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2) Biochemistry II > Glucose Metabolism > Flashcards

Glucose Metabolism Flashcards

1
Q

What are the main functions of glucose as a fuel?

A
  • Extracellular matrix and cell wall polysaccharides
  • Storage as glycogen, starch, and sucrose
  • Oxidized to Pyruvate via Glycolysis
  • Oxidized to Ribose-5-phosphate via the Pentose Phosphate Pathway
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2
Q

What is glycolysis?

A

Glucose is degraded to yield pyruvate, which yields some energy

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3
Q

What is gluconeogenesis?

A

Glucose is formed from a non-carbohydrate source; mainly proteins

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4
Q

What is glycogenesis?

A

Glycogen is polymerized from glucose units

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5
Q

What is glycogenolysis?

A

Glycogen is degraded to glucose units

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6
Q

What is glycolysis also called? Why?

A
  • EMP Pathway

- Because of the scientists: Euler-Meyerhof-Parnas

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7
Q

What was particular about the scientists Euler-Meyerhof-Parnas?

A

They were all Jewish scientists that practiced during the World Wars

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8
Q

In which mechanisms is DHAP located? (2) What can it become? Through what enzyme?

A

1) Glycolysis
- Triose phosphate isomerase
- Glyceraldehyde-3-phosphate
2) Fatty acid synthesis
- Glycerol-3-phosphate dehydrogenase
- Glycerol-3-phosphate

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9
Q

What does GAPDH stand for?

A

Glyceraldehyde-3-phosphate dehydrogenase

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10
Q

What does PEP stand for?

A

Phosphoenolpyruvate

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11
Q

Where does substrate-level phosphorylation occur in glycolysis?

A
  • Pyruvate kinase

- Phosphoglycerate kinase

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12
Q

Where does tautomerization occur in glycolysis? What is it?

A
  • Conversion of the double bond by exchanging electrons

- Pyruvate kinase

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13
Q

In glycolysis, why can phosphorylation only occur on C-6 in hexokinase?

A

Because C-1 is a carbonyl group and cannot be phosphorylated

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14
Q

What does phosphohexoisomerase do?

A
  • Converts Glucose-6-phosphate to Fructose-6-phosphate

- Moves the double bond to C-2 so that C-1 can be phosphorylated and become Fructose-1,6-bisphosphate

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15
Q

How many carbons do DHAP and glyceraldehyde-3-phosphate contain?

A

3 carbons each

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16
Q

What is used in glycolysis?

A
  • 1 Glucose
  • 2 ATP
  • 2 NAD+
  • 4 ADP
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17
Q

What is made in glycolysis?

A
  • 2 Pyruvate
  • 4 ATP (but 2 net)
  • 2 NADH
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18
Q

What must be done for glycolysis to continue?

A

NADH must be oxidized to NAD+ by fermentation

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19
Q

What can pyruvate generate under anaerobic conditions? (2)

A

1) Fermentation to 2 Ethanol and 2 CO2 in yeast

2) Fermentation to 2 Lactate

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20
Q

How is NAD+ generated in glycolysis?

A

By converting pyruvate to lactate through lactate dehydrogenase

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21
Q

What particular type of cells are capable of converting pyruvate to lactate? Why?

A
  • Erythrocytes since they do not have a mitochondria

- They need NAD+ to continue glycolysis

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22
Q

Where is lactate converted to glucose?

A

In the liver

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23
Q

What does the Cori Cycle explain?

A

How glucose is metabolized in muscles and how lactate is generated

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24
Q

What are possible glucose sources that can enter glycolysis?

A
  • Glucose
  • Lactose
  • Sucrose
  • They can enter at various points
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25
Q

What happens in glycogenolysis? What enzyme is required? What does it yield?

A
  • Glycogen phosphorylase
  • Glucose is made from glycogen
  • Glycogen is cleaved at its NON-reducing end
  • Yields glucose-1-phosphate
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26
Q

Which tissues depend mainly on glucose?

A

Brain, RBC, testes, renal medulla, embryo

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27
Q

What causes pregnancy-induced insulin resistance?

A

The embryo depends heavily on glucose

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28
Q

What compounds are converted to what in gluconeogenesis?

A
  • Formation of glucose from non-carbohydrate sources (pyruvate, glycerol, glucogenic AA)
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29
Q

What is the main site of gluconeogenesis? What are other sites?

A
  • Main: Liver

- Also, renal cortex and intestinal epithelium

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30
Q

Recovery after vigorous exercise involves ________________

A

gluconeogenesis

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31
Q

Which four enzymes are different in gluconeogenesis? Why?

A
  • To bypass non-reversible reactions in glycolysis
  • Pyruvate carboxylase and PEP carboxykinase
  • Fructose-1,6-biphosphoatase-1
  • Glucose-6-phosphatase
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32
Q

Which enzyme in glycolysis do pyruvate carboxylase and PEP carboxykinase replace in gluconeogenesis?

A

Pyruvate kinase

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33
Q

Which enzyme in glycolysis does fructose-1,6-biphosphoatase-1 replace in gluconeogenesis?

A

Phosphofructokinase-1

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34
Q

Which enzyme in glycolysis does glucose-6-phosphatase replace in gluconeogenesis?

A

Hexokinase

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35
Q

Which enzyme does pyruvate carboxylase resemble?

A

ACC since it contains biotin and uses ATP

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36
Q

What are the two steps to convert phosphoenolpyruvate from pyruvate?

A

1) Pyruvate + Bicarbonate –> Oxaloacetate

2) Oxaloacetate –> Phosphoenolpyruvate

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37
Q

What enzyme is used to convert: Pyruvate + Bicarbonate –> Oxaloacetate? Where does it occur? What energy source does it use?

A
  • Pyruvate carboxylase
  • Mitochondria
  • Uses ATP
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38
Q

What enzyme is used to convert: Oxaloacetate –> Phosphoenolpyruvate? Where does it occur? What energy source does it use?

A
  • PEP carboxykinase
  • Cytosol/Mitochondria
  • Uses GTP
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39
Q

All the intermediates of __________ can enter gluconeogenesis

A

Intermediates of TCA

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40
Q

Different AA yield different products in gluconeogenesis. What kind of products?

A

Pyruvate, a-ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate

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41
Q

Which AA are not glucogenic?

A

Leucine and Lysine

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42
Q

What are the two fates of Glucose-6-Phosphate?

A
  • Glycolysis

- Pentose Phosphate Pathway

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43
Q

What is the Pentose Phosphate Pathway also called?

A

Hexose monophosphate pathway

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44
Q

What is the Pentose Phosphate Pathway more common in?

A
  • Highly proliferative cells (ex: skin)
  • Cells of FA biosynthesis
  • Cells of sterol synthesis
  • Cells with oxidative stress (RBCs)
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45
Q

G6P leads to intermediates in two ways in the Pentose Phosphate Pathway. What are they?

A

1) Oxidative phase:
- G6P –> Ribulose-5-phosphate
2) Non-oxidative phase:
- Ribulose-5-phosphate –> G6P

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46
Q

What is the most important enzyme of the Pentose Phosphate Pathway?

A

G6P dehydrogenase

47
Q

What enzyme converts ribulose-5-phosphate to ribose-5-phosphate?

A

Phospho-pentose isomerase

48
Q

What can ribose-5-phosphate become? What is its use?

A
  • Nucleotides, coenzymes, DNA, RNA

- Proliferation and gene expression

49
Q

Where does NADPH come from?

A

From the Pentose Phosphate Pathway

50
Q

What are the functions of NADPH?

A
  • FA synthesis in liver, kidney, and lactating mammary gland
  • Cholesterol/steroid synthesis in liver, adrenal and gonads
  • Alleviation of oxidative stress
51
Q

What happens if hydrogen peroxide is not metabolized properly?

A
  • It yields a hydroxyl free radical

- Dangerous for lipids, proteins, and DNA

52
Q

How does NADPH alleviate oxidative stress?

A
  • NADPH is converted to NADP+ through glutathione reductase
  • Donates electrons and reduces GSSG to GSH
  • GSH has two hydrogens, which can be donated to hydrogen peroxide to turn them into water
53
Q

What is GSH? What is GSSG?

A

o GSH: reduced form of glutathione

o GSSG: oxidized form of glutathione

54
Q

What is the function of the Non-Oxidative Phase of the Pentose Phosphate Pathway? When is it used?

A
  • Regenerates G-6-P from R-5-P

* Used in tissues requiring more NADPH than R-5-P

55
Q

What regulates the Pentose Phosphate Pathway?

A

Intermediates, such as NADPH

56
Q

What does NADP+ do in terms of regulation of the pentose phosphate pathway? What does NADPH do in terms of regulation?

A
  • NADP+ activates G6PD and the PPP

- NADPH inhibits G6PD and the PPP (negative feedback - glycolysis will predominate)

57
Q

Why is glycolysis regulated?

A

To maintain constant ATP levels

58
Q

Which three enzymes are regulated in glycolysis?

A
  • Hexokinase
  • PFK-1
  • Pyruvate kinase
59
Q

Which compounds regulate expression/function of glycolytic enzymes?

A

Glucagon, epinephrine, and insulin

60
Q

How many isoforms does hexokinase have?

A

I to IV

61
Q

What are isozymes?

A

Slight differences in AA sequences, which creates slight changes in their function

62
Q

Hexokinase 4 is also called what?

A

Glucokinase

63
Q

Hexokinase I and II are predominantly expressed where? What do they have a high affinity for?

A
  • Muscle

- High affinity for glucose

64
Q

As the glucose concentration increases, how does the activity of Hexokinase I and II change? What about Hexokinase IV?

A

I and II: increases dramatically

IV: does not increase as much, lower affinity for glucose

65
Q

What are Hexokinase I and II allosterically inhibited by?

A

Glucose-6-phosphate, end-product of the reaction

66
Q

Where is Hexokinase IV predominantly expressed? How is their affinity for glucose?

A
  • Liver

- Low affinity for glucose

67
Q

Why is the low affinity for glucose of Hexokinase IV idea?

A

Since it is expressed in the liver, which does not used glucose (sends it to other body parts)

68
Q

Is Hexokinase IV inhibited by glucose-6-phosphate? What about Hexokinase I and II?

A

I and II: Yes

IV: No

69
Q

In the _____, glucose escapes glycolysis through a specific regulatory protein called _____

A

liver

GKRP

70
Q

How does glucose escape glycolysis in the liver at low concentrations?

A

GKRP binds to Hexokinase IV and translocates it into the nucleus, which is not a site of glycolysis

71
Q

When glucose concentration is low, ________ promotes the association between GKRP and hexokinase IV, which is shuttled to the nucleus

A

fructose-6-phosphate

72
Q

What are the three major sites of glycolysis and gluconeogenesis?

A

Liver, kidney, and epithelial cells

73
Q

When is hexokinase IV utilized to generate energy through glycolysis?

A

When there is high blood glucose

74
Q

In gluconeogenesis, what enzyme replaces hexokinase from glycolysis?

A

glucose-6-phosphatase

75
Q

In gluconeogenesis, what enzyme replaces PFK-1 from glycolysis?

A

fructose 1,6-bisphosphatase-1 (FBPase-1)

76
Q

In gluconeogenesis, what enzyme(s) replaces pyruvate kinase?

A
  • Pyruvate carboxylase

- PEP carboxykinase

77
Q

PFK-1 commits _____ to ______

A

glucose

glycolysis

78
Q

What inhibits PFK-1?

A
  • High ATP

- High citrate, which increases ATP-inhibition

79
Q

What stimulates PFK-1?

A
  • High ADP

- High AMP

80
Q

What inhibits FBPase-1?

A

High AMP

81
Q

What pathways does insulin promote?

A
  • Glycolysis
  • Glycogenesis
  • TG synthesis
82
Q

What pathway does glucagon inhibit? What does it stimulate?

A
  • Inhibits glycolysis

- Stimulates gluconeogenesis

83
Q

Is Fructose-2,6-bisphosphate used in glycolysis?

A

NO, it is just a regulator of the glycolytic pathway

84
Q

What does F26BP activate? What does it inhibit?

A
  • Activates PFK-1 (glycolysis)

- Inhibits FBPase-1 (gluconeogenesis)

85
Q

Fructose 2,6-bisphosphate is synthesized from ________ by _____, which requires ____

A

Fructose 6-phosphate
PFK-2
ATP

86
Q

Fructose 6-phosphate is synthesized from ___________ by __________, which does not require _____

A

Fructose 2,6-bisphophate
FBPase-2
ATP

87
Q

Are PFK-1 and FBPase-1 located on the same protein?

A

No

88
Q

Are PFK-2 and FBPase-2 located on the same protein?

A

Yes

89
Q

FBPase-2 is activated when PFK-2 is (phosphorylated/dephosphorylated)

A

phosphorylated

90
Q

What stimulates the phosphorylation of PFK-2?

A

Glucagon

91
Q

An increase of FBPase-2 stimulates what?

A

Gluconeogenesis

92
Q

Insulin causes (phosphorylation/dephosphorylation) of PFK-2 by stimulation what?

A

dephosphorylation

phosphoprotein phosphatase

93
Q

An increase of PFK-2 stimulates what?

A

Glycolysis

94
Q

Xylulose-5-phosphate is found where?

A

In the non-oxidative phase of the pentose phosphate pathway

95
Q

What is the role of xylulose-5-phosphate? What does it stimulate/inhibit?

A
  • Brings back glucose-6-phosphate to recycle glucose
  • Stimulates glycolysis
  • Inhibits gluconeogenesis
96
Q

High amounts of Xylulose-5-phosphate are acquired when there are high amounts of ______

A

glucose

97
Q

What inhibits pyruvate kinase?

A
  • Pyruvate
  • ATP
  • Acetyl-CoA
  • Long-chain fatty acids
98
Q

What activates pyruvate kinase?

A

Fructose 1,6-bisphosphate

99
Q

How is pyruvate kinase inactivated? Where does this occur?

A
  • When it is phosphorylated
  • ONLY occurs in the liver (muscle is not affected by PKA)
  • PKA phosphorylates it
100
Q

Pyruvate in the liver can undergo _________ to yield glucose, or _________ to yield energy

A

gluconeogenesis

TCA cycle

101
Q

How can pyruvate in the liver go through gluconeogenesis?

A

Converted to oxaloacetate by pyruvate carboxylase

102
Q

How can pyruvate in the liver go through the TCA cycle?

A

Converted to Acetyl-CoA by the pyruvate dehydrogenase complex

103
Q

What does high Acetyl-CoA concentration activate and inhibit?

A
  • Activates pyruvate carboxylase

- Inhibits the pyruvate dehydrogenase complex

104
Q

How does a high amount of glucose contribute to an increase in FA synthesis?

A
  • Glucose in PPP produces X-5-P
  • X-5-P activates a phosphatase, which dephosphorylates ChREBP, which moves to the nucleus
  • The dephosphorylation of ChREBP in the nucleus makes it mix with MLS
  • Once the mixture binds to ChoRE, they promote mRNA synthesis for a specific gene, such as Pyruvate kinase, Acetyl-CoA carboxylase, FA synthase
105
Q

How is FOXO1 inactivated? What happens?

A
  • Inactivated when it is phosphorylated

- Forces it to remain in the cytoplasm, degradation through ubiquination

106
Q

How is FOXO1 activated? What happens?

A
  • Activated when it is dephosphorylated by phosphoprotein phosphatase
  • Travels to the nucleus
107
Q

In the nucleus, FOXO1 creates mRNA sequences for what? They are enzymes of what?

A
  • PEP carboxykinase and glucose-6-phosphate

- Enzymes of gluconeogenesis

108
Q

FOXO1 suppresses the transcription of enzymes of which pathways?

A

Glycolysis, PPP, and FA synthesis

109
Q

What is the consequence of the fast multiplication of cancerous cells?

A

Oxygen cannot be provided quickly enough (hypoxia)

110
Q

In cancer cells, proteins are involved in which pathways?

A

Glycolysis and PPP

111
Q

What are the transcription factors called in cells exposed to hypoxia?

A

HIFI: Hypoxia-Inducible Factor 1

112
Q

What does HIFI activate? What does it inhibit?

A
  • Activates the enzymes of glycolysis

- Inhibits the enzymes that promote the synthesis of Acetyl-CoA

113
Q

Why does HIFI inhibit Acetyl-CoA synthesis?

A
  • Since the cells are exposed to hypoxia, they lack oxygen

- Acetyl-CoA is the precursor for the TCA cycle, which requires oxygen

114
Q

Why does HIFI promote the PPP?

A

Since precursors for DNA and RNA are from the PPP

2) Biochemistry II (23 decks)

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