Glycolysis Flashcards

1
Q

Give the affinity, tissues expressed and important note about GLUT 1

A

Tissue: All, RBC
Affinity: high [1mM ]
Important note: basal uptake of glucose

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2
Q

Give the affinity, tissues expressed and important note about GLUT 2

A

Tissue: Liver , pancreas, intestine
Affinity: low affinity [15-20mM]
Important Note: liver uptakes excess glucose, pancreas regulates insulin

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3
Q

Give the affinity, tissues expressed and important note about GLUT 3

A

Tissue: brain
Affinity: highest
Important note: high affinity basal uptake of glucose

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4
Q

Give the affinity, tissues expressed and important note about GLUT 4

A

Tissue: Muscles, heart and fat
Affinity : 5mM
Important note: regulated by insulin

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5
Q

What are the typical blood glucose levels

A

5mM

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6
Q

Explain the process of the glucose going from intestinal lumen to bloodstream (use as much detail as possible)

A
  1. High salt concentrations drive glucose into the epitheal cells via Na+ glucose symporter
  2. As this continues it builds high concentration of glucose inside the epithelial cells
  3. The high concentration of glucose with drive GLUT 2 uniporter to activate
  4. There is a downhill efflux of glucose out of the cell into the blood stream
  5. Na K+ ATPase will be drive 3 NA out of the out of the cell and 2 K+ inside of the cell making a concentration gradient
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7
Q

Describe the activity of GLUT 4 via the binding of insulin

A
  1. Insulin bind to its receptor which triggers a series a reactions
  2. One of the kinases will activate the GLUT 4 vesicle which moves it to the membrane of the cell AND activates phosphatase (PP-1)
  3. Phosphatase then dephosphorylates which increases the activity of glycogen synthase and decreases the activity of glycogen phosphorylase
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8
Q

What transporter in increased in endurance athletes?

A

GLUT 4

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9
Q

What does phosphatase do?

A

Dephosphorylates which increases the activity of glycogen synthase and decreases activity of glycogen phosphorylase

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10
Q

What enzyme opposes phosphatase?

A

Glucagon A kinase

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11
Q

What are some uses of glucose?

A
  • used in the cell wall
  • stored as glycogen
  • backbone of nuclei acids
  • used as pyruvate
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12
Q

How is NADPH produced?

A

Via reductive biosynthesis

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13
Q

What is the catabolic fate of pyruvate?

A

Pyruvate gets turned into ACoA via ox. Then to CO2 + water

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14
Q

What are the anabolic fates of pyruvate?

A

Lactate and ethanol

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15
Q

What is fermentation

A

Anaerobic breakdown of nutrient molecules without NET oxidation

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16
Q

What role Does phosphorylation play in the preparatory phase of glycolysis?

A
  • Keeps the glucose molecule inside the cell therefore it can’t go out via a transporter
  • it also destabilizes glucose
  • decrease glucose concentration so that more can go inside the cell
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17
Q

Describe the first step of glycolysis (use as much detail as possible)

A

Glucose + ATP <— hexokinase + Mg+ –> Glucose-6-phosphate + ADP + H+

-phosphate/ phosphoryl transfer
-coupled reaction
- product inhibition

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18
Q

What enzyme catalyze the first reaction in glycolysis

A

Hexokinase, the first ATP investment

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19
Q

What’s the difference between a phosphate and a phosphoryl transfer

A

Phosphate: OPO2-/3
Phosphoryl: PO2-/3

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20
Q

Why does ATP bond to the catalytic site unless glucose it there?

A

So it does catalyze the phosphoanhydride bond, water is now gone so it isn’t in the reactive

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21
Q

What are isozymes?

A

Different enzymes that catalyze the same reaction

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22
Q

What are the key features of hexokinase

A
  • Ubiquitous
  • less specific
  • high affinity therefore low km therefore hyperbolic shape
  • product inhibition
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23
Q

What transport is hexokinase most like

A

GLUT 1

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24
Q

What are the key features of glucokinase

A
  • liver and pancreas
  • low affinity therefor high km therefore sigmoidal
  • regulated by compartmentalization/ regulatory proteins
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25
Q

What transporter is glucokinase most like

A

GLUT 2

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26
Q

Describe the release of insulin in the pancreas

A
  1. Glucose enters the beta cells via the GLUT 2 channel
  2. Glucose is converted to pyruvate which produces CO2 and undergoes respiration in the mitochondria
  3. ATP is produced which inhibits the release of K+ via the ATP K+ channel t
  4. This causes depolarization which changes the voltage of the cell
  5. Change in voltage cause Ca2+ voltage gated channel to allow Ca+ into the cell which stimulates insulin to be released via exocytosis
27
Q

What regulates the pancreatic beta cells

A

Glucose

28
Q

Describe the regulation of glucokinase in the liver

A
  1. Glucose enters the hepatocyte via the GLUT 2 channel
  2. The increase in glucose (or increase in fructose-1-phosphate) activated glucokinase
  3. Conversion of glucose to glucose-6-phosphate follows
  4. Subsequent steps of glycolysis follow
29
Q

How is glucokinase inactivated?

A

Glucokinase binds to glucokinase regulatory protein which transport GK into the nucleus where it can’t catalyze reactions

Need increased glucose or fructose-1-phosphate to activate again

30
Q

What can happen to G-6-P in the heptocyte?

A
  1. Fills glycogen stores first
  2. Can be used for pyruvate which can be used in other reactions
31
Q

What does glucosephosphate isomerase do?

A

Converts glucose-6-phosphate into fructose-6-phosphate by opening up the 6 member ring, doing a isomerization then closing the ring

32
Q

What is the second step of glycolysis?

A

Glucose-6-phosphate gets converted to fructose-6-phosphate thru the enzyme phosphoglucose isomerase, reversible reaction

33
Q

What enzyme is used in 3rd step in glycolysis?

A

Fructose-6-phosphate + ATP gets converted into fructose-1,6-bisphosphate + ADP + H+ via phosphofructokinase-1

Phosphoryl transfer
Coupled reaction

34
Q

What does phosphofructokinase-1 do?

A

Catalyzes reaction fructose-6-phosphate to fructose-1,6-bisphosphate with Mg

35
Q

Which step is the committed step if glycolysis ?

A

Conversion of fructose-6-phosphate to fructose-1,6-bisphosphate

36
Q

Why is PFK-1 seen as the committed step?

A

Other steps are either reversible or glucose-6-phosphate can be used in other reaction such as making glycogen or pentose phosphate pathway

37
Q

How many ATP are yielded during the Energy investment stage of glycolysis

A

None, 2 are used

38
Q

What happens in the 4th step of glycolysis?

A

Fructose-1,6-bisphosphate is cleaved at carbon 3/4 via aldolase to produce Dihyroxyacetone phosphate (DHAP) and glyceraldehyde phosphate (GAP)

39
Q

What does Aldolase do?

A

It converts fructose-1,6-bisphosohate into DHAP and GAP

40
Q

What enzyme is used 5th step in glycolysis? Why type of reaction is this

A

Converting DHAP into GAP via triose phosphate isomerase
IRREVERSIBLE rxn

41
Q

What is the balanced energy equation for the energy investment stage of glycolysis?

A

Glucose + ATP —> 2 GAP + 2 ADP 2 H+

42
Q

What/ How is GAP converted into its product

A
  • GAP is converted in 1,3-bisphosphoglcerate through the enzyme glyceraldhyde-3-phosphate dehydrogenase (reversible)
  • ## Transfer of the Hydrogen on GAP to NAD+ to produce NADH and an inorganic phosphate transfer onto GAP
43
Q

What are the different energy rich intermediates in glycolysis

A

1,3-Bisphosphoglycerate and phosphoenolpyruvate

44
Q

Recall the energy recovery stage of glycolysis ( include all important enzymes/ reaction types etc)

A
  • Glyaldehyde-3-phosphate gets converted to 1,3 BPG via enzyme glycealdhyde3phosphate dehydrogenase
    NAD+ gets oxidized and phosphate gets added
  • 1,3 BPG gets converted into 3-phosphoglycerate + ATP via phosphoglycerate kinase doing a SLP
  • 3-phosphoglyceate gets converted into 2-phosphoglycerate via an phosphoglycerate mutase
  • 2-phosphoglycerate gets converted into PEP
  • PEP gets converted into pyruvate and ATP via pyruvate kinase
45
Q

What is the equation for glycolysis

A

1 glucose + 2 ADP + 2Pi —> 2 pyruvate + 4 ATP + 2 NADH + H + H2O

46
Q

How is 2,3-bisphosphoglycerate created and what is it’s significance?

A
  • 1,3 phosphoglycerate get converted into 2,3 Bisphosphoglycerate via phosphoglycerate kinase
  • 2,3 Bisphosphoglycerate stabilizes the T state in deoxyhemoglobin to make it easier to offload oxygen in the muscles
47
Q

Where can galactose enter into the glycolysis pathway?

A

Can enter where there is G6P, via galactokinase

48
Q

Where can fructose enter into the glycolysis pathway?

A

In the muscle: fructose-6-phosphate, hexokinase
In the liver: GAP, fructokinase

49
Q

How does fructose enter a hepatocyte?

A

Fructose is converted into fructose-1-phosphate via fructokinase due to a phosphate transfer

50
Q

What does fructose-1-phosphate indicate

A

Well feed state

51
Q

How is galactose converted to be used for glycolysis

A
  1. Galactose is converted to galactose-6-phosphate via galactokinase which under goes SLP
  2. Galactose-6-phosphate + UDP glucose create UDP-galactose and glucose-1-phosphate
  3. Glucose-1-phosphate is then isomerased to glucose 6 phosphate to glycolysis
  4. UDP-galactose is epimerased to for UDP-Glucose to release the cycle
52
Q

Provide an explaination as to how PFK-1 is an allosteric enzyme?

A

PFK-1 exists in 2 states, T state and R state. Also has 2 binding sites (substrate and allosteric)
T state is stabilized when ATP binds to allosteric site, making the enzyme inactive (Low affinity for ATP)
F6P preferentially binds to stabilize R state

53
Q

What are activators of PFK-1?

A

F6P + AMP + F2,6BP

54
Q

What inhibits PFK-1

A

ATP

55
Q

Why is AMP a more sensitive indicator than ADP

A

There’s lower amount of it in the cell therefore changes are more significant

56
Q

What does PFK-2

A

Convert Fructose6phosohate to fructose2,6bisphospate

57
Q

How is PFK-2 regulated in the liver?

A

Insulin increases activity and glucagon decrease’s activity

58
Q

How is PFK-2 regulated in the skeletal muscles?

A

Allosteric regulators

59
Q

Activators of pyruvate kinase

A

F1,6BP, feed forward activation

60
Q

What inhibits pyruvate kinase

A

Acetyl coa
Glucagon (only in liver)
ATP

61
Q

Explain the regulation of pyruvate kinase in the liver

A

Pyruvate kinase is in its inactive form when phosphorylated to be activated you need to dephosphorylate by
PP.
To then inactive you need to phosphorylate

62
Q

What activates AMPK

A

High levels of AMP

63
Q

What happens when AMPK is phosphorylated?

A

Switches from ATP consumption to ATP production