Glycolysis Flashcards

1
Q

What is the major class of transmembrane proteins that are involved in sugar transport?

A

GLUT1-GLUT5

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2
Q

GLUT2

A

Allows for the transport of glucose into and out of cells. Found in he liver, kidney, and pancreas. Relatively high Km, which means that it will only pick up Glucose in times of plentiful glucose.

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3
Q

GLUT-4

A

It is insulin sensitive. Allows for the insulin regulated uptake of glucose in fat and muscle.

  • “you need insulin 4 the Glut 4 in your 4 limbs of muscle and fat”
  • more insulin will cause more Glut4 receptors to go to the cell surface and thus more glucose uptake.
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4
Q

What is the point of phosphorylating glucose?

A

Basically it maintains the downhill gradient for glucose to get into the cells because only the intracellular glucose is phosphorylated. So now, the concentration of straight glucose goes down in the cell. This is called Glucose-6-phosphate

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5
Q

WHat enzymes catalyze the reaction of Glucose –> Glucose-6-phosphate?

A

Hexokinase and Glucokinase

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6
Q

Difference between Hexokinase and Glucokinase?

A

Hexokinase - Low Km and low Vmax. It is relatively broad with regards to what it can catalyze - it will catalyze many 6-carbon sugars.
Glucokinase - located in the liver and pancreas it has a high Km and a high Vmax.

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7
Q

Feedback of Glucokinase

A
  • inhibited by Fructose-6-phosphate because F6P goes into the nucleus and binds to the Glucokinase Regulatory protein.
  • –This is reversed in times of high intracellular glucose content as well as high intracellular fructose-1-phosphate.
  • Glucokinase expression is stimulated by insulin.
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8
Q

What is the. First reaction in glycolysis??

A

Glucose to. Glucose-6-phosphate. ATP is. Used.

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9
Q

What happens after the creation of glucose-6-phosphate?

A

G6P is isomerized into Fructose-6-phosphate

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10
Q

What happens after F6P is made?

A

F6P gets phosphorylated by an enzyme called PFK-1 in order to make Fructose 1,6-bisphosphate.

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11
Q

PFK-1

A

Phosphorylates F6P into Fructose 1,6-bisphosphate. This is the rate limiting step in glycolysis and is irreversible.

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12
Q

Feedback of PFK1

A

Negative - ATP, CitraTe, and low pH
Positive - AMP and Fructose 2,6 - bisphosphate
- makes sense because when ATP is. Low you want ATP.

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13
Q

What enzymes affect fructose 2,6 - bisphosphate levels?

A

PFK2 - Catalyzes the reaction: Fructose-6-phosphate –> Fructose 2,6 - bisphosphate
FBP-2 - Catalyzes the reverse reaction of: Fructose 2,6 - bisphosphate –> Fructose-6-phosphate

These 2 enzymes are technically found together on the same protein.

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14
Q

How does PFK2/FBP2 get regulated? What regulates the thing. That regulates this?

A

Through phosphorylation events.

This is regulated through signal transduction cascades led by insulin/glucagon.

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15
Q

What is the first step of the energy generation phase?

A

Aldosterone A converting Fructose 1,6 - bisphosphate into glyceraldehyde 3-phosphate dihydroxyacetone phosphate.

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16
Q

What are the names of the two phases of glycolysis

A

Energy investment phase

Energy generation

17
Q

Glut-5

A

Primarily transports fructose as we saw in a different lecture.

18
Q

Glut-1

What happens if you have a deficiency?

A

Brain

- the brain doesn’t get enough glucose and therefore the patient has impaired neurological function.

19
Q

How is Glucokinase regulated??

A

By Fructose 6 phosphate - through a mechanism in the nucleus
- also by insulin (+) and glucagon (-)

20
Q

How does Fructose 2,6 bisphosphate get regulated?

A

Through PFK2.

  • Insulin activates PFK-2 through dephosphorylation
  • glucagon inactivates PFK-2 through phosphorylation.

— thin about it, PFK-1 makes Fructose 1,6 bisphosphate, PFK-2 makes Fructose-2,6 bisphosphate

21
Q

What is the difference bwteen liver PFK-2. And skeletal. Muscle PFK-2?

A

PFK-2 is regulated hormonally through insulin and glucagon in the liver
In skeletal muscle, PFK-2 is dependent on allosteric regulation by AMP.

22
Q

WHat regulation is there on pyruvate kinase?

A
\+ = Fructose 1,6 bisphosphate and insulin
- = glucagon
23
Q

How does pyruvate being shunted into lactate in a low low oxygen environment provide ATP?

A

Because it allows regeneration of NAD+ from NADH, which will allow glycolysis to repeat again for a 2 ATP gain each cycle.

24
Q

MODY

A

Mutations in Glucokinase

  • causes mild diabetes
  • monogenetic disorder
  • apparently the reason patients get diabetes is because Glucokinase also acts as a glucose receptor for pancreatic beta cells so the insulin receptors won’t be as responsive.
25
Q

Pyruvate kinase deficiency

A
  • hemolytic anemia
  • RBCs have insufficient ATP for their membrane pumps to they lyse.
  • – the cells are speculated and look like the ghosts from pac-man.
  • results in an increase in 2,3 BPG
26
Q

What does PDH do? (Protein dehydrogenase)

A

Converts pyruvate to acetyl CoA to start the TCA cycle.

27
Q

What are the 5 cofactors that affect PDH?

A
Thiamine - 1
Pantothenic acid -2 
Lipoic acid - 2
Riboflavin - 3
Niacin - 3
  • The Partly lying rabbinic nun
28
Q

Affect of arsenic and Mercury

A

Affects E2. Symptoms similar to beriberi.

29
Q

Tell tale sign of arsenic Poisening

A

Garlic scented breath

- also rice water stools and vomiting

30
Q

What provides negative feedback on PDH? How?

A

high energy molecules

  • acetyl CoA
  • ATP
  • NADH

They do this by activating PDH kinase, which phosphorylates PDH and thus activates it.
—therefore pyruvate will not be converted into Acetyl CoA

31
Q

What provides positive feedback on PDH?

A

insulin (and calcium)
- this makes sense because insulin indicates a fed state so there will be a lot of glucose and thus pyruvate so we want to convert all of that into energy.

— it does this by activating PDH phosphodiesterase, which de phosphorylates PDH and thus activates it

32
Q

Dichloroacetic acid

A

Pyruvate analog that binds to PDH kinase and therefore inhibits it. This means that PDH would remain in its de phosphorylated and active form.

33
Q

What would happen if you Have a pyruvate dehydrogenase complex deficiency?

A

You get accumulation of pyruvate and lactate.
- associated with delayed muscle development and reduced muscle tone often associated with ataxia And seizures. Could also have congenital malformations of the brain.

34
Q

How do we treat patients with a pyruvate dehydrogenase complex deficiency?

A

A ketone if diet and severe restriction of protein and carbs.
- this ensures that all the cells use acetyl-CoA from fat metabolism, so they don’t need PHD.

– if the mutation is in the E1 part then giving thiamine could help potentially.

35
Q

How much does one cycle of the TCA cycle make?

A

3 NADH
1 FADH2
GTP
2 CO2

  • in total this translates to 12 ATP
36
Q

Energy yield of Glycolysis + TCA

A

Glycolysis - 2 ATP and 2 NADH
TCA = 2 ATP + 6 NADH + 2 FADH2

= 32 ATP
Net. Energy production is 36 or 38 ATP for some reason

37
Q

What does fluoride do?

A

Inhibits enolase. The Km for bacteria is lower so it has a higher affinity for fluoride than humans do so it doesn’t harm us, just them