedforward mechanism)
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9
Q

Describe the well-fed state and its impact on glycolysis.

A

↓glucagon
↑insulin causes an ↑ in fructose 2,6-bisphosphate
↑ rate of glycolysis

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10
Q

Describe impact of starvation on glycolysis.

A

↑glucagon
↓insulin causes a ↓ in fructose 2,6-bisphosphate
↓ rate of glycolysis and ↑ rate of gluconeogenesis

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11
Q

Describe cAMP regulation of glycolysis.

A
  • G-protein coupled receptor gets bound by a hormone or neurotransmitter
  • G-proteins interact with receptor and activate adenylyl cyclase (makes cAMP from ATP)
  • stops when the hormone is no longer bound to receptor
  • cAMP activates protein kinases (Protein Kinase A) which phosphorylates enzymes (can either activate or inhibit them)
  • protein phosphatases dephosphorylate the proteins and cAMP gets hydrolyzed (so changes in protein aren’t permanent)
  • Cholera toxin and Whooping cough affect these G proteins
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12
Q

Describe insulin in regards to glycolysis.

A
  • opposes the cAMP cascade
    has intrinsic kinase activity that activate protein phosphatases that activate the hydrolysis of cAMP
    -Insulin decreases blood glucose level by promoting the rapid uptake, storage and use of glucose
    -especially a factor in muscle, adipose tissue and the liver
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13
Q

Describe insulin and its impact in the liver during glycolysis.

A
  • Liver: insulin inactivates Phosphorylase (causes liver glycogen to split into glucose) so it prevents the breakdown of glycogen; causes enhanced uptake of glucose from the blood by liver cells (inc activity of glucokinase)
  • activates the enzymes that promote glycogen synthesis (glycogen synthase)
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14
Q

Describe insulin and its impact in muscles during glycolysis.

A

-Muscle: increases the rate of glucose transport into resting cells (GLUT 4), stored as glycogen

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15
Q

Describe insulin and its impact in adipose tissue during glycolysis.

A

-Adipose Tissue: Insulin promotes FA Synthesis in the liver (makes TG which enter lipoproteins and go to adipose tissue)

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16
Q

Describe insulin and its impact in the wellfed state.

A
  • levels of insulin are elevated because of increased blood glucose (released by β cells of the Islets of Langerhans in the pancreas)
17
Q

Describe anaerobic glycolysis.

A

Anaerobic Glycolysis

  • Pyruvate is a branch point that can convert to multiple metabolites
  • conversion to lactate by lactate dehydrogenase
  • formed in muscles when NADH production exceeds the oxidative capacity of the muscle (extreme exercise)
  • too much lactate can cause lactic acidosis: lowering of blood pH
  • occurs when inadequate oxygen and cells need to generate ATP (backup)
  • Only net production of 2 ATP (NAD/NADH made and used) compared to 2 ATP and 2NADH in aerobic glycolysis