Chapter 8 - Glycolysis Flashcards

1
Q

How could you determine which molecule contains the most energy?

A

Whichever is the most reduced

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2
Q

Which 2 hormones regulate blood glucose concentration?

A

Insulin and glucagon

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3
Q

How does glucose get into cells?

A

It is carried by transporters

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4
Q

Glycolysis is the….

A

Oldest known and best studied pathway in living cells

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5
Q

What is the key purpose of glycolysis?

A

The net formation of ATP

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6
Q

Every intermediate in glycolysis serves as an….

A

Intermediate in another pathway in most cells

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7
Q

What are the 2 mobile cofactors in pyruvate production?

A

ATP and NADPH

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8
Q

Glycolysis pathway is a sequence of ____ enzymes that convert glucose to pyruvate

A

10

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9
Q

What is the most common end product in glycolysis? (According to the book)
What could be the other end product

A

According to book - lactate
Other = pyruvate

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10
Q

In the process of converting glucose to pyruvate, what high energy molecule is used?

A

NAD+

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11
Q

When there is not enough NAD+…..

A

Glucose can no longer become pyruvate

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12
Q

How does the body overcome the problem of a lack of NAD+?

A

Body has a way of converting NADH back to NAD+

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13
Q

All the enzymes that catalyze glycolysis exist in the….

A

Cytosol

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14
Q

Most mammalian cells use a ____ transport glucose protein called _____

A

Passive, GLUT

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15
Q

GLUT has ___ isoforms

A

14

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16
Q

What are isoforms?

A

Distinct proteins that have identical function but different kcat and km values

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17
Q

What is the function of the liver?

A

Convert glucose to glycogen

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18
Q

What is the function of the pancreas?

A

Secrets hormones that make the liver work - insulin, glucagon

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19
Q

The GLUT 1 transporter is found in____ and _____

A

Red blood cells and is prominent in fetal tissues

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20
Q

GLUT2 transporter is found in which 2 places?

A

Liver and pancreas

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21
Q

The km for GLUT2 is relatively….

A

High

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22
Q

The GLUT4 transporter is found in which 2 places?

A

Muscle and fat

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23
Q

Is the GLUT4 transporter insulin sensitive?

A

YES

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24
Q

GLUT1,2,4 - Which transporter uptakes glucose in response to extracellular glucose?

A

GLUT2

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25
Q

GLUT1,2,4 - Which transporter serves as the baseline glucose uptake for most cells?

A

GLUT1

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26
Q

The first step of glycolysis is catalyzed by…..

A

Hexokinase

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27
Q

What is the 1st step reaction (that hexokinase catalyzes)

A

Transfer of the phosphoryl group of ATP to glucose

Glucose + ATP —-> Glucose-6-P + ADP

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28
Q

What is the function of the hexokinase enzyme?

A

Protect the intermediates from hydrolysis. Conformational change among substrate (glucose) binding

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29
Q

Glucokinase is a _____ of hexokinase. It correlates with _____ transporter cells

A

Isozyme. Correlates with GLUT2 transporter cells

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30
Q

Most hexokinase enzymes have a similar affinity for….

A

Glucose

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31
Q

The km for glucokinase is very ….

A

High

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32
Q

Most hexokinase isozymes are product inhibited by….

A

Glucose-6-P

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33
Q

Which is the only transporter NOT inhibited by Glucose-6-P? WHY?

A

GLUT2 because it doesn’t have a transporter for removal

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34
Q

What is the 2nd step of glycolysis and what enzyme catalyzes it?

A

Isomerization of Glucose-6-P to Fructose-6-P.
Catalyzed by Glucose-6-P Isomerase

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35
Q

Explain what happens when Glucose-6-p is isomerized to fructose-6-P

A

Carbonyl moves from position 1 (aldehyde) to position 2 (ketone)

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36
Q

The isomerization of glucose-6-p to fructose-6-p is what kind of reaction?

A

An acid base reaction

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37
Q

Is the second step (isomerization) reversible?

A

YES

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38
Q

What is the 3rd step of glycolysis and what enzyme catalyzes it?

A

Phosphorylation of fructose-6-p to fructose-1,6-biphosphate
Catalyzed by PFK (Phosphofructokinase)

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39
Q

What is unique about the 3rd step of glycolysis?

A

It is the slowest step - the rate limiting step. PFK is the most regulated enzyme in the pathway

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40
Q

Is the 3rd step of glycolysis reversible?

A

(Phosphorylation of fructose-6-p)
NO

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41
Q

Which step of glycolysis has a nearly identical mechanism to the 1st step?

A

3rd step.

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42
Q

PFK is regulated ______ by a large number of enzymes

A

Allosterically

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43
Q

What are the 2 major regulators of PFK?

A

Citrate
Fructose-2,6-biphosphate

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44
Q

Describe the citrate regulator of PFK

A

Negative modulator.
Pasteur effect - glucose utilization decreases in the presence of oxygen

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45
Q

Describe the fructose-2,6-biphosphate regulator of PFK

A

Positive modulator. Formed from fructose-6-p and catalyzed by PFK2

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46
Q

What is the 4th step of glycolysis and what enzyme catalyzes it?

A

Fructose 1,6P2 is split into 2 3 carbon intermediates - Dihydrxyacetone-P + Glyceraldehyde-P
Catalyzed by ALDOLASE

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47
Q

What is the 5th step of glycolysis and what enzyme catalyzes it?

A

Near equilibrium interconversion between Glyceraldehyde-P and Dehydroxyacetone-P
Catalyzed by Triose Phosphate Isomerase

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48
Q

The 5th step of glycolysis is similar in mechanism to the

A

2nd step - isomerization of glucose-6-p to fructose-6-p

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49
Q

In the 5th step of glycolysis, ALL dehydroxyacetone-p is converted to…

A

Glyceraldehyde-p

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50
Q

What is the 6th step of glycolysis and what enzyme catalyzes it?

A

Only oxidation reaction in glycolysis. Glyceraldehyde-P is converted to 1,3-bis-P-glycerate while NAD+ is reduced to NADH
Catalyzed by glyceraldehyde phosphate dehydrogenase

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51
Q

Which step of glycolysis was the first enzyme mechanism ever solved?

A

6th step :
Glyceraldehyde-P –> 1,3-bis-phosphoglycerate

regulated by glyceraldehyde phosphate dehydrogenase

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52
Q

Which enzyme catalyzes the ONLY oxidation reaction in glycolysis?

A

glyceraldehyde phosphate dehydrogenase (6th step)

Glyceraldehyde phosphate + NAD+ + Pi —><— 1,3-bis-phosphoglycerate +NADH

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53
Q

In the 6th step of glycolysis, which species is oxidized and which species is reduced?

A

NAD+ –><–NADH = reduction
Glyceraldehyde-P–><–1,3-bis-phospho glycerate = oxidation (1,3-bis gains an oxygen and a phosphate)

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54
Q

Which step is involved in a hydride transfer and what is a hydride transfer?

A

step 6. Hydrogen is transferred along with a pair of electrons to NAD+

55
Q

Which step has an -SH group involved in the reaction and what could this do?

A

6th step. -SH can react with heavy metals and other electron deficient molecules, leading to enzyme inhibition

56
Q

What is the first step of glycolysis in which ATP is produced?

A

7th step.
1,3bis—><—3-P-Glycerate
Phosphoglycerate kinase

57
Q

What is the 8th reaction in glycolysis and what enzyme catalyzes it?

A

3-Phospho-Glycerate—><—- 2-phospho-glycerate
enzyme = phosphoglycerate mutase

58
Q

the 9th step of glycolysis is a _____ reaction

A

dehydration

59
Q

What is the 9th reaction of glycolysis and what enzyme catalyzes it?

A

2-Phospho-glycerate–><–PEP (P-enolpyruvate)
catalyzed by enolase

60
Q

What can inhibit enolase in the 9th step?

A

fluoride

61
Q

is fluoride a strong inhibitor of glycolysis? why or why not?

A

NO - it is a weak inhibitor of enolase because enolase inhibition is fairly weak and nonselective

62
Q

What are the 2 ATP forming reactions of glycolysis?

A

7th step and 10th step

1,3-bis-phosphoglycerate—-><—3-phosphoglycerate by phosphoglycerate kinase

PEP—–> pyruvate
pyruvate kinase

63
Q

pyruvate kinase is regulated both ______ and by ____ modification

A

allosterically and by covalent modification

64
Q

What is the KEY ALLOSTERIC REGULATOR of pyruvate kinase?

A

Fructose-1,6-biphosphate (product of PFK)

65
Q

When PFK is more active, it ______ which in turn activates _____. What is this called?

A

When PFK is more active it PRODUCES MORE PRODUCTS which in turn activates PYRIVATE KINASE. This is called FEED-FORWARD ACTIVATION

66
Q

What enzymes phosphorylates and inactivates pyruvate kinase?

A

protein kinase A

67
Q

What would cause an activation of protein kinase A?

A

hormonal regulation

68
Q

In what organ is pyruvate kinase a SUBSTRATE for phosphorylation?

A

the liver

69
Q

What enzyme catalyzes DEphosphorylation and returns pyruvate kinase back to its active form?

A

protein phosphatase

70
Q

When would we WANT protein kinase A to attach a phosphate to pyruvate kinase?

A

when we don’t want glycolysis to be that active anymore

71
Q

Summary: What are the 2 COVALENT regulators of pyruvate kinase?

A

phosphorylates/deactivates pyruvate kinase = protein kinase A

dephosphorylates/activates = protein phosphatase

72
Q

What is the key ALLOSTERIC regulator of pyruvate kinase?

A

fructose-1,6-biphosphate (product of PFK). It ACTIVATES pyruvate kinase by binding

73
Q

What is the overall reaction of glycolysis?

A

Glucose + 2ADP + 2Pi + 2NAD+ —> 2pyruvate + 2ATP + 2NADH

74
Q

Which 2 molecules represent the connected ends of the glycolysis pathway?

A

glucose and pyruvate

75
Q

The other molecules in the equation (besides glucose and pyruvate) are called…

A

mobile cofactors

76
Q

what are the 2 categories of mobile cofactors in the glycolysis pathway?

A

phosphorylation cofactors and redox cofactors

77
Q

What are the phosphorylation cofactors?

A

ATP, ADP, Pi

78
Q

What are the redox cofactors?

A

NAD+, NADH

79
Q

NADH—>NAD+
Oxidation or reduction?

A

NADH is oxidized to NAD+

80
Q

How are the phosphorylation cofactors regenerated?

A

by all reactions in the cell that utilize energy in the form of ATP

81
Q

What reaction MUST happen for glycolysis to continually operate?

A

NADH must be reoxidized to NAD+

82
Q

How can the oxidation of NADH to NAD+ be accomplished? (2 ways)

A

the conversion of pyruvate to ethanol OR by the formation of lactate

83
Q

The formation of lactate from pyruvate is catalyzed by the near equilibrium enzyme….

A

lactate dehydrogenase

84
Q

Do any reactions follow the formation of lactate?

A

no- formation of lactate is a dead end in glucose metabolism

85
Q

Write the reaction for the formation of lactate from pyruvate

A

pyruvate + NADH —><— lactate +NAD+
catalyzed by lactate dehydrogenase

86
Q

There are many different ____ forms of the enzyme lactate dehydrogenase

A

izozyme

87
Q

Several izozymes of lactate dehydrogenase form for different proteins in the ___,___,and____

A

liver,muscles, and heart

88
Q

What can different izozoymes of lactate dehydrogenase be used for in a clinical setting?

A

to detect selective damage to heart cells. when they rupture, they will release lactate dehydrogenase into the bloodstream which can be differentiated from the other izozyme forms by electrophoresis

89
Q

Some organisms, such as ____, can convert glucose to ____ instead of lactate

A

some organisms, such as YEAST can convert glucose to ETHANOL instead of lactate

90
Q

What is the process called when organisms - such as yeast - convert glucose into ethanol?

A

fermentation

91
Q

fermentation is a form of ____

A

glycolsysis

92
Q

Fermentation has ____ steps. What are they?

A

2 steps:
1: Pyruvate—> Acetaldehyde + CO2

2: Acetaldehyde + NADH <—-> Ethanol + NAD+

93
Q

Why does the process of fermentation generate NAD+?

A

For glyceraldehyde phosphate dehydrogenase to continue glycolysis

94
Q

One function of glycolysis is to…..

A

provide energy as ATP for other pathways

95
Q

What is the NET gain of ATP in glycolysis?

A

2

96
Q

Is the overall change in deltaGdegree in glycolysis positive or negative? What does this mean

A

negative - meaning that the process of glycolysis is thermodynamically allowed

97
Q

In red blood cells, what is the ONLY means of ATP production?

A

GLYCOLYSIS

98
Q

On the thermodynamic graph of glycolysis, what 3 enzymes account for the 3 downwards sloping areas? why???

A

hexokinase
PFK
pyruvate kinase
This is so because they’re metabolically irreversible

99
Q

What do the shallow slopes on the thermodynamic graph account for?

A

near equilibrium reactions

100
Q

At high altitudes, 2,3-bis-phospho-glycerate _______ the affinity of oxygen for hemoglobin

A

DECREASES

101
Q

The formation pf 2,3-bis-phospho-glycerate is an example of a….

A

shunt pathway

102
Q

How is 2,3-bis-phospho-glycerate formed?

A

mutase enzyme catalyzes the reaction of 1,3-bis-phosphog-glycerate (from the glycolysis pathway)

103
Q

What does a phosphatase enzyme do?

A

takes a phosphate off a molecule

104
Q

Since Arsenate is similar electronically to ____, it can substitute for in the reaction with the enzyme ________

A

phosphate, glyceraldehyde-phosphate dehydrogenase

105
Q

When arsenate substitutes for phosphate in the glyceraldehyde-phosphate dehydrogenase reaction, what molecule is formed?

A

1-arseno-3-phospho-glycerate

106
Q

After 1-arseno-3-phospho-glycerate is produced, what happens?

A

it is RAPIDLY and nonenzymatically hydrolyzed to 3-phosphoglycerate

107
Q

In the liver, fructose is transported across the membrane via_____, where it is converted to _____

A

GLUT2, fructose-1-phosphate

108
Q

What is the purpose of phosphofructokinase?

A

rate limiting step for glucose metabolism

109
Q

What does fructose-1-phosphate do?

A

BYPASSES Phosphofructokinase metabolism, leading to rapid and uncontrolled entry of fructose into pathway

110
Q

Besides fructose, what other molecules can enter glycolysis?

A

galactose (derived from lactose)
Glycogen (polymer)

111
Q

What are some alternative endpoints of glycolysis?

A

-ethanol formation (by yeast and other microorganisms)
-mammals - pyruvate to alanine
-nearly ALL CELLS have a pathway for the complete oxidation of pyruvate

112
Q

What are the substrates and products of aldolase?

A

substrate: Frustose-1,6-biphosphate

products: dihydroxyacetone-phosphate and glyceraldehyde-phosphate

113
Q

What is the product of pyruvate kinase?

A

pyruvate

114
Q

In the last step of glycolysis, what high energy molecule is used to generate ATP?

(ex of Substrate level phosphorylation)

A

PEP

115
Q

During the process of glycolysis (converting glucose into 2 lactate molecules), how many NADH molecules are produced?

A

NONE - ALL NADH is converted back to NAD+

116
Q

more oxidized = ____ energy

A

less

117
Q

most reduced = ____ energy

A

most

118
Q

Why is it crucial to convert pyruvate to lactate in anaerobic conditions?

A

allows glucose to be continually broken down to make ATP due to the recycling of NADH to NAD+

119
Q

How many molecular oxygen is consumed during glycolysis of one glucose molecule?

A

ZERO

120
Q

Why is arsenate considered a poison when glycolysis is concerned?

A

it generates a shunt to bypass ATP production

121
Q

How many ATP are generated in the presence of arsenic?

A

ZERO

122
Q

What is the function of 2,3-biphopshoglycerate

A

releases more o2 from hemoglobin

123
Q

1,3-bis-phosphoglycerate contains a lot of _____ and thus can be used for _______

A

energy, substrate level phosphorylation

124
Q

what does insulin do?

A

helps glucose ENTER cells so that is can be used for energy

125
Q

When blood insulin concentration is high, what does the GLUT4 transporter do?

A

provides an increased uptake of glucose

126
Q

the km for GLUT1,4 is relatively____

A

low

127
Q

the km for which glucose transporter is relatively high?

A

GLUT2

128
Q

Which of the GLUT transporters is near equilibrium?

A

GLUT2

129
Q

Does a high km or low km mean the reaction is near equilibrium?

A

high km

130
Q

Why is it crucial to convert pyruvate to lactate in anaerobic conditions?

A

it allows glucose to be continuously broken down to make ATP due to the recycling of NADH to NAD+

131
Q

Which 2 enzymes catalyze substrate level phosphorylation?

A

phosphoglycerokinase and pyruvate kinase

132
Q

What molecule is made from an intermediate molecule in glycolysis and controls how hemoglobin binds to oxygen?

A

2,3-bis-phosphoglycerate

133
Q

What molecule increases PFK activity?

A

fructose2,3 biphosphate

134
Q

How many electrons can NAD+ absorb and carry?

A

2