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POM UNC > Glycolysis & Gluconeogenesis > Flashcards

Glycolysis & Gluconeogenesis Flashcards

1
Q

What is glycolysis?

A

The breakdown of glucose into pyruvate. Pyruvate is modified to become acetyl CoA. The citric acid cycle (TCA, krebs) is used to turn Acetyl CoA into GTP, NADH, FADH2. NADH FADH2 go through electron transport chain to generate ATP for the cell.

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2
Q

What is gluconeogenesis?

A

Gluconeogenesis is the production of glucose from pyruvate, glycerol, amino acids.

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3
Q

Why do we need gluconeogenesis if we can get glucose from our diet?

A

Glycolysis (breakdown of glucose for energy) happens very quickly, and the energy is basically used up or stored for later. But we need glucose itself to support some cells, like red blood cells and neurons. We can’t store that much glucose in our bodies. Glycogen (basically chains of glucose) helps, but isn’t enough to last more than a day. After a day, the body needs a way to produce glucose to keep the brain from decaying. This is where gluconeogenesis comes into play.

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4
Q

Draw the steps in glycolysis

A

glucose + ATP –> (hexokinase) –> glucose 6 phosphate + ADP –> (phosphoglucose isomerase) –> fructose 6 phosphate + ATP –> (phosphofructokinase 1) –> fructose 1,6 bisphosphate + ADP –> (aldolase) –> 2X Glyceraldehyde 3 phosphate + NAD+ + P–> (glyceraldehyde phosphate dehydrogenase) –> 1,3 bisphosphoglycerate + NADH + H+. next step add ADP–> (phosphoglycerate kinase) –> 3 phosphoglycerate + ATP –> (phosphoglycerate mutase) –> 2 phosphoglycerate –> (enolase) –> phosphoenolpyruvate + H2O. next step add ADP –> (pyruvate kinase) –> pyruvate

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5
Q

Draw the steps in gluconeogenesis

A

start with 2 pyruvates. pyruvate +ATP + HCO3- –> (pyruvate carboxylase) –> oxaloacetate + ADP. next step add GTP–> (phosphoenolpyruvate carboxykinase) –> phosphoenolpyruvate + GDP + CO2. –> (enolase) –> 2 phosphoglycerate –> (phosphoglycerate mutase) –> 3 phosphoglycerate. next step add ATP –> (phosphoglycerate kinase) –> 1,3 bisphosphoglycerate + ADP. next step add NADH and P –> (glyceraldehyde 3 phosphate kinase) –> Glyceraldehyde 3 phosphate + NAD+ –> (aldolase) –> fructose 1,6 bisphosphate –> (fructose 1,6 bisphosphatase) –> fructose 6 phosphate + P. –> (glucose phosphate isomerase) –> glucose 6 phosphate. –> (glucose 6 phosphatase) –> glucose + P

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6
Q

What is phosphofructokinase 2?

A

An enzyme that creates fructose 2,6 bisphosphate, a signalling molecule whose presence induces glycolysis. PFK2 is regulated by the presence of glucagon and insulin. When it is phosphorylated it is inactive, and unable to cause glycolysis. It is phosphorylated by glucagon.

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7
Q

What are the irreversible/regulatory steps in glycolysis?

A

phosphorylation of glucose by hexokinase, phosphorylation of fructose 6 phosphate by phosphofructokinase 1, transfer of phosphate from phosphoenolpyruvate to pyruvate by pyruvate kinase. These all have highly negative Gibbs free energy.

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8
Q

Where is insulin produced?

A

Pancreas, beta cells

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9
Q

Where is glucagon produced?

A

Pancreas, alpha cells

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10
Q

What is insulin used for?

A

insulin is used to induce glycolysis after a meal to digest glucose and produce energy

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11
Q

What is glucagon used for?

A

glucagon is used to induce gluconeogenesis during a period of starvation so RBCs and the brain can continue to function. And other cells that would normally take in glucose (but brain is most important, it takes 3 times the glucose of the rest of the body)

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12
Q

What is insulin’s mechanism for affecting glycolysis/gluconeogenesis?

A

When glucose levels are high, insulin is present. Insulin activates a phosphatase that removes phosphate from PFK2. PFK2’s kinase domain (remember PFK2 has two domains, one phosphatase and one kinase) is activated without this phosphate and begins to convert fructose 6 phosphate to fructose 2,6 bisphosphate. F26bP induces glycolysis.

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13
Q

What is glucagon’s mechanism for affecting glycolysis/gluconeogenesis?

A

When insulin levels are low, glucagon is present. Glucagon activates a kinase, which adds a phosphate to the kinase domain of PFK2. This inactivates PFK2’s kinase domain, and activates its phosphatase domain. PFK2 is unable to convert F6P to F26bP, and glycolysis is not induced.

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14
Q

What is fructose 2,6 bisphosphate?

A

signalling molecule used to induce glycolysis! It’s formed from fructose 6-phosphate through the enzyme PFK2. F26bP activates PFK1, which turns fructose 6 phosphate into fructose 1,6 bisphosphate

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15
Q

What is fructose 1,6 bisphosphate?

A

a key intermediate molecule in glycolysis. It is formed by the reaction of fructose 6 phosphate through phosphofructokinase1

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16
Q

What it the output of glycolysis?

A

pyruvate, which is turned into acetyl CoA, which is used in the krebs cycle to make stuff like GTP and NADH and FADH2 which goes to make ATP in the electron transport chain.

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17
Q

What is the overall reaction for glycolysis?

A

1 glucose 2P + 2ADP + 2NAD+ –> 2ATP + 2 pyruvate + 2H2O + 2NADH + 2H+

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18
Q

What is the output of gluconeogenesis?

A

1 glucose molecule

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19
Q

What is the overall reaction for gluconeogenesis?

A

2 pyruvate + 4ATP + 2 GTP + 2 NADH + 6H2O –> glucose + 4ADP + 2GDP + 2NAD+ + 2H+ + 6p

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20
Q

How do the activity levels of glycolysis, glycogenolysis, and gluconeogenesis change over a period of days with fasting after an initial meal?

A

glycolysis is high right after eating and quickly diminishes (maybe 4 hours). Glycogenolysis (release of glucose from glycogen stores) ramps up at about 4 hours and lasts for a day, dying off around 18 hours. Gluconeogenesis begins to build around 16 hours, peaks at about 1.5 days, and then dips down but stays active at a fairly constant rate for about 40 days

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21
Q

What is the TCA cycle?

A

Krebs cycle, citric acid cycle. This takes acetyl CoA and through a series of reactions produces GTP, NADH, and FADH2. NADH and FADH2 are used to produce ATP in the electron transport chain.

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22
Q

What is the electron transport chain?

A

An opportunity to oxidize NADH and FADH2 back to NAD+ and FAD+. These reactions create buckets of ATP.

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23
Q

What are some pathways used in the electron transport chain to replenish NAD+?

A

glycerol 3-phosphate and malate-aspartate shuttles

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24
Q

What is NAD+? Where is it used? Where is it replenished?

A

NAD+ is a cofactor whose main role is to help in the transfer of electrons between groups. NAD+ is reduced to NADH. In the electron transport chain, NADH is oxidized into NAD+, and the freed hydrogen ions transport through a channel to produce ATP.

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25
Q

What are some common carbohydrates broken down in glycolysis?

A

Amylose, Amylopectin, Lactose, Glucose, Sucrose (all glucose components are separated and put through glycolysis)

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26
Q

Where can pyruvate come from?

A

pyruvate can come from amino acids, lipids, and glucose

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27
Q

Draw carbohydrate absorption by the gut

A

alpha-amylase starts to break things down in the mouth (saliva), alpha-dextrins digest in the stomach. bicarbonate and alpha-amlyase break things down in the small intestine.

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28
Q

What glucose transporters are present in the body? Where are they located? What are their identifying characteristics?

A

GLUT 1 - in all cells, base glucose input rate to meet needs of normal cells.
GLUT 2 - liver, only GLUT with the ability to take in glucose and send glucose out. Higher Km because it doesn’t want to take any needed glucose away from the rest of the body. Only pulls in glucose when there’s a crazy high concentration.
GLUT 3 - brain and placenta
GLUT 4 - muscles. You can actually increase the number of GLUT 4 transporters in your muscles by exercising (doing intense aerobic exercise). This allows your body to produce more energy while running.

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29
Q

What happens to glucose in anaerobic conditions? (assume it’s being used to generate energy)

A

It’s turned into pyruvate, and then turned into lactate. Process to pyruvate generates 2 ATP. Process to lactate generates NAD+, replenishing what was lost in the first steps. Lactate dehydrogenase is the key enzyme taking you from pyruvate to lactate.

30
Q

What happens to glucose in aerobic conditions? (assume it’s being used to generate energy)

A

It’s turned into pyruvate, turned into acetyl CoA, produces NADH and FADH2, used in electron transport chain to replenish NAD+ and FAD+ and to produce buckets of ATP

31
Q

Metabolically, how are RBCs different from the rest of cells in the body?

A

Red blood cells don’t have mitochondria so they’re not able to do krebs or the electron transport chain. This means they’re stuck only generating energy from glycolysis, so they have pretty big glucose needs compared to cells that can produce energy otherwise. Some anemias are caused when your red blood cells lose the ability to perform glycolysis and then don’t have any way to get energy so they die quickly.

32
Q

What are the steps in glycolysis? What are the major phases?

A

Two major phases: get to glyceraldehyde 3 phosphate and then get to pyruvate.
steps:
glucose + ATP –> (hexokinase) –> G6P + ADP. –> (glucose phosphate isomerase) F6P. next step adds ATP –> (phosphofructokinase1) –> F13bP + ADP. –> (aldolase) –> GAP. + NAD+ + Pi –> (glyceraldehyde 3 phosphate dehydrogenase) –> 1,3 phosphoglycerate + NADH + H+. next step adds ADP –> (phosphoglycerate kinase) –> 3 phosphoglycerate + ATP. –> (phosphoglycerate mutase) –> 2 phosphoglycerate –> (enolase) –> phosphoenolpyruvate + H2O. next step adds ADP –> (pyruvate kinase) –> ATP + pyruvate

33
Q

What is hexokinase? What is glucokinase? What are the differences?

A

Hexokinase is the enzyme used to convert glucose to glucose 6-phosphate and trap glucose in the glycolysis process. Hexokinase is present in all normal cells. In liver cells, where the majority of glycolysis occurs for the entire body, glucokinase replaces hexokinase. They do the same thing, but glucokinase has a worse binding affinity with glucose. This is a way to make sure that glucose can reach all cells it needs to before excess is taken up by the liver.

34
Q

Why is the hexokinase-catalyzed reaction irreversible?

A

glucose 6-phosphate can’t leave the cell, so it’s kind of trapped in that way. Plus buckets of energy are released (negative gibbs free energy)

35
Q

What is glucose 6-phosphate good for?

A

can be used in glycolysis, glycogen pathway, pentose phosphate pathway

36
Q

What does phosphoglucose isomerase do?

A

phosphoglucose isomerase takes you from Glucose 6 Phosphate to Fructose 6 Phosphate

37
Q

How many pyruvates come from one glucose molecule?

A

2!

38
Q

What are the products from the aldolase-catalyzed reaction?

A

you go from fructose 1,6 bisphosphate to 2 molecules of glyceraldehyde 3 phosphate

39
Q

What is DHAP?

A

An equivalent of glyceraldehyde 3 phosphate, except it has a slightly different structure and has to be bunged up by an isomerase to get GAP.

40
Q

What is GAP?

A

glyceraldehyde 3 phosphate. Halfway step in glycolysis

41
Q

What reaction does enolase facilitate?

A

takes a water out of 2 phosphoglycerate and turns it into phosphoenolpyruvate

42
Q

What reaction does pyruvate kinase facilitate?

A

phosphoenolpyruvate to pyruvate. This is one of the regulated steps (irreversible) of glycolysis

43
Q

What reaction does phosphoglycerate kinase facilitate?

A

phosphoglycerate kinase takes you from 1,3 biphosphoglycerate to 3 phosphoglycerate

44
Q

How is NAD+ replenished in anaerobic conditions?

A

through the production of lactate from pyruvate (uses lactate dehydrogenase)

45
Q

What are some activated carriers? What do they do?

A

NAD+, FAD+, they facilitate transport of electrons between molecules. Have highly energetic reduced states (NADH, FADH2)

46
Q

How much energy does aerobic glycolysis produce compared to anaerobic glycolysis?

A

like 32 atp compared to 2 atp

47
Q

Where does anaerobic glycolysis occur?

A

in cells that are deprived of oxygen. so in muscle cells after an intense workout.

48
Q

How does starvation induce gluconeogenesis?

A

Low glucose levels, brain and blood cells need glucose (as do other body parts, but brain needs a ton), so the pancreas secretes glucagon. Glucagon phosphorylates PFK2 and stops glycolysis from occurring. It also induces the transcription of gluconeogenesis-friendly enzymes.

49
Q

Where does gluconeogenesis occur?

A

In the liver! That’s why the liver has GLUT 2 transporters, so it can push glucose in and out of the cell

50
Q

What are alternative functions of glycolysis?

A

Glycolysis’s main function is to provide energy for the cell, but it can also be used to provide necessary intermediates for synthesis of important biological molecules (fatty acids, serine, alanine, five carbon sugars)

51
Q

What organ uses the most glucose every day?

A

The brain! It uses a ton of glucose, 3X what the rest of the body uses.

52
Q

What does lactate dehydrogenase do?

A

Faciliates the reaction from pyruvate to lactate, which replenishes NAD+ in the cell.

53
Q

Why are glycolysis and gluconeogenesis reciprocally regulated?

A

Glycolysis usually means you have a ton of glucose and you’re getting rid of it. Gluconeogenesis means you don’t hardly have any glucose and you need it. It doesn’t make sense for them to be active at the same time.

54
Q

What are feedback mechanisms for glycolysis?

A

Promoters: lots of glucose (want to get rid of it), lots of AMP or ADP (need more energy), lots of F2,6bP (insulin)

Inhibitors: lots of ATP (don’t need more energy), citrate (already gone through citric acid cycle)

55
Q

What are feedback mechanisms for the reaction with hexokinase?

A

glucose-6 phosphate (the product of hexokinase’s reaction) inhibits hexokinase from making further g6p. negative feedback.

56
Q

What are the feedback mechanisms for the reaction involving phosphofructokinase?

A

AMP, F26bP positive feedback

ATP, citrate are negative feedback

57
Q

How is pyruvate kinase’s activity modulated?

A

pyruvate kinase is active when it’s dephosphorylated, and is inactive when it’s been phosphorylated. In high glucose environments pyruvate kinase is dephosphorylated by insulin-dependent phosphatase, and glycolysis is stimulated. In low glucose environments pyruvate kinase is phosphorylated (and inactivated) by glucagon-dependent PKA, so glycolysis is stopped. F1,6bP stimulates pyruvate kinase (allosteric promoter) and ATP inhibits pyruvate kinase (allosteric inhibitor), because you don’t want to produce more energy in an energy rich environment.

58
Q

What parts of gluconeogenesis occur in the mitochondria?

A

The transition from pyruvate to oxaloacetate, to malate, and then the transport of malate out of the mitochondria into the cytosol.

59
Q

Where, in gluconeogenesis, is g6p transformed into glucose?

A

In the liver cells, in the endoplasmic reticulum. (there’s a glucose 6-phosphatase that takes the phosphate off glucose, and then there are transport proteins for each of the outputs)

60
Q

How does alcohol consumption regulate the lactate –> pyruvate reaction?

A

alcohol decreases the function of lactate dehydrogenase from making pyruvate. So if you’re starved and drunk you won’t be able to produce glucose to feed the brain.

61
Q

What enzymes catalyze the reaction from pyruvate to oxaloacetate?

A

pyruvate carboxylase and then phosphoenolpyruvate carboxykinase takes oxaloacetate to PEP

62
Q

How many times is oxaloacetate made in gluconeogenesis?

A

twice! once as a intermediate state to get to malate (oxaloacetate must not be able to get out of the mitochondria but malate can), and then malate is converted back to oxaloacetate in the cytosol. Oxaloacetate becomes phosphoenolpyruvate and then the inverse of glycolysis can occur.

63
Q

How does protein kinase A play a role in glycolysis & gluconeogenesis?

A

Protein kinase A is what’s activated by glucagon to phosphorylate PFK2 and inhibit glycolysis. Phosphoprotein phosphatase is used by insulin to take a phosphate off PFK2 and activate glycolysis

64
Q

What is fructose 1,6 bisphosphatase?

A

In gluconeogenesis, this is used to overcome the irreversible reaction from f6p to f16bP. It takes you from f16bP to f6p

65
Q

What is glucose 6 phosphatase?

A

In gluconeogenesis this is used to overcome the irreversible reaction from glucose to glucose 6 phosphate. so it takes you backwards from g6p to g

66
Q

What are ways to regulate gluconeogenesis?

A

promoters: tons of ATP, glucagon, not much glucose

inhibitors, tons of glucose (insulin), low energy environment (AMP)

67
Q

what reaction does pyruvate carboxylase facilitate?

A

pyruvate to oxaloacetate

68
Q

how do you get from pyruvate to phosphoenolpyruvate?

A

you start in the mitochondria, as pyruvate. pyruvate carboxylase takes you to oxaloacetate. oxaloacetate converts to malate, malate gets through mitochondria, converts back to oxaloacetate. oxaloacetate uses phosphoenolpyruvate to go from oxaloacetate to PEP

69
Q

what reaction does phosphoenolpyruvate carboxykinase facilitate?

A

oxaloacetate to PEP

70
Q

Does gluconeogenesis produce or require energy?

A

requires 4ATP 2 GTP.

71
Q

What is hemolytic anemia?

A

When your RBCs lose the ability to use pyruvate kinase, they can’t produce energy and they die. When they die they can’t carry oxygen around the body and you become anemic.

POM UNC (21 decks)

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