Lecture 6: Carbohydrate Metabolism Flashcards Preview

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Flashcards in Lecture 6: Carbohydrate Metabolism Deck (130):
1

What is the purpose of glycolysis?

MAKE ENERGY

2

What cells carry out glycolysis?

ALL cells

3

What is the raw material used for glycolysis?

Glucose is most common;

other sugars such as fructose and galactose can be used

4

In mammals:

_______ is the only fuel that red blood cells can use

Glucose

5

In mammals:


______ is the only fuel that brain uses under non-starvation conditions

Glucose

6

Initial step of glycolysis?

Transport of glucose into the cell;

Requires a transporter (glucose transporters {GLUTs} located in cell membrane

7

What are the transporters used for moving glucose into the cells?

Glucose transporters (GLUTs)

8

What are the 4 different types of GLUTs?

GLUT1
GLUT2
GLUT3
GLUT4

9

Where is GLUT1 found?

Ubiquitous but high in RBCs and brain

10

Where is GLUT2 found?

Liver and pancreas

11

Where is GLUT3 found?

Neurons

12

Where is GLUT4 found?

Skeletal muscle, adipose tissue

13

What is the only GLUT regulated by insulin?

GLUT4

14

Lowest Km for GLUT transporter?

GLUT2

15

Describe GLUT4:

GLUT4 is not always found in membrane. It is sequestered in vesicles in cells.

Insulin signaling causes fusion of vesicles with pm.

16

Describe the overview of Glycolysis:

1 molecule of glucose (6C) to 2 molecules of pyruvate (3C) and generates 2 ATP and 2 NADH

-Anaerobic process (no O2)

17

What occurs in glycolysis under aerobic conditions?

pyruvate can be completely oxidized generating much more ATP

18

Where in the cell does Glycolysis occur?

Cytoplasm

19

What are the three phases of glycolysis?

1. Investment
2. Splitting
3. Recoup/Payoff

20

What is the net yield of glycolysis?

2 ATP, 2 NADH, 2 Pyruvate

21

What is required in investment phase in glycolysis?

Requires 2 ATP

22

What occurs during the splitting phase of glycolysis?

One 6-carbon molecule into two 3-Carbon molecules

23

What occurs during the recoup/payoff phase of glycolysis?

4 ATP molecules generated

24

What are the three steps in PHASE 1 (INVESTMENT) phase of glycolysis?

1. Phosphorylation of Glucose to G6P
2. Isomerization of G6P to F6P
3. Phosphorylation of F6P to fructose 1,6-bisphosphate **rate limiting step

25

What is the rate limiting step in the investment phase of glycolysis?

3. Phosphorylation of F6P to fructose 1,6-bisphosphate

PFK

26

What enzyme is used in the investment phase of glycolysis that is rate limiting?

PFK

27

How many checkpoints/irreversible phosphorylation steps are there?

3

28

What are the 3 irreversible phosphorylation steps (use or generate ATP) catalyzed by?

-hexokinase/glucokinase
-phosphofructokinase-1
-pyruvate kinase

29

The activity of hexokinase/glucokinase, phosphofructokinase-1, pyruvate kinase are influenced by...

ATP, AMP, glucose, insulin and glucagon

30

What does Hexokinase/glucokinase do?

catalyzes the phosphorylation of glucose to G6P

*helps trap glucose inside cells

31

Where is hexokinase found?

present in all cells

32

Where is Glucokinase (GK) found?

Liver and pancreatic beta cells

33

What is the affinity of Hexokinase for glucose?

HIGH affinity!!!

34

What is the affinity of glucokinase for glucose?

LOW

35

What does PFK-1 do?

Catalyzes the conversion of F6P to F1,6BP

*rate limiting enxyme

36

What stimulates PFK-1?

Insulin

37

What inhibits PFK-1?

Glucagon

38

What does Pyruvate kinase (PK) do?

catalyzes the conversion of PEP into pyruvate and ATP

39

What activates PK?

F1, 6BP and insulin

40

What inhibits PK?

ATP, Alanine and glucagon

41

Regulation of Glycolysis during physical activity:

What occurs during rest?

Glycolysis inhibited

42

Regulation of Glycolysis during physical activity:

What occurs during exercise?

Glycolysis stimulated

***activated to meet energy requirements

43

Glycolytic intermediate:

Glucose 6 Phosphate....

What can it be used for?

-Precursor for PPP
-Converted to glucose 1-phosphate which is used in: (galactose metabolism, glycogen synthesis, uronic acid pathway)

44

Disorders of glycolysis:

What would be affected the most?

RBCs, Brain, HEMOLYTIC ANEMIAS

45

Disorders of glycolysis:

What enzyme is responsible for hemolytic anemias?

Pyruvate kinase

46

CORRELATION BOX: RBCs and Glycolysis

Why RBCs affected so severely when glycolysis is not working?

RBCs lack mitochondria, glycolysis is only mechanism for producing ATP

leads to hemolytic anemia

47

CORRELATION BOX: The Brain and Glucose

Why is the brain so susceptible to failure of glycolysis?

Glucose is one of the only fuel molecule that can pass the BLOOD BRAIN BARRIER (BBB)

48

CORRELATION BOX: The Brain and Glucose

How does the brain maintain energy during starvation?

Brain obtains glucose from the liver via gluconeogenesis;

can also utilize ketone bodies

49

CORRELATION BOX: Describe what occurs in in the body during the fed state.

Abundant glucose, increase uptake, increased rates of glycolysis, production of glycogen, decreased gluconeogenesis

50

CORRELATION BOX: Describe what occurs in in the body during the starvation state

low glucose; decrease uptake, more catabolism, less storage, increase in gluconeogenesis and glycogenolysis

51

CORRELATION BOX: What regulates the red state and fasting state?

relative amounts of insulin and glucagon in blood

52

CORRELATION BOX: Diabetes

What is type 1?

Loss of pancreatic beta cells, likely due to immune destruction

53

CORRELATION BOX: Diabetes

What is type 2?

Insulin resistance that progresses to loss of beta cell function

54

CORRELATION BOX: Hemolytic Anemia

Results from what?

Premature destruction of rbcs

55

What is TARUI disease?

Deficient in PFK-1

56

Whole body needs _____ g glucose per day

160 g

57

Daily glucose requirement of the brain?

120g

58

Glucose present in body fluids?

20g

59

Glucose readily available from glycogen is...

190g

60

Direct glucose reserves sufficient to meet glucose needs for ______

about one day

61

Gluconeogenesis is especially important ________

during a longer period of fasting or starvation

62

What is gluconeogenesis?

Synthesis of glucose from carbohydrate and non-carbohydrate precursors

63

When does gluconeogenesis occur?

When glucose and glycogen stores are depleted

64

Where in the body does gluconeogenesis occur?

liver, kidney and small intestine

65

What is the main conversion of gluconeogenesis?

Converts pyruvate into glucose

66

What are the major precursors of gluconeogenesis?

Lactate, amino acids and glycerol

67

What are the 3 major rate limiting enzymes used in the steps of glycolysis?

-Hexokinase/glucokinase
-Phosphofructokinase-1
-Pyruvate kinase

68

What are the 4 major rate limiting enzymes used in the steps of gluconeogenesis?

-Glucose 6-phosphatase
-Fructose 1,6-bisphosphatase
-PEP carboxykinase
-Pyruvate carboxylase

69

What are the positive regulators of Glycolysis?

Glucose, Insulin, AMP, Fru 2,6-BP, Fru 1,6-BP

70

What are the positive regulators of Gluconeogenesis?

Glucagon, citrate, cortisol, thyroxine, acetyl CoA

71

What are the negative regulators of Glycolysis?

Glucagon, ATP, citrate, Glc 6-P, Fru 6-P, alanine

72

What are the negative regulators of Gluconeogenesis?

ADP, AMP, Fru 2,6-BP

73

What is the rate limiting enzyme in glycolysis?

PFK-1

74

What hormones regulate PFK-1? Positively and negatively?

Positively: Insulin

Negatively: Glucagon

75

Regulation of PK: What activates?

F1,6BP and insulin

76

Regulation of PK: What inhibits?

ATP, Alanine and glucagon

77

What are the 4 potential fates of Glucose 6 Phosphate (G6P)?

1. Revert to glucose
2. Enter PPP to produce ribose and NADPH
3. Become pyruvate
4. Become glycogen

78

Most defects of glycolysis result in:

Hemolytic anemias

79

Gluconeogenesis:

Describe the generalities of this process

"By-passes" the 3 irreversible steps of glycolysis with assistance from 4 enzymes not present in glycolysis

80

Gluconeogenesis

What are the 4 enzymes present in gluconeogenesis that are not present in glycolysis

1. Pyruvate carboxylase
2. Phosphoenolpyruvate carboxykinase (PEPCK)
3. Fructose 1,6-bisphosphatase
4. Glucose 6-phosphatase

81

Gluconeogenesis

What is Pyruvate Carboxylase (PC)?

-Mitochondrial enzyme
-Catalyzes first step in gluconeogenesis
-Biotin cofactor

82

Gluconeogenesis

What enzyme catalyzes the first step?

Pyruvate Carboxylase (PC)

83

Gluconeogenesis

What is the rate limiting step?

Fructose 1,6-Bisphosphatase

84

What is the Cori Cycle?

Links the lactate produced from anaerobic glycolysis in RBC and exercising muscle to gluconeogenesis in liver

85

Name some examples of precursors of gluconeogenesis

Glycerol, Propionate, Alanine, Amino Acids

86

Gluconeogenesis

What are the three major categories of precursors?

-Carbohydrates
-Lipids
-Proteins

87

CORRELATION BOX:

What is F1,6BP deficiency?

-Similar to Tarui disease in glycolysis
-Hypoglycemia, lactic acidosis, ketosis, apnea, hyperventilation

88

Gluconeogenesis CORRELATION BOX:

What is Von Gierke disease caused by?

Deficiency in glucose 6 phosphatase

-inefficient release of free glucose into bloodstream by the liver in gluconeogenesis and glycogenolysis

89

When SUCROSE is cleaved, what are products?

Fructose + Glucose

90

When LACTOSE is cleaved, what are products?

Galactose + Glucose

91

Fructose is taken into cells by what?

GLUT5

92

Galactose/Glucose can be taken up into cells by?

SGLT1

93

CORRELATION BOX: What is Fanconi-Bickel syndrome?

-Autosomal recessive
-Mutation in GLUT2 transporter
-Unable to take up glucose, fructose and galactose

94

CORRELATION BOX: A mutation in GLUT 2 transporter leads to what syndrome?

Fanconi-Bickel

95

What is the Polyol Pathway?

Conversion of Glucose into Fructose

96

Polyol pathway:

Describe the conversions

-Glucose is reduced to SORBITOL by ALDOSE REDUCTASE
-SORBITOL oxidized to FRUCTOSE by SORBITOL DEHYDROGENASE

97

High fructose corn syrup (HFCS) is more efficiently converted to fat because...

it bypasses the rate limiting step of PFK-1

98

CORRELATION BOX: GALACTOSEMIA

what are the two types?

1.Deficiency in glucose 1P uritidyltransferase (GALT)
2. Deficiency in galactokinase

99

Pentose Phosphate Pathway (PPP): Summarize!

-Produces NO ENERGY
-Produces the sugar for DNA and RNA formation
-Produces NADPH

100

Where does PPP occur?

Cytosol

101

What are the major reactions of PPP?

-Oxidation of G6P to Ribulose 5-P
-Reduction of NADP+ to NADPH

102

What is the rate limiting step of PPP?

***G6P Dehydrogenase

Converts Glucose 6-P into 6-phosphoglucono-delta-lactone

103

Modulation of PPP:

What are two instances that would increase demand?

-High demand for Ribose 5P
-High demand for NADPH

104

Describe the structure of glycogen

-Glucose liked together via alpha-1,4 glycosidic bonds
-Branch points formed via alpha-1,6 glycosidic bonds

105

What is the non-reducing end of glycogen?

Terminal glucose w/ free hydroxyl group at carbon 4

106

What is the reducing end of glycogen?

Has glucose monomer connected to a protein called GLYCOGENIN

107

Where is glycogen stored?

Liver and muscle as granules

108

What is the function of LIVER GLYCOGEN?

Regulates blood glucose levels

109

What is the function of MUSCLE GLYCOGEN?

Provides reservoir of fuel (glucose) for physical activity

110

What are the three key steps of Glycogenesis?

1. Trapping and Activation of glucose
2. Elongation of glycogen primer
3. Branching of glycogen chains

111

Describe the 1st portion of Glycogenesis (Trapping and Activation of Glucose)

-Glucose converted to Glucose 6-P via hexokinase/glucokinase
-Glucose 6-p converted to Glucose 1-P via phosphoglucomutase (PGM)
-Glucose 1-P converted to UDP-Glucose via UDP-glucose phosphorylase

112

Describe the 2nd portion of Glycogenesis (Elongation of a glycogen primer)

UDP-glucose introduced to GLYCOGEN SYNTHASE which adds glucoses to alpha 1,4 glycosidic chain

113

What is the RATE LIMITING STEP in Glycogenesis?

***Glycogen synthase

114

Describe the 3rd portion of Glycogenesis (Branching of glycogen chains)

-Alpha 1,6 branches induced via GLUCOSYL (4:6) TRANSFERASE

115

What are the two key steps in GLYCOGENOLYSIS?

1. Chain shortening
2. Branch transfer and release of glucose

116

What is the RATE LIMITING enzyme of GLYCOGENOLYSIS?

Glycogen Phosphorylase (GP)

117

Why is it so important to regulate glycogen metabolism?

1. Maintain blood sugar
2. Provide energy to muscle

118

What are the TWO KEY ENZYMES involved in GLYCOGEN METABOLISM?

1. Glycogen synthase
2. Glycogen phosphorylase

119

Glycogen metabolism:

What activates...
Glycogen synthase vs. Glycogen phosphorylase?

Glycogen synthase: Dephospho

Glycogen phosphorylase: Phospho

120

Glycogen metabolism:

What inactivates...
Glycogen synthase vs. Glycogen phosphorylase?

Glycogen synthase: phospho

Glycogen phosphorylase: dephospho

121

What are the 4 key proteins involved in regulation by insulin?

1. GLUT4
2. Protein kinase B (PKB)
3. Protein phosphatase 1(PP1)
4. Glycogen synthase kinase 3 (GSK3)

122

Type 2 Diabetes, aka

Insulin resistance

123

Blood glucose criteria:

Normal blood glucose fasting vs fed

Fasting: 70-100mg/dL
Fed: less than or equal to 140 mg/dL

124

Blood glucose criteria:

Prediabetic/at risk:

Fasting: 100-125 mg/dL
Fed: greater than 140 mg/dL

125

Blood glucose criteria:

Diabetes mellitus:

Fasting: greater than or equal to 126 mg/dL
Fed: greater than or equal to 199 mg/dL

126

Regulation by Glucagon:

Key enzymes and second messengers?

-G protein
-Adenylate cyclase (AC) and cAMP
-Protein kinase A (PKA)
-Protein phosphatase 1 (PP1)
-Phosphorylase kinase (PK)

127

Glycogen storage diseases (GSD):

What type of disorders?

Disorders that affect breakdown or synthesis of glycogen

128

GSD 0

Deficiency in what?

Glycogen synthase

129

GSD III/Cori Disease

Deficiency in what?

1,6-glucosidase (debranching enzyme)

130

GSD IV/Andersen Disease

Deficiency in what?

Glucosyl (4:6) transferase (branching enzyme)