Carbohydrate Metabolism Pt. 2 Flashcards Preview

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Flashcards in Carbohydrate Metabolism Pt. 2 Deck (146):
1

How many grams of glucose does our body need in one day?

160 grams

2

How many grams of glucose does our brain need in one day?

120

3

How much glucose is present in our body fluids?

20

4

How much glucose is readily present in our glycogen?

190

5

Can our glycogen reserves provide glucose for long periods of time?

No. Our glycogen reserves only can give us about 190 g of glucose. Our body as a whole needs about 160g. Thus, we glycogen only gives us enough for about a day.

6

When is gluconeogenesis useful?

During longer periods of fasting, gluconeogenesis is v important.

7

What is gluconeogenesis

gluconeogenesis is the creation of glucose from carbs and non-carb precursors

8

When does gluconeogenesis occur?

Gluconeogenesis will occur when our glucose and glycogen stores have been depleted. That is, when we are starving, on a low carb diet (ketogenic diet) or during exercise.

9

Where does gluconeogenesis occur?

1. liver* (main site)
2. small intestine
3. kidney

10

Overall summary of gluconeogenesis?

Converts pyruvate--> glucose

11

What are the major precursors of gluconeogenesis?

1. lactate
2. AA
3. glycerol

12

Gluconeogenesis must bypass the irreversible steps of glycolysis. What enzymes do this?

1. Pyruvate carboxylase
2. PEP carboxykinase
3. F16Bisphophotase
4. Glucose-6-phosphotase

13

When is gluconeogenesis favored?

Glucose and glycogen are low

14

Tissue location of gluconeogenesis

1. liver- mostly
2. SI
3. kidney

15

Where does gluconeogenesis occur?

Gluconeogenesis occurs in two areas:
1. Mitochondria
2. Cytosol

16

Positive regulators of gluconeogenesis

1. glucagon
2. citrate
3. acetyl co-A
4. thyroxine
5. cortisol

17

Negative regulators of gluconeogenesis

1. ADP-
2. AMP
3. Fructose-2,6-BP

18

What is the net yield of gluconeogenesis? 0

Uses: 4 ATP and 2 GTP
Makes: 6 ATP equilvalents

so 0 net yield

19

What is the net yield of gluconeogenesis? 0

Uses: 4 ATP and 2 GTP
Makes: 6 ATP equilvalents

so 0 net yield

20

Pyruvate carboxylase in the gluconeogenesis

In gluconeogenesis, pyruvate carboxylase is the ONLY gluconeogenesis enzyme found in the MT. Here, it will convert [pyruvate-->OAA] though carboxylation.

Pyruvate carboxylase has a BIOTIN COFACTOR and is activated by [acetyl-coA] and [cortisol]

21

What type of co-factor does pyruvate carboxylase have?

Biotin cofactor

22

What activates the biotin co-factor on pyruvate carboxylase?

1. acetyl co-A
2. cortisol

23

How can we prevent gluconeogenesis from occuring all of the time?

As we have mentioned, pyruvate carboxylase converts [pyruvate--> OAA] in the MT. OAA cannot pass the MT membrane to go outside into the cytosol.

SOOO. OAA must be converted into [malate] by [malate dehydrogenase]. Malate can readily cross the MT membrane into the cytosol. It is then [REOXIDIZED] into OAA.

24

Pyruvate carboxylase is an enzyme located in the ______, that converts ______ to ______

MT
Pyruvate
OAA

25

Can OAA readily pass the MT membrane--> cytosol?

No. It must be converted to malate via malate DH in the MT and re-converted to OAA once outside.
This ensures that specificity of gluconeogenesis.

26

PEP Carboxykinase in gluconeogenesis

[OAA]--> [PEP] through phosphorylation & decarboxylation. A GTP is used.

27

Activators of PEP carboxykinase

Glucagon,
Cortisol
Thyroxine

28

What two processes are occur when PEP carboxykinase [OAA--> PEP]?

1. Phosphorylation
2. De-carboxylation

29

Fructose-1,6-Bisphosphotase in gluconeogenesis

Fructose-1,6-bisphosphotase converts [F16P-->F6P].
IT IS THE RATE LIMITING STEP

30

F16BPase activators

Cortisol
Citrate

31

F16BPase inhibitors

AMP
F26BP

[those two are both activators for glycolysis]

32

What is the rate limiting step in gluconeogenesis?

F16BPase.

33

Glucose-6-Phosphotase in Gluconeogenesis

[G6P--> glucose] via [G6Pase] via a dephosphorylation.

34

What activates G6Pase?

CORTISOL

35

What substance is a activator for all regulatory enzymes in gluconeogenesis?

CORTISOL. It is a activator of the biotin cofactor on Pyruvate kinase.

36

Where is G6Pase found?

SI, liver, kidneys and pancreas

37

G6P--> glucose via _____________, which is located in ______________

G6Pase
lumen of the ER

38

G6Pase has what kind of transporter?

GLUT7 transporter

39

Transportation of G6P and Glucose

1. G6P is transported into the lumen of the ER using a G6P transporter.
2. Here, G6Pase will convert G6P to glucose
3. Glucose is then moved to the cytoplasm using GLUT7 transporter

40

What is the relevance of the Cori Cycle?

As we have previously said, anaerobic glycolysis occurs in 1. exercising muscle and 2. RBC. It converts pyruvate--> [lactate]. However, we do not want a buildup of lactate in these cells. So, the Cori Cycle prevents this by moving lactate out of these cells, into the blood, into the liver where the lactate can undergo gluconeogenesis. Glucose is made and then sent back to [exercising muscle] and [RBC].

41

What are the two disorders that can occur in gluconeogenesis?

1. F-1,6-BP deficiency
2. Von Gierke Dz

42

What are the order of things broken down for gluconeogenesis?

1. Glycogen
2. Fat
3. Proteins

43

What happens where there is a F-1,6-BP deficiency in gluconeogenesis?

A F-1,6-BP deficiency in gluconeogenesis is similar to Tarui disease in glycolysis.

We are unable to make glucose from our sources.

44

Von Gierke Disease

Von Gierke disease occurs when there is a problem with glucose-6-phosphotase (G6Pase).

In this disease, glucose is essentially stuck inside of the cell and cannot be transported into the blood from the liver in [gluconeogenesis and glycogenolysis].

45

What cycles can Von Gierke Dz appear in?

1. Gluconeogenesis
2. Glycogenolysis

46

_________ can be cleaved by sucrase to make
__________ & _________.

Sucrose can be cleaved by sucrase to make
fructose & glucose

47

_________ can be cleaved by lactase to make
_________ & _______

Lactose can be cleaved by lactase to make
galactose & glucose

48

How does the cell take up fructose?

GLUT5 transporters

49

How does the cell take up [galactose] and [glucose], made from sucrose and lactose?

SGLT-1 Transporters

50

GLUT5 Transporters do what?

Move fructose into the cell

51

SGLT-1 Transporters do what?

Move galactose and glucose into the cell.

52

GLUT2 Transporters do what?

GLUT2 transporters move cells from [fructose, galactose and glucose] from the [CELL--> BLOOD].

So these work once these items are already inside the cell.

53

Fanconi-Bickel Syndrome

Fanconi Bickel Syndrome occurs when the GLUT2 receptors are fucked up. Fructose, glucose and galactose inside of the cell cannot be taken out into the bloodstream.

54

What are the genetics of Fanconi Bickel Syndrome?

Autosomal recessive

55

What transporter is affected in Fanconi Bickel Syndrome?

GLUT2- which moves fructose, galactose and glucose out of the cell into the bloodstream.

56

Polyol Pathway (basic)

Polyol pathway is the conversion of [glucose] into [fructose]

57

Why would we want to convert glucose to fructose in the polyol pathway?

We want to do this because fructose metabolism is FASTER. We can bypass the rate limiting step.

58

Describe the polyol pathway

[Glucose--> sorbitol] via aldose reductase
[Sorbital--> fructose] via sorbital DH

59

Pt Matthew lacks sorbital DH. What can happen?

Sorbital DH converts sorbital--> fructose.
If a patient lacks sorbital DH, they will have a build up of sorbital, which can cause cataracts.

60

How is fructose metabolized?

Fructose can be metabolized two ways:

1. Hexokinase can phosphorylate [fructose--> F6P], where it can then enter glycolysis.
HOWEVER...

Metabolism is faster if it bypasses the rate-limiting step and is converted into [glyceraldehyde-3-phosphate G3P].

61

Is High Fructose Corn Syrup linked to obesity?

It is thought that HFCS is linked to diabetes because since it passes the rate limiting step of PFK-1, it is easier turned to fat. However, only 55% of HFCS is fructose. the rest is sucrose. so, it is though that an overall increase in calories and sugar is linked to obesity.

62

Galactose Metabolism

Galactose can be metabolized and enter glycolysis as G6P

63

Galactose can be metabolized and enter glycolysis as

G6P

64

Enzymes in Galactose metabolism

Galactokinase
GALT

65

Pathway for galactose metabolism

galactose--> galactose-1-phosphate via [galactokinase]

galactose-1-phosphate--> glucose-1-phosphate via [GALT]

It will then eventually be turned into G6P and can enter glycolysis

66

What happens if there is a defect in ______ and ______ enzymes for galactose metabolism?

galactokinase and GALT

Galactosemia-->a build up of galactitol

67

Galactosemia

Galactosemia is a build up of galactose because GALT or galactokinase are defective.

Can cause cataracts

68

PPP is a oxidative/reductive pathway?

Oxidative

69

In the PPP, what is the primary substrate we begin with?

It takes G6P to make ribose and NADPH.

70

Does the PPP make energy?

No, it does not make ATP or GTP.

71

Where does the PPP occur?

Cytosol, like glycolysis.

72

What happens to G6P in PPP?

G6P is oxidized to ribulose-5-phosphate and NAD+ is reduced to NADPH.

73

2 main steps in PPP

1. oxidative that is irreversible (catabolic)
2. non-oxidative that is reversible (anabolic)

thus, PPP is AMPHIBOLIC!!!!!

74

Oxidative steps of PPP makes

2 NADPH and 1 CO2

75

There are ___ oxidatative steps in PPP.

2

76

1st oxidative step of PPP

G6P is oxidized by [G6P DH]
& NADP+ is reduced to NADPH.

This is the rate limiting step!

77

What were to happen if someone were deficient in G6P DH?

They would not be able to make NADPH. This occurs in a high proportion of African-Americans, making them more susceptible to hemolytic anemia.

78

Why is NADPH important though?

NADPH is super important because it helps to make glutathione, a anti-oxidant that helps us to detoxify H2O2.

79

2nd oxidative step in PPP

Phosphoglucanate DH will create ribulose-5-phosphate through decarboxylation.

CO2 is released and NADPH is made.

80

Non-oxidative steps in PPP

The second part of the PPP is non-oxidative. It turns ribulose 5-phosphate--> ribose-5-phosphate, the precursor to many nucleotides.

ribose 5 phosphate can then made [G3P or [F6P] and enter glycolysis or gluconeogenesis.

81

Non-oxidative part of PPP turns ________ into _______.

ribulose 5 phosphate
ribose-5-phosphate

82

Product of non-oxidative PPP (_______) can then do what?

ribose-5-phosphate

is the precursor to nucleotides.

ribose-5-phosphate can then be converted into G3P or F6P and then enter glycolysis.

83

A cell is dividing rapidly. Which phase of the PPP will it favor?

The rapidly dividing cell will favor the oxidative phase because it needs to make DNA.

This can also be obtained by reversing the non-oxidative phase.

84

Cells that have a high demand for NADPH will favor what phase of the PPP? Why?

A cell that has a high demand for NADPH will favor the non-oxidative phase. Why?


The non-oxidative phase creates metabolites that can enter glycolysis (G3P) and (F6P) and glucneogenesis. If these products are made, they can enter GLUCONEOGENESIS and re-enter the PPP.

85

What enzyme catalyzes the rate limiting step in PPP?

Glucose-6-Phosphate DH (G6P DH)

86

Glycogen is a polymer of _____

glucose

87

Glucoses in glycogen are held together by _______

alpha-1,4-glycosidic bonds

88

Polymers at the branch points of glycogen are held together by

alpha-1,6-glycosidic bonds

89

________ is the polymer for the production of glycogen

Glycogenin

90

The first glucose will attach itself to ______. This is called the ______ end.

The first glucose will attach itself to glycogenin. This is called the reducing end (not free.

91

The free end of glycogen is called the _______.

non-reducing

92

How can we spot the non-reducing end in glycogen?

OH group at the carbon 4.

93

How can we spot the reducing end of glycogen?

Reducing end is attached to glycogenin.

94

Glycogen storage

Glycogen is stored in granules in two places: the liver and muscle.

The granules has all of the enzymes needed to metabolize glycogen.

95

Are the roles for glycogen in the muscle and glycogen in the liver the same?

NO!

96

What does glycogen in the liver do?

Glycogen in the liver helps to regulate our blood sugar.

97

What does glycogen in the muscles do?

Used as a reservoir for when we are working out!

98

What are the three key steps in glycogenosis

1. Trap and activate glucose
2. Elongate the chain
3. NOW WE GOTTA BRANCH

99

Trap and activate glucose

1. hexokinase/glucokinase will bring glucose into the cell and trap it! --> G6P

2. G6P--> G1P [via PGM phosphoglucomutase]

3. G1P will then be tagged with UDP to create [UDP-Glucose]

100

Elongate the chain!

UDP-Glucose is added to the primer (glycogenin) via glycogen synthase

Rate limiting step!

This will continue

101

BRANCH THAT SHIT

Glucosyl (4:6) transferase will break the elongating chain and attach it elsewhere using a alpha-1,6-linkage

102

What enzyme is responsible for elongating the chain?

Glycogen synthase

Adds UPD-Glucose to glycogenin

103

What enzyme is responsible for branching?

glucosyl (4:6) transferase

breaks elongating chain and adds it somewhere else

104

What enzyme is the rate limiting step in glycogenosis?

Glycogen synthase

105

Glycogenolysis has ___ key steps

2

1. Chain shortening
2. Branch transfer to the long chain

106

Chain shortening in glycogenolysis

1. Glycogen phosphorylase will phosphorylate and remove glucose resides as [glucose-1-phosphates].
RATE LIMITING ENZYME
This will continue until you are 4 away from the branch point!

107

Branch Transfer to long chain in glycogenolysis

1. Debranching enzyme will remove 3/4 remaining glucoses and transfer them to chain and attach to the non-reducing end

We now have 1 glucose left. [Alpha-1,6-glucosidase] will now remove the last glucose and release it as a FREE glucose!

108

Glu-1-P and free glucose are released in a ratio of

10:1

109

What is the rate limiting step in glycogenolysis?

Glycogen phosphorylase

110

______ will remove the last glucose from the alpha-1,6-linkage and release it as a free glucose

alpha-1,6-glucosidase

111

What happens to Glu-1-P in the muscle?

Glu-1-P in the muscle is converted to G6P and enters glycolysis in the muscle to provide ATP.

G6P will never leave the cell because it does not have a G6Pase. Thus, as we said, the "glucose" in the muscle only fends for itself.

112

What happens to Glu-1-P in the liver?

converted to Glucose to help regulate our blood sugar.

113

Does glycogenolysis (glycogen breakdown) occur in the lysosome?

Yes.

114

alpha-1,6-glycosidase is also called

acid maltase

115

Pompe disease

Pompe disease occurs in lysosomal breakdown of glycogen when there is a problem with alpha-1,6-glycosidase. we have a hard time breaking down glycogen.

116

Why is regulation of glycogen metabolism important?

1. helps to maintain blood sugar
2. provides energy for our muscles.

117

For glycogen synthase to work, do you want it to be dephos or phosphorylated?

Glycogen synthase is active when it is DEphosphorylated

118

Glycogen phosphorylase is active when it is _______

phosphorylated.

119

For glycogen phosphorylase to be active, do you want it dephos or phosphorylated?

phosphorylated

120

Glycogenolysis is favored in the FASTING state. Why?

Blood glucose is low.
glucagon is high.

121

If Ca2+ and AMP is high in our muscles, what is this telling us?

glycogenolysis

122

[Q:] Does glucagon act on muscle?

NO. Muscle is not affected by insulin and glucagon because the glycogen in it is only used for the muscle.

123

Insulin binds to what kind of receptors?

tyrosine kinases

124

How does insulin regulate glycogen metabolism in terms of glycogen synthase and glycogen phosphorylase?

Insulin enters the body


Glycogen synthase will be dephosphorylated= making it active!

Glycogen phosphorylase will be dephosphorylated= inactive

125

How does glucagon regulate glycogen metabolism in terms of glycogen synthase and glycogen phosphorylase?

Glucagon is released in our body.

Glycogen synthase is phosphorylated= inactive

Glycogen phosphorylase is phosphorylated= active.

126

glucagon does/does not act on muscle

does not!!!

127

What protein kinase does glucagon activate?

Protein kinase A

128

Insulin and glycogen metabolism pathway

Increase insulin= increase glucose= glycogenosis

Glycogenosis occurs via glycogen synthase, which is active when DEPHOSPHORYLATED.

Insulin comes in and binds to tyrosine kinase. 2 things happen:
1. triggers glut4 receptors to membrane to let Glu in.

2. activates protein kinase B.

3. Protein kinase B will phosphorylate PP1 (protein phosphotase 1)

3. PP1 will dephosphorylate glycogen synthase and dephosphorylate glycogen phosphorylase.

YAY

129

insulin binds to

tyrosine kinase

130

glucagon binds to

GCPR

131

Epinephrine and glycogen metabolism

Epinephrine is released when we are working out in our muscles. it tells us to break down glycogen (glycogenolysis). Has the same mechanism as glucagon because it binds to the same receptors


Epi binds to GCPR
G protein will activate AC to convert ATP--> cAMP

cAMP activates protein kinase A

Protein kinase A will then phosphorylate glycogen synthase and glycogen phosphorylase.

YAY

132

All glycogen storing diseases are

autosomal recessive

133

Glycogen disorders that affect breakdown will do what?

cause

1. heptomegaly
2. hypoglycemia

134

Glycogen disorders that affect synthesis will

cause patient to depend on FREE glucose

135

GSDO

Enzyme affected:
Consequence:

Glycogen synthase

We cannot make glycogen because it is responsible for elongating the chain

136

Pompe disease

Enzyme affected:
Consequence:

Acid maltase (alpha-1,6- glucosidase)

Problem with lysosomal glycogenolysis.

We cannot release the last Glu to be released as a free glucose.

137

Cori Disease

Enzyme affected:
Consequence:

Debranching enzyme (alpha-1,6-glucosidase)

Consequence: long linear glucose with short branches

138

Von Gierkes Disease

Enzyme affected:
Consequence:

G6Pase
Affects glycogenolysis/gluconeogenesis

cannot release glucose

139

McArdles Disease

Enzyme affected:
Consequence:

Glycogenolysis

Glycogen phosphorylase in the muscle

We cannot provide NRG to our working muscle

140

Hers Disease

Enzyme affected:
Consequence:

Glycogenolysis

Glycogen phosphorylase in the liver

Cannot break glycogen down to provide glucose to regulate our blood sugar. thus, we will depend on only our free glucose

141

How can we treat glycogen storing disease?

Diet. A lot of them are inborn disease. Research is now pushing for enzyme replacement therapy

142

Liver glycogen phosphorylase and muscle glycogen phosohrylase are _______

isozymes

143

Mutation in liver glycogen phosphorylase leads to

Hers disease

144

Mutation in muscle glycogen P leads to

McArdles

145

What is the enzyme in glycogenesis that introduces the branch?

glucosyl 4:6 transferase

at 11 residues, will cut off and introduce at an alpha1:6linkage

146

Anderson disease

Enzyme affected:
Consequence:

Branching enzyme: glucosyl (4:6) transferase

Problem with glycogenesis

Long glycogen branches