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Flashcards in Carbohydrate Metabolism Deck (107):
1

What is the only fuel that RBCs can use? This is also the only fuel that the brain uses under non-starvation conditions

Glucose

2

De novo synthesis

Gluconeogenesis in liver

3

Why can’t glucose cross the cell membrane?

It is polar, so there are specialized glucose transporters located in the cell membrane

4

GLUT1

High in RBCs and brain

High affinity

5

GLUT2

Liver

Low affinity

6

GLUT3

Neurons

High affinity

7

GLUT4

Skeletal muscle, heart, adipose tissue

Insulin dependent

8

What type of diffusion is the uptake of glucose an example of?

Facilitated diffusion, since transporters are used

9

Which glucose transporter has the lowest affinity (highest Km) for glucose?

GLUT2

10

Describe how GLUT4 is insulin dependent

GLUT4 is a protein made in ribosomes that is then sequestered in vesicles in cells

Insulin signaling causes fusion of these vesicles with the plasma membrane, which allows GLUT4 to take up glucose

11

Glycolysis includes a sequence of reactions that metabolizes ______ and generates _______

1 molecule of glucose (6C) to 2 molecules of pyruvate (3C)

2 ATP and 2 NADH

12

Under aerobic conditions, glycolysis can yield ____ ATP, which then go on to the TCA cycle in mitochondria

34-36

13

Where does glycolysis occur?

Cytoplasm

14

There are 3 phases of glycolysis: investment, splitting, and recoup/payoff. Describe briefly what occurs in each

Investment: requires 2 ATP

Splitting: one 6C molecule into two 3C molecules

Recoup/payoff: 4 ATP molecules generated (2 net)

15

What is the net yield of products in glycolysis?

2 ATP, 2 NADH, 2 pyruvate

16

The first phase of glycolysis, investment, can be broken down further into 3 steps:

1. Phosphorylation of glucose to G6P

2. Isomerization of G6P to F6P

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

17

In glycolysis, glucose must be trapped in the cell. Describe how/when this occurs

This occurs during the phase 1 of glycolysis, when glucose is phosphorylated to G6P

The enzymes involved are hexokinase, Glucokinase (pancreatic beta cells)

This is an important regulatory step

18

What/when does the rate limiting step occur in glycolysis?

The rate-limiting step occurs in the first phase of glycolysis, investment

It is when F6P is phosphorylated to fructose 1,6-biphosphate

19

The second phase of glycolysis, splitting, can be further broken down into:

4. Cleavage of F1, 6BP

5. Isomerization

20

What catalyzes the cleavage of F1, 6BP in the splitting phase of glycolysis?

Aldolase A

21

The third phase of glycolysis, recoup/payoff, can be further broken down:

6. Phosphorylation of G3P

7. Conversion of 1,3-BPG to 3-PG

8. Formation of pyruvate

22

What step of glycolysis is irreversible?

The formation of pyruvate, which converts ADP to ATP

23

What occurs when 1,3-BPG is converted to 3-PG in the recoup/payoff phase of glycolysis?

ADP is converted to ATP

24

What occurs when G3P is phosphorylated in the recoup/payoff stage of glycolysis?

NAD+ is reduced to NADH

25

What are the checkpoints that help regulate glycolysis? What enzymes are they catalyzed by? What influences these enzyme’s activity?

3 irreversible phosphorylation steps


Hexokinase/glucokinase, phosphofructokinase-1, pyruvate kinase

ATP (low ATP = glycolysis), AMP, glucose, INSULIN & GLUCAGON!!!!

26

Catalyze the phosphorylation of glucose to G6P (helps trap glucose inside cells)

Hexokinase/glucokinase

27

Has a high affinity for glucose and is functional even at low levels

Inhibited by G6P (product)

Hexokinase

28

Low affinity for glucose

Most active when glucose is high

At low F6P, it translocates to nucleus

Glucokinase

29

What is the rate limiting enzyme in glycolysis? What does it do? Does increased or decreased activity of it favor glycolysis?

Phosphofrutokinase-1 (PFK-1)

Catalyze the conversion of F6P to F1,6BP

Increased

30

Activates PFK-1

AMP
F2,6BP
High insulin/low glucagon

31

Inhibits PFK-1

ATP
Citrate (TCA cycle)
High glucagon/low insulin

32

Catalyzes the conversion of PEP into pyruvate and ATP

Pyruvate kinase

33

Activates pyruvate kinase

F1,6BP
Insulin (dephosphorylation)

34

Inhibits pyruvate kinase

ATP
Alanine
Glucagon (phosphorylation)

35

At rest, a negative feedback loop is created in glycolysis when:

G6P accumulates, so hexokinase stops wanting to make it

36

Also a precursor for the pentose phosphate pathway to produce ribose and NADPH

Glucose-6-phosphate

(Converted to G1P for galactose metabolism, glycogen synthesis, ironic acid pathway)

37

What is the fate of pyruvate in RBCs and muscle cells?

Reduced to lactate, which regenerates NAD+

38

What is the fate of pyruvate in the mitochondria?

It is oxidized in the TCA cycle to acetyl CoA and then CO2

39

Pyruvate can be converted to this amino acid

Alanine

40

Which cells are most impacted by disorders of glycolysis?

Those that lack mitochondria— RBCs (most defects cause hemolytic anemias)

Also brain cells

41

Mutations in this enzyme affect the protein’s folding and activity and lead to nonspherocytic hemolytic anemia and neurologic impairment

Phosphoglucose isomerase

42

Mutations in these enzymes cause hemolytic anemia

Aldolase A
Pyruvate kinase

43

Mutations in this enzyme cause intermediate enzyme deficiency and are associated with neonatal onset hemolytic anemia and neurologic dysfunction

Triose phosphate isomerase

44

Where does the brain obtain glucose from during starvation?

Note: glucose is one of the only fuel molecules that can cross the blood brain barrier (BBB)

From the liver via gluconeogenesis

Can also utilize ketone bodies

45

Summarize carbohydrate metabolism in the fed state

Increased rates of glycolysis, production of glycogen

Decrease gluconeogenesis

46

Summarize carbohydrate metabolism in the fasting state

Increase in gluconeogenesis and glycoogenolysis

47

Diabetes due to loss off pancreatic beta cells

Type 1

48

Diabetes due to insulin resistance that progresses to loss of beta cell function

Type 2

49

Inherited defects in RBC membranes

Spherocytosis

50

Nutritional deficiencies in these 3 can cause hemolytic anemia

Iron, folate, vitamin B12

51

What are 2 clinical marketers of hemolytic anemia?

Elevated lactate dehydrogenase, unconjugated bilirubin

52

In this disease, the patient is deficient in PFK-1 (rate limiting step) and experiences exercise-induced muscle cramps and weakness and high bilirubin and jaundice

Tarui disease (GSD VII)

53

How much glucose does the whole body need a day?

The brain?

160 g/day

120 g/day

54

How much glucose is present in body fluids? How much is readily available from glycogen?

20g

190g

55

Where and when does gluconeogenesis occur?

In the liver, kidney, and small intestine

Occurs when glucose and glycogen stores are depleted

56

What does gluconeogenesis do? What are the major precursors?

Converts pyruvate into glucose

Lactate, amino acids, and glycerol

57

Does gluconeogenesis directly yield ATP?

No, it makes glucose

58

List the positive regulators for gluconeogenesis

Glucagon, citrate, cortisol, thyroxine, acetyl CoA

59

List the positive regulators for glycolysis

Glucose, insulin, AMP, Fru2,6-BP, Fru1,6-BP

60

List the negative regulators for gluconeogenesis

ADP AMP, Fru2,6-BP

61

List the negative regulators for glycolysis

Glucagon, ATP, citrate, G6P, F6P, alanine

62

Gluconeogenesis bypasses the 3 irreversible steps of glycolysis by using 4 enzymes not present in glycolysis. These are:

Pyruvate carboxylase

Phophoenolpyruvate carboxykinase

Fructose 1,6-biphosphatase

Glucose 6-phosphatase

63

A mitochondrial enzyme that forms oxaloacetate from pyruvate in step 1 of gluconeogenesis

Has biotin as a cofactor

Pyruvate carboxylase (PC)

64

OAA is reduced to malate by ______. It is then transported to the cytoplasm and re-oxidized to OAA by _______

Step 2 of gluconeogenesis

Mitochondrial malate dehydrogenase

Cytosolic malate dehydrogenase

65

In step 3 of gluconeogenesis, OAA is ddecarboxylated and phosphorylated to PEP by

Phosphoenolpyruvate carboxykinase (PEPCK)

66

The 4th, and rate limiting, step of gluconeogenesis

Fructose 1,6-biphosphate

67

The 5th step of gluconeogenesis, where _____ dephosphorylates G6P to form glucose

Glucose-6-phosphatase (located in the lumen of the ER)

68

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

Glucose from liver is transported back to RBC and muscle to prevent lactate accumulation and regenerate glucose

Lactate —> pyruvate —> gluconeogenesis

Cori cycle

69

3 important precursors of gluconeogenesis

Galactose, fructose, lactate (monosaccharides)

70

Deficiency in glucose-6-phosphatase causes this disease


It is caused by a mutation in a catalytic site

This means no free glucose is formed and leads to symptoms like fasting hypoglycemia, lactic acidosis, hepatomegaly, hyperlipidemia, and retarded growth

Von Gierke disease

71

Takes up fructose

GLUT5

72

Takes up galactose and glucose

SGLT1

73

Caused by GLUT2 mutation

Unable to take up glucose, fructose, and galactose

Symptoms: failure to thrive, hepatomegaly

Rx: vitamin D and phosphate, uncooked corn starch

Fanconi-Bickel syndrome

74

Reduces glucose to sorbitol

Aldose reductase

75

Oxidizes sorbitol to fructose

Cells that lack this can have water influx and swelling —> retinopathy, cataracts, peripheral neuropathy

Sorbitol dehydrogenase

76

Why is fructose easier to convert to fat?

It bypasses the rate limiting step of glycolysis d/t absence of PFK1

77

Describe galactose metabolism

Glucose 1p uriddyltransferase (GALT) converts galactose to G1P to G6P where it can enter glycolysis

78

Results from a deficiency in glucose 1P uridyltransferase (GALT), which leads to an accumulation of galactitol —> cataracts in babies

Can also result from a deficiency in galactokinase

Galactosemia

79

Produces the sugar for DNA and RNA formation as well as NADPH, but does not produce energy

Pentose phosphate pathway (PPP)

80

Where does the PPP take place?

Oxidation of G6P to ribulose 5P and 2 NADH

Irreversible oxidative and reversible non-oxidative steps

Cytosol

81

Summarize the oxidative phase of PPP, which involves the oxidation of G6P

-produce 2 NADPH and 1 CO2

-G6P dehydrogenase: rate-limiting step —> NADP+ to NADPH

-NADPH regenerates glutathione, an antioxidant

82

G6PD deficiency presents as hemolytic anemia and affects those from _____ descent

African

83

If thee cells have a high demand for ribose 5P (synthesize DNA), what phase of PPP is favored?

Oxidative phase to produce ribulose 5P

84

What occurs in PPP if there is a high cellular demand for NADPH?

Non-oxidative products are channeled into gluconeogenesis

85

There is very high PPP activity in what type of cells?

Phagocytic— infection!

86

Homopolymer of glucose

Glycogen

87

What type of bond links together the glucose molecule within a chain of glycogen?

A-1,4 glycosidic bonds

88

What bonds form the branch points in glycogen?

A-1,6 glycosidic bonds

89

Contain a terminal glucose with a free hydroxyl group at carbon 4

Non-reducing end of glycogen

90

Glucose monomer connected to a protein called glycogenin

Reducing end of glycogen

91

From which end is glycogen degraded and extended?

Non-reducing

92

How glycogen is stored in the liver and muscle; contain also enzymes needed for glycogen metabolism

Granules

93

Regulates blood glucose

Liver glycogen

94

Reservoir of fuel (glucose) for physical activity

Muscle glycogen

95

There are 3 key steps in glycogenesis:

1. Trapping/activation of glucose (glucokinase/hexokinase phosphorylated glucose to G6P —-> phosphoglucomutase to G1P)

2. Elongation of a glycogen primer

3. Branching of glycogen chanins

96

What is the rate limiting enzyme in glycogenesis?

Glycogen synthase

97

What is the rate limiting enzyme in glycogenolysis?

Glycogen phosphorylase (B6 is a cofactor)

98

Glycogen synthase is active in the _____ form.

Glycogen phosphorylase is active in the ______ form

Dephosphorylated

Phosphorylated

99

Does glucagon act on muscle?

No

100

Disorders that affect glycogen breakdown lead to:

Hepatomegaly and hypoglycemia

101

Disorders that affect glycogen synthesis lead to:

Patients dependent on glucose

102

Defective enzyme: glycogen synthase

Pathway affect: glycogenesis— chain elongation

GSD 0

103

Defective enzyme:
Acid maltase

Pathway affected: lysosomal glycogenolysis— release of glucose

GSD II / Pompe disease

104

Defective enzyme: glucosyl (4:6) transferase

Pathway affected: glycogenesis— chain branching

Long chain glycogen

Enlargement of liver and spleen, cirrhosis, death by 5

GSD IV / Andersen disease

105

Defective enzyme: muscle glycogen phosphorylase

Pathway affected: glycogenolysis— G1P release

Unable to supply muscles with enough glucose

Weakness, muscle cramps

Myoglobin in urine

GSD V / McArdle disease

106

Defective enzyme: liver glycogen phosphorylase

Pathway affected: glycogenolysis— G1P release

Prevents glycogen breakdown in liver —> hepatomegaly

Low blood glucose levels

GSD VI / Hers disease

107

Deficiency in a-1,6-gluosidase (debranching enzyme)

Lot of small branches

Light hypoglycemia and hepatomegaly

GSD III/Cori Disease