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Pharm 411/412 > Glycolysis > Flashcards

Glycolysis Flashcards

1
Q

Which cells in the body can perform glycolysis?

A

Every Cell

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2
Q

When would a cell need to use immediate sources of ATP?

A

When energy levels are low

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3
Q

What is the first immediate cellular source of energy in muscle?

A 
Creatine Phosphate (CP)
Very high energy compound
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4
Q

How does Creatine phosphate help with ATP when the muscle needs energy?

A

It provides a reserve of phosphate energy to regenerate ATP, which is used during muscle contraction

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5
Q

What is the enzyme that catalyzes the reaction between creatine phosphate (CP) and ADP?

A

Creatine kinase to make Creatine and ATP

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6
Q

What is the second immediate energy source in muscle?

A

Myokinase (adenylate kinase)

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7
Q

What does myokinase do?

A

It has the ability to generate one ATP and one AMP from two ADPs

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8
Q

What is presence of AMP a signal of?

A

Its a profound signal for low energy state in our body

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9
Q

What organelle generates most of the cells supply of ATP?

A

The mitochondria

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10
Q

How many ATP does the TCA cycle generate?

A

24 ATP

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11
Q

How many ATP are generated from glycolysis?

A

8 ATP

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12
Q

What is the one fuel that can enter into the TCA?

A

A two carbon acetate, but it can not enter on its own so it needs a carrier, Coenzyme A or CoA
Once acetyl binds to CoA, it creates AcetylCoA and can enter the TCA

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13
Q

What must happen to glucose, fat and amino acids in order for the to be used in the TCA?

A

They must first be converted into acetyl-CoA before they can enter

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14
Q

Where does the acetyl (double carbon) come from to enter the TCA?

A

From glucose, fat, amino acids, ketone boy, and acetate AFTER it goes thro glycolysis
**remeber it must bind with Coenzyme A to form acetyl-CoA to enter TCA

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15
Q

What molecules does glycolysis make when it gets glucose?

A

In oxygen environment it makes pyruvate/pyruvic acid

When oxygen is absent it makes lactate/lactic acid

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16
Q

Where does the major energy extraction of glucose take place within our cells? (what gives us the most ATP)?

A

This happens during the TCA, BUT glycolysis but happen first

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17
Q

What happens to glucose when it enters glycolysis in the liver and muscle?

A

It goes thro glycogenosis which turns it into storage
Humans= glycogen
Plants= Amylose / amylopectin

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18
Q

What is a low energy state?

A

Glucose is alailable and high energy molecules (ATP, NADH and FADH) are low.
Molecules such as AMP and or ADP are high inside the cell

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19
Q

What happens to glucose when we are in a low energy state?

A

It will enter glycolysis and produce energy molecules

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20
Q

What is a high energy state?

A

This is when ATP is high and ADP is low inside the cell
***REMEMBER low energy state is not the same as starving state! this means that glucose levels do not need to be low in order to be in high energy state (Drinking beer which tricks liver)

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21
Q

What happens to glucose when we are in a high energy state?

A

It will not enter glycolysis but will be stored as glycogen in the muscle and liver

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22
Q

What is a starving state?

A

This is when glucose supply is low
The body will break down stored glycogen into glucose
Also there is a reversal of glycolysis known as gluconeogenesis to create more glucose

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23
Q

During a starving state why is it important that out body breaks down glycogen and perform gluconeogenesis?

A

The break down of the glycogen gives us glucose we can use
Gluconeogenesis gives us the ability to create more glucose to use
***Its important because we need to make sure to have enough glucose to use in our brain and RBC since they can not consume fat

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24
Q

Where does glycolysis take place?

A

in the cytosol (cytoplasm) and it happens in EVERY CELL!

This means most cells can metabolize glucose at least to pyruvate or lactate

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25
Q

Why is it important to note that cells like erythrocytes and cells in the lens and cornea of the eye do not contain mitochondria?

A

It means they cant utilize fatty acids as an energy source. They cant use the TCA or catabolize fatty acids so they rely on glycolysis for all of their ATP

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26
Q

Why cant brain cells metabolize fatty acids?

A

Even tho they have mitochondria, the dietary fatty acids they would be use can not cross the blood-brain barrier. They can store their own fatty acids but can not use fatty acids from diet or those secreted from adipose tissue or liver

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27
Q

Where is GLUT 1 located in the body?

A

High expression in endothelium of Blood-brain-barrier, RBC, fetal tissue. low expression in all cells
**Think glut 1 as blood

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28
Q

What are the features of GLUT 1?

A

Has a low Km (high affinity) This allows for preferential glucose uptake during hypoglycemia
Frequently upregulated in tumors
**has high affinity and found in blood, reason for this is because RBC must use lots of glucose to get ATP so it must be able to get it easily

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29
Q

What is the tissue distribution of GLUT 2?

A

Mainly in liver, kidney and pancreatic B-cell also some in intestine

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30
Q

What are the important features of GLUT 2?

A

It has a High Km (low affinity)
***This only becomes active when glucose levels are HIGH! and it will bring it into liver to be used as storage or be brought into pancreas to inc release of insulin

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31
Q

What is the tissue distribution of GLUT 3?

A

Neurons and placenta

**in the brain

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32
Q

What are the important features of GLUT 3?

A

Has the lowest Km (highest affinity)

this allows it to get preferential glucose uptake during hypoglycemia by the brain

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33
Q

What is the tissue distribution of GLUT 4?

A

Found in muscle and adipose tissue

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34
Q

What are the important features of GLUT 4?

A

has a medium Km
***INSULIN must be PRESENT in order for GLUT 4 to work
When someone takes insulin it causes GLUT 4 to become active and pulls the insulin into muscle and adipose tissue

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35
Q

Which GLUTs are found in nearly all mammalian cells?

A

GLUT 1 and GLUT 3, these are responsible for basal glucose uptake

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36
Q

Why is it important that the Km value for GLUT 1 and 3 for glucose is about 1-2 mM which is significantly less than the normal serum-glucose (4 - 8 mM)

A

This allows them bring glucose into the cell much easier than other cells and is the reason its over-expressed in cells/organs where glucose is essential

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37
Q

What is the energy investment Phase of glycolysis and which steps are they?

A

The energy investment stage means we use molecules of ATP and break down one glucose molecule (6 carbon) into two 3 carbon compounds
Steps 1-4

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38
Q

What is the energy payoff phase of glycolysis and which steps are they?

A 
Energy payoff means we get energy out of it
Two NADH (1 NADH = 3 ATP) molecules and 4 ATPs are produced 
Steps = 6-10
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39
Q

With 1 glucose what is the NET gain from glycolsis?

A

8 ATP
it produces 2 NADH and 4 ATP = 10 ATP
**remember in energy investment phase we use 2 ATP
10-2 = 8 ATP created

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40
Q

What is step one of Glycolysis?

A

It is irreversible but is NOT the committed step
It requires ATP and then HEXOKINASE (every cell) and GLUCOKINASE (liver) phosphorylate glucose and traps them inside the cell.
**Glucose-6-phosphate is created

41
Q

Why is the first step of glycolysis not the committed step?

A

Although it is irreversible it is not the committed step because there are metabolic options for the glucose
Glycolysis (energy production)
Pentose phosphate pathway (NADPH, nucleotide production)
Glycogen synthesis (storage)

42
Q

What are the differences between Glucokinase and Hexokinase?

A

Hexokinase present in every living cell - Glucokinase in liver and B-cell of pancreas
Km value of hexokinase is much lower than that of glucokinase
Hexokinase follows michaelis-menten and in glucokinase it DOES NOT

43
Q

How is hexokinase inhibited?

A

It has competitive inhibition with product inhibition by glucose-6-phosphate

44
Q

Does glucokinase get inhibited by its product?

A

No, when glucose levels are high GLUT 2 brings into liver and pancreas which is where glucokinase traps it
**Has insulin up-regulate synthesis, this means that if you have insulin it will cause more uptake of glucose which gets converted by glucokinase

45
Q

How do you covert mM to mg/dL?

A

You multiply or divide with 18

46
Q

What happens when you eat a a meal high in glucose?

take glucose orally

A

You secret GLP-1 (only works if glucose is available) this goes to pancreas which will cause it to release insulin

The glucose level is high in the blood it causes GLUT 2 in the pancreas to allow glucose in and release more insulin

GLUT 2 also becomes active in liver with causes it to bring in the glucose and create glycogen

With insulin in the blood it causes GLUT 4 to open in muscle and adipose to bring glucose into them

47
Q

What are the differences between taking glucose orally or when you get it thro IV? which will cause a higher spike in insulin and why?

A

When you take glucose orally it causes GLP-1 secretion which leads to an increase in insulin production

When glucose is given IV you will have less insulin production because GLP-1 is not secreted

48
Q

Is glycolysis inhibited in the liver?

A

No, the reason is because glucokinase is not inhibited by glucose-6-phosphate such as hexokinase so it will continue to process glucose

49
Q

What is the blood glucose level sensor of pancreatic B cells and liver?

A

Glucokinase in combination with GLUT 2

50
Q

What is the committed step of glycolysis?

A

Its the third step that requires ATP and is irreversible

51
Q

Why is step 3 the committed step of glycolysis?

A

Its because Fructose-6-phosphate get changed into Fructose-1,6-bisphosphate which is not used in any other pathway, meaning it must work in glycolysis

52
Q

What is the enzyme used in the third step of glycolysis?

A

Phosphofructokinase turns fructose-6-phosphate into fructose-1,6-bisphosphate

53
Q

How is phosphofructokinase regulated?

A

It is negatively regulated as a feed back mechanism by ATP (high energy step) and Citrate (downstream product accumulation, creating citrate downstream comes back and stops PFK-1)

54
Q

If you want to block glycolysis, would you block hexokinase of PFK-1?

A

You would block PFK-1 this is because once PFK-1 works to produce fructose-1,6 it will go thro glyolysis but if you stop hexokinase you would inhibit other pathways since it isn’t the committed step of glycolysis.

55
Q

What happens during step 4 of glycolysis?

A

Aldolase A cleaves fructose-1,6 biP into two pieces (goes from 6 carbon to 3 carbon) Only glyceraldehyde 3-phosphate is used. This means the other 3 carbon must be converted into glyceraldehyde to be used in glycolysis

56
Q

What is aldolase B?

A

It does the same thing aldolase A by converted fructose-1,6 biP into two 3 carbons but does it in the LIVER

57
Q

What is something important about aldolase B when it comes to fructose metabolism?

A

While it can cleave Fructose-1,6 bip it can also cleave fructose-1-P
**It has a low affinity for fructose-1-P compared to fructose-1,6 bip, this means if someone eats something high in fructose, fructose-1P tends to accumulate in the liver which causes dysfunction

58
Q

What happens during step 5 of glycolysis?

A

It creates two molecules of glyceraldhyde 3-phosphate that can go thro glycolysis
*uses triose phosphate isomerase

59
Q

What happens during step 6 of glycolysis?

A

The glyceraldehyde 3-phos gets oxidized by NAD+ and inorganic phos to from 1,3-bisphosphoglycerate and NADH (which can be extracted to 3 ATPs)

60
Q

What happens during arsenic poisoning?

A

Arsenic gets reduced to arsenite which is a substitute for inorganic phosphate. It binds to gyceraldehyde 3-phosphate dehydrogenase rxn and blocks glycolysis.
It also inhibits enzyme Pyruvate dehydrogenase
*has been used to block cancer

61
Q

What happens in step 7 of glycolysis?

A

1,3-bisphosphoglycerate which has a high energy phosphate which is transferred to an ADP to create ATP.
**this is substrate-level phosphorylation

62
Q

What is a substrate-level phosphorylation?

A

This happens when ATP is formed by phosphate group exchange between high energy molecule and ADP

63
Q

What happens during step 9 of glycolysis?

A

A second high energy compound, PEP, is formed by transferring the remaining phosphate in 3-phosphoglycerate

64
Q

What happens during step 10 of glycolysis?

A

Its the third and final irreversible step
Uses pyruvate kinase to produce pyruvate and ATP by substrate level phosphorylation
**all 6 carbons of glucose can be accounted for in the two molecules of pyruvates

65
Q

What inhibits step 10 of glycolysis, pyruvate kinase?

A

Its highly regulated and is inhibited by ATP (high energy state) and induced by F1-6 biP

66
Q

What is the most essential mineral for glycolysis?

A

Mg, if you dont have this in your diet or are deficient you can feel tired and fatigued due to not being able to produce ATP

67
Q

What do RBC do when they produce ATP?

A

They do anaerobic glycolysis to produce ATP which means they produce lactic acid which they release into the blood
**they dont have mitochondria which is why they do anaerobic

68
Q

What happens during anaerobic glycolysis?

A

The pyruvate is turned into lactate instead of entering the TCA cycle

69
Q

What is used during anaerobic glycloysis to convert the pyruvate?

A

It needs the two molecules of NADH that were produced during glycolysis

70
Q

Why is anaerobic glycloysis not sustainable?

A

Its because you need NADH to turn pyruvate into lactat. One problem is that oxygen is needed to turn NAD+ into NADH, so if you cant create NADH from the NAD+ you cant keep turning pyruvate into lactate
** also lactate since its an acid accumulates into the blood and causes acidosis (enzymes wont work)

71
Q

What is the total energy production in anaerobic glycolysis?

A

You get 2 ATP from one molecule of glucose

72
Q

When does the body perform anaerobic glycolysis?

A

it does so only under emergency conditions

73
Q

Why are athletes able to exercise longer?

A

They bypass anaerobic glycolysis by burning fat, increasing number of mitochondria and RBC

74
Q

Where do our bodies metabolize ethanol?

A

It happens in the liver and stomach

75
Q

What happens when someone takes ethanol?

A

its initiated mainly by NAD-dependent alcohol dehydrogenase (ADH)
Ethanol + NAD+ –> AD —> acetaldehyde + NADH —> acetaldehyde + NAD+ —>Aldehyde dehydrogenase —> acetic acid + NADH

76
Q

How many NADH can we produce from one ethanol?

A

We can produce 2 NADH

77
Q

Why is acetic acid important in break down of ethanol?

A

We can use acetic acid and it can combine with coenzyme A which will allow it to enter the TCA to produce more ATP

78
Q

Does alcohol produces more ATP than glucose?

A

Per gram it can produce more ATP than glucose

79
Q

What is the microsomal ethanol-oxidizing system?

A

Its the second pathway for oxidizing ethanol, it only functions at high concentrations of ethanol

80
Q

What does the MEOS oxidize ethanol to?

A

acetaldehyde

81
Q

What does MEOS use to oxidize the ethanol?

A

It uses NADPH, this is more wasteful way to metabolize compared to ADH. (to much drinking depletes NADPH which which is an antioxidant)
**Acetaldehyde to acetic acid is still catalyzed by acetaldehyde dehydrogenase

82
Q

What happens in the liver when you drink alcohol?

A

Since alcohol creates NADH which is a high energy molecule it gets tricked into thinking its in a high energy state. This leads it to not turn on glycogenolysis and glucoeogensis, which means it produces more fat.

**this is why it can lead to hypoglycemia (liver doesnt produce glucose by being tricked into thinking its high energy state so it thinks it needs to store it and not use it)

83
Q

What is the difference of fructose metabolism in the liver compared to glucose in terms of phosphofructokinase?

A

Fructose doesnt get regulated by phosphofructokinase (biggest rate limiting step) which leads to it producing more pyruvate which means it becomes acetyl CoA and then becomes fatty acid and cholesterol synthesis, this leads to obesity

84
Q

What are the intermediates and products of glycolysis that provide substrates for other pathways?

A

Glycerol
2,3-BPG
Pyruvate
Glucose-6-phosphate

85
Q

How is glycerol produced by glycolysis and whats it used for?

A

its used for storage of triglycerides and it used glycerol 3-phosphate dehydrogenase to create the glycerol

86
Q

What else does pyruvate create that is a substrate for another pathway?

A

It can get an amino group and produce the amino acid alanine

87
Q

What other role does glucose-6-phosphate have other then its step in glycolysis?

A

It is a precursor for the nucleotide sugar ribose 5-phosphate

88
Q

What leads to the production of 2,3 BPG

A

It uses 1,3 Biphosphoglycerate and creates 2,3 BPG

  • this gets up-regulated when oxygen level is low
  • *uses 2,3 BPG mutase which causes more 2,3BPG
89
Q

What are the three enzymes of the irrecersible steps of glycolysis?

A

Phosphofructokinase
Hexokinase
Pyruvate Kinase

90
Q

How is phosphofructokinase (PFK) regulated in glycolysis?

A

MAJOR regulatory enzyme
Blocked by ATP and Citrate (feed back inhibition)
**when energy state is high (high ATP/ADP) glycolysis is inhibited

91
Q

How is hexokinase inhibited in glycolysis?

A

It is directed feed back inhibition (product inhibition) by the products of the rxn it catalyzed glucose-6-phosphate

92
Q

How is pyruvate kinase inhibited in glycolysis?

A

It is inhibited by ATP

93
Q

What activates Pyruvate kinase?

A

It is activated by fructose-1,6-biphosphate

This is an example of feed forward activation

94
Q

What do high energy state block in glycolysis?

A

It blocks PFK and PK

95
Q

What is a pyruvate kinase deficiency?

A

The most common enzyme disorder of glycolysis.

It leads to impaired glycolysis which is particularly high impact on RBCs and can lead to hemolytic anemia

96
Q

What happens during mercury poisoning?

A

It affects glyceraldehyde 3-phosphate dehydrogenase which is essential for catalysis of 1,3-BPG (has high affinity for mercury) this stops glycolysis

97
Q

What is the warburg effect?

A

Found that most cancer cells predominantly produce energy by high rate of glycolysis followed by lactic acid fermentation in cytosol even if oxygen is present

98
Q

What do cancer cells consume more of than normal cells?

A

They use more glucose than normal cells to produce the same amount of ATP (use anerobic pathway so less ATP)
**GLUT 1 is usually over expressed (provides more glucose to use)

99
Q

What is 2D-Glucose?

A

Its an analog to glucose so it can bind with hexokinase but does not produce any metabolized products
**also stays longer which allows us to take pictures of it

Pharm 411/412 (11 decks)

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