Glycolysis Flashcards

1
Q

Glycolysis occurs in

A

cytosol

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2
Q

Decreased function of glucokinase is assciated with

A

Maturity onset diabetes of the young

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3
Q

Fructose-6-phosphate can be converted into Fructose-2,6-bisphosphate by the enzyme

A

Phosphofructokinase 2

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4
Q

Fructose 2,6 bisphosphate induces glycolysis by upregulating the enzyme

A

PFK1

which converts fructose-6-phosphate to fructose 1,6 phosphate

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5
Q

PFK1 is inhibited by

A

Citrate
ATP

(Metabolites from ETC and Krebs)

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6
Q

In the well fed state, insulin is high which increases fructose 2, 6 phosphate utilized by both muscle and liver leading to increased hepatic

A

Glycolysis

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7
Q

On a fasting state, glucagon levels are high which decreases fructose 2,6 bisphosphate and will halt hepatic glycolysis and increase

A

Gluconeogenesis

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8
Q

Fructose 1,6 bisphosphatase converts fructose 1,6 phosphate to fructose 6 phosphate which allows liver to produce glucose and is inhibited by decreased

If fructose 2,6 bisphosphates is decreased, skeletal muscles are starved glucagon levels are high, hepatic gluconeogenesis is

A

fructose 2,6 bisphosphate

increased

allows liver to break down AA and other products to create glucose

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9
Q

A drug decreases hepatic concentration of fructose 2,6 bisphosphate.

How will this drug likely alter the activity of aspartate transaminase (converts asparate -> oxaloacetate)

A

Decreased fructose 2,6 bisphosphate results in gluconeogenesis

If gluconeogenesis is increased, there is increased catabolism of amino acid and glycerol

Asparate transaminase breaks down aspartate to oxaloacetate which increases during gluconeogenesis to make glucose

Increased activity of aspartate transaminase

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10
Q

Decrease in fructose 2,6 bisphosphate upregulated production of fructose 1,6 bisphosphatase resulting in increased production of fructose 6 phosphate for glucose and increased

A

Gluconeogenesis

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11
Q

In RBCs, 1,3 bisphosphoglycerate from GDP can be converted to

via the enzyme

A

2,3 bisphosphoglycerate
2,3 BPG

BPG mutase

with loss of ATP

this regulates oxygen delivery to tissue, binds to hemoglobin and decreases hemoglobin affinity to tissue

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12
Q

Deficiency of pyruvate kinase (Phosphoenolpyruvate -> Pyruvate) leads to decreased ability of RBCs to pump cations against concentration gradient and are unable to maintain homeostasis

A

Decreased ATP resulting in hemolysis

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13
Q

If there is enough oxygen, pyruvate is converted into

A

Acetyl coa

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14
Q

If there is insufficient oxygen, pyruvate is converted into

A

Lactate

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15
Q
9 year old/male
History of anemia due to enzyme deficiency
Splenomegaly
Conjunctival pallor
Elevated reticulocyte count
Hemolytic anemia
A

Pyruvate kinase converts PEP to pyruvate

If pyruvate kinase is deficient, it is unable to pump cations out of cell due to dec ATP leading to decreased homeostasis and HEMOLYSIS

Pyruvate kinase deficiency

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16
Q

First step in glycolysis

Irreversible

Uses up energy

A

Glucose -> glucose 6 phosphate by Hexokinase and Glucokinase

Addition of phosphate

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17
Q

Step 2:

Rearrangement of covalent bonds

A

Glucose 6 phosphate -> Fructose 6 phosphate by phosphoglucose isomerase

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18
Q

3rd step:

Irreversible

Second energy consumption step

First committed step

A

Fructose 6 phosphate -> Fructose 1,6 bisphosphate by Phosphofructokinase 1

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19
Q

Step 4:

Splitting of 6 to 3 carbon sugars

A

Fructose 1,6 bisphosphate -> GDAP (glyceraldehyde-3 phosphate) + DHAP (dihydroacetone phosphate)

by Fructose bisphosphate aldolase

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20
Q

Step 5

Isomerization

A

DHAP -> GDAP by triosephosphate isomerase

2 GDAP
2 ATPs consumed

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21
Q

Step 6:

Energy generation

Inhibited by Arsenic

A

GDAP -> 1,3 bisphosphoglycerate

by Glyceraldehyde phosphate dehydrogenase

2 NADH

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22
Q

Step 7:

Reversible

Energy generating

A

1,3 bisphosphoglycerate -> 3 phosphoglycerate

By Phosphoglycerate kinase

Transfer of phosphate
+ ATP

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23
Q

Step 8:

A

3 phosphoglycerate -> 2 phosphoglycerate

By Phosphoglycerate mutase

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24
Q

Step 9:

Lyase

Inhibited by Flouride

Dependent on Mg or Mn

A

2 phosphoglycerate -> Phosphoenolpyruvate

By Enolase

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25
Q

Step 10

Irreversible

Generation of ATP

A

Phosphoenolpyruvate -> Pyruvate

By Pyruvate kinase

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26
Q

End product of Glycolysis from 1 glucose molecule

A

2 NADH
4 ATP
2 Pyruvate

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27
Q

Glucose and maltose enters glycolysis by

A

Step 1 Glucose -> Glucose 6 phosphate

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28
Q

Starch, Galactose-1 phosphate, Galactose and Lactose enter glycolysis by

A

Second step: Glucose 6 -> Fructose 6 phosphate

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29
Q

Fructose, sucrose and mannose enters glycolysis at

A

Step 3: Fructose 6 phosphate -> Fructose 1,6 bisphosphate

30
Q

Glycerol and Glycerol 3 phosphate enters glycolysis via

A

Step 5: DHAP -> GHAP by triose phosphate isomerase

31
Q

Major pathway for glucose metabolism
Functions aerobically and anaerobically

Glucose -> pyruvate

A

Glycolysis

32
Q

Preliminary oxidation of glucose prior to complete oxidation in the Citric Acid Cycle

Generates ATP through substrate level phosphorylation and NADH through oxidative phosphorylation

A

Glycolysis

33
Q

ATP generation in glycolysis type of phosphorylation

A

Substrate level phosphorylation

34
Q

NADH generation in glycolysis type of phosphorylation

A

Oxidative phosphorylation

35
Q

Oxidation of glucose beyond pyruvate

A

Pyruvate dehydrogenase complex
Citric acid cycle
Respiratory chain

36
Q

Functions for the production of other substances like amino acids and fatty acids

Exercising muscle, cardiac muscle:
ischemia, hemolytic anemia, cancer, lactic acidosis

A

Glycolysis

37
Q

Occurs in cells with mitochondria
With adequate supply of oxygen

Product:

A

Aerobic glycolysis

2 NADPH from pyruvate

38
Q

Tissues without mitochondria
Without oxygen

Product

A

Anaerobic glycolysis

Lactate
NADH is reconverted to NAD+

39
Q

First committed step in glycolytic pathway

A

Fructose 6 -> Fructose 1,6 bisphosphate by PFK1

40
Q

Tissues that depend on glycolysis as their major mechanism for ATP

A

RBC, cornea, lens, regions of retina (lack mitochondria)

Kidney medulla, testis, leukocytes, white muscle fibers = few mitochondria almost totally dependent on glycolysis

41
Q

Absolute need for glucose via glycolysis

How many grams of glucose consumed per day

A

Brain

120 g

42
Q

Regulatory enzymes of glycolysis

A

Hexokinase (low km, low vmax all cells)/Glucokinase
PFK1
Pyruvate kinase

43
Q

PFK 1 is stimulated by

A

ADP
AMP
dec ATP/AMP ratio
Fructose 2,6 bisphosphate

44
Q

PFK1 is inhibited by

A
ATP
citrate
H ions
cAMP
inc ATP/AMP ratio
45
Q

Pyruvate kinase is stimulated by

A

Fructose 1 6 bisphosphate

46
Q

Pyruvate kinase is inhibited by

A

ATP
Alanine
Acetyl coa
Fatty acids

47
Q

Glucose 6 is broken down into 2 phosphoglyceraldehyde (GDAP and DHAP)

Requires two ATPs

A

Energy investment phase

48
Q
Phosphorylation of glucose
Isomerization of glucose
Phosphorylation of fructose-6-phosphate
Cleavage of fructose 1,6 bisphosphate
Isomerization of DHAP
A

Energy investment phase

49
Q

Used by most tissues
Low Km
Low Vm
Inhibition by Glucose-6-phosphate

A

Hexokinase

50
Q

Used in liver and B cells
High Km
High Vm
Not inhibited by Glucose-6-phosphate

A

Glucokinase

51
Q

Rate limiting step of Glycolysis
Irreversible reaction

Inhibited by high levels of ATP and citrate
Stimulated by high levels of AMP, fructose 2,6 bisphosphate (most potent) produced by phosphofructokinase 2

A

Fructose 6 -> Fructose 1,6 bisphosphate by PFK1

52
Q

Well fed state

Glucagon
Insulin

Substrate
Reaction

A

Dec glucagon
Inc insulin

Inc Fructose 2,6 bisphosphate
Inc glycolysis

53
Q

Starvation

Glucagon
Insulin

Substrate
Reaction

A

Inc glucagon
Dec insulin

Dec fructose 2,6 bisphosphate
Dec glycolysis

54
Q

Competes with inorganic phosphate as substrate for Glyceraldehyde 3 Phosphate Dehydrogenase

Complex that hydrolyzes to form 3-phosphoglycerate

Bypassing synthesis and dephosphrylation of 1,3 BPG leads to

A

Arsenic

Cell deprivation of energy

55
Q

Respiratory chain of NADH2

Inhibited by arsenic

A

Glyceraldehyde 3 phosphate -> 1,3 bisphosphoglycerate

by glyceraldehyde-3 phosphate dehydrogenase

56
Q

Dependent on presence of Mg or Mn
Redistributes the energy within 2-phosphoglycerate molecule

Catalyzes conversion of 2-phosphoglycerate molecule to Phosphoenolpyruvate PEP

A

Enolase

57
Q

Enolase which catalyzes conversion of 2 phosphoglycerate -> phosphoenolpyruvate is inhibited by

A

Flouride

58
Q

Inhibits enzymes which require Lipoic acid as coenzyme like pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase and glyceraldehyde 3 phosphate dehydrogenase

A

Arsenic

59
Q

85% of patients with genetic defects of glycolytic enzyme

2nd most common cause of enzymatic related hemolytic anemia

Restricted to erythrocytes
produces mild to severe hemolytic anemia

Severity depends on the degree of enzyme deficiency and on the extent to which individual compensates by synthesizing 2,3 BPG

Mutant enzyme with abnormal properties

A

Pyruvate kinase deficiency

60
Q

Phosphofructokinase deficiency

A

Tarui’s disease Type VII

Like McArdle but has hemolysis

61
Q

Feed forward regulation in liver

A

Pyruvate kinase activated by Fructose 1,6 bisphosphonate

Linking 2 kinase activities

Inc phosphofructokinase activity -> Inc Fructose 1,6 bisphosphate -> activated pyruvate kinase

62
Q

Covalent modulation of pyruvate kinase

A

Phosphorylation by cAMP dependent protein kinase leads to INactivation of protein kinase in liver

Low blood glucose levels -> glucagon secretion -> inc intracellular level of cAMP -> phosphorylation and inactivation of Pyruvate kinase -> PEP unable to continue glycolysis enters gluconeogenesis

Dephosphorylation of pyruvate kinase by phosphoprotein phosphatase -> enzyme reactivation

63
Q

Hormonal regulation of Glycolysis

Increase in Insulin leads to activation of
And dec in glucagon

A

Glucokinase
Phosphofructokinase
Pyruvate kinase

64
Q

inc NADH production exceeds oxidative capacity of the respiratory chain

inc NADH/NAD+ ratio favors

A

Reduction of pyruvate to lactate

anaerobic glycolysis

65
Q

Intense exercise: lactate accumulation in pH and drop in intracellular pH leading to

Lactate can diffuse into blood stream -> gluconeogenesis (liver)

A

Muscle cramps

66
Q

Depends on the relative intracellular concentrations of pyruvate and lactate
NADH/NAD ratio

Heart and liver lower NADH/NAD ratio than exercising muscles and can oxidize lactate to pyruvate

In the liver, pyruvate is converted to

In the heart, lactate is exclusively oxidized to

A

Glucose or oxidized in the TCA

CO2 and H2O via citric acid cycle

67
Q

Occur with collapse of the circulatory system
Failure to bring adequate amounts of oxygen to tissues -> impaired oxidative phosphorylation -> dec ATP synthesis

Solution: use of anaerobic system

Oxygen debt: excess oxygen required to recover from a period when the availability of oxygen has been inadequate

A

Lactic acidosis

68
Q

Respiratory chain of NADH

GDAP -> 1,3 bisphosphoglycerate by G3P dehydrogenase

yields how many ATPs

A

5

69
Q

Substrate level phosphorylation

1,3 bisphosphoglycerate -> 3 phosphoglycerate by phosphoglycerate kinase

yields how many ATPs

A

2

70
Q

Substrate level phosphorylation

Phosphoenolpyruvate -> pyruvate
by pyruvate kinase

yields

A

2 ATPs

71
Q

Anaerobic glycolysis occurs because

A

there is no net formation of NADH (oxygen is required to reoxidize NADH formed during oxidation of GDAP)