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Biochemistry, genetics, and metabolism > Glycolysis > Flashcards

Glycolysis Flashcards

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1
Q

How many steps in glycolysis?

A

10, employed by all tissues to break down glucose and provide energy in the form of ATP and intermediates for other pathways

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2
Q

what types of sugars can be converted to glucose?

A

almost all of them

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3
Q

anaerobic pathway

A

glycolysis does not require O2 to proceed

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4
Q

Where does glycolysis take place?

A

cytosol

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5
Q

What does the fate of pyruvate in human cells depend on?

A
  1. whether or not an adequate supply of oxygen is available

2. mitochondria are present

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6
Q

aerobic glycolysis

A

in cells with sufficient O2 and mitochondria

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7
Q

What is the end product of in aerobic glycolysis?

A

pyruvate

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8
Q

NADH during glycolysis

A

oxidized to NAD+ via oxidative phosphorylation where O2 is the final electron acceptor

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9
Q

What is require for glycolysis to proceed?

A

NAD+

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10
Q

anaerobic glycolysis

A

in cells that lack mitochondria or have insufficent O2 supply

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11
Q

what is the final electron acceptor for anaerobic glycolysis?

A

pyruvate

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12
Q

What allows for the regeneration of NAD+ in anaerobic glycolysis?

A

pyruvate being converted into lactate via lactic acid fermentation

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13
Q

How does glucose enter cells?

A
  • CANNOT diffuse directly into cells
  • Na+ independent facilitated diffusion transport
  • Na+ monosaccharide cotransporter system (SGLT)
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14
Q

GLUT mechanism

A
  • spans membrane
  • ATP-independent (passive transport)
  • changes conformation upon glucose binding which allows to cross membrane
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15
Q

Which GLUT are always in plasma membrane?

A

1,2,3

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16
Q

GLUT isoforms

A
  • tissue specific
  • specific regulation
  • specificity for substrate (GLUT-5, fructose)
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17
Q

GLUT-1

A
  • most tissues, abundant in brain and RBC

- Basal uptake of glucose

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18
Q

GLUT-2

A
  • Liver, pancreatic beta-cells

- glucose uptake and release by liver; beta-cell glucose sensor

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19
Q

GLUT-3

A
  • most tissues, abundant in neurons

- basal uptake of glucose

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20
Q

GLUT-4

A
  • skeletal muscle, adipose tissue

- insulin stimulated glucose uptake; stimulated by exercise in muscle

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21
Q

Which GLUT is not always on plasma membrane?

A

4

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22
Q

SGLT mechanism

A
  • transport glucose against its can gradient by co-transporting Na+ down its gradient (active)
  • requires energy supplied by an Na+, K+-ATPase that pumps Na+ outside the cell to create the Na+ gradient
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23
Q

SGLT location

A
  • epithelial cells of the intestines
  • renal tubules
  • choroid plexus (BBB)
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24
Q

significance of phosphorylation of glucose to glucose 6-phosphate

A
  • once phosphorylated, glucose cannot cross membrane (+deltaG, NEEDS ATP)
  • there are no transported for G-6-P
  • therefor phosphorylation traps the molecule inside the cell because molecule is now more polar.
  • overall delta G is negative
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25
Q

hexokinase

A
  • phosphorylation of glucose to glucose 6-phosphate
  • found in most tissues
  • broad substrate specificity
  • inhibited by product
  • high affinity for glucose (low Km)
  • low Vmax-cannot trap glucose inside the cells
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26
Q

glucokinase

A
  • phosphorylation of glucose to glucose 6-phosphate
  • similar to hexokinase (not specific)
  • has much higher Km
  • high Vmax-allows liver to effectively clear up glucose from the blood
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27
Q

glucokinase location

A
  • phosphorylation of glucose to glucose 6-phosphate

- found only in hepatocytes and pancreatic beta cells

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28
Q

What inhibits glucokinase?

A

-phosphorylation of glucose to glucose 6-phosphate

indirectly inhibited by fructose-6-phosphate

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29
Q

What stimulates glucokinase?

A
  • phosphorylation of glucose to glucose 6-phosphate

- indirectly stimulated by glucose

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30
Q

mutations of glucokinase

A

cause a rare form of diabetes called maturity-onset diabetes of the young (MODY)

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31
Q

First step of glycolysis

A

phosphorylation of glucose to glucose 6-phosphate

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32
Q

second step of glycolysis

A

-isomerization of glucose 6-phosphate

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33
Q

significance of isomerization of glucose 6-phosphate

A
  • aldo-keto isomerization
  • readily reversible
  • NOT rate limiting
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34
Q

enzyme of isomerization of glucose 6-phosphate

A

phosphoglucose isomerase

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35
Q

What is the third step of glycolysis?

A

phosphorylation of fructose 6-phosphate

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36
Q

What is the rate determining step of glycolysis?

A

phosphorylation of fructose 6-phosphate

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37
Q

What is the most important step of glycolysis?

A

phosphorylation of fructose 6-phosphate

38
Q

significance of phosphorylation of fructose 6-phosphate

A
  • irreversible
  • rate-limiting step
  • the most important control point
39
Q

enzyme involved with phosphorylation of fructose 6-phosphate

A

phosphofruktokinase-1 (PFK-1)

40
Q

PFK-1 activity

A

-requires ATP
-regulated by
-energy status of the cell
-fructose 2,6-bisphosphate produced by
PFK 2

41
Q

AMP being a positive regulator

A

cannot have high amounts of AMP and ATP. if ATP is low, AMP is high

42
Q

2,6-bis-phosphate produced by PFK-2 as a positive regulator

A

2 different binding sites for different affinity for ATP

  • allosteric site
  • atp will bind to allosteric site when there’s a lot
43
Q

PFK1 regulation by energy status of the cell

A

allosterically inhibited by ATP and citrate; activated by high AMP levels

negative feedback

44
Q

4th step of glycolysis

A

cleavage of fructose 1,6-bisphosphate

45
Q

significance of cleavage of fructose 1,6-bisphosphate

A

cleaves one 6-carbon sugar to form two 3-carbon sugars

46
Q

enzyme of the cleavage of fructose 1,6-bisphosphate

A

aldolase

47
Q

what does aldolase do?

A

cleaves one 6-carbon sugar to form 2 3-carbon sugars

48
Q

whats the 5th step of glycolysis?

A

isomerization of dihydroacetone-P (DHAP)

49
Q

significance of isomerization of dihydroacetone-P (DHAP)

A
  • interconverts two 3-carbon sugars
  • necessary for he glycolysis for proceed
  • reversible
  • dependent on cxn of products and substrates
50
Q

enzyme associated with isomerization of dihydroacetone-P (DHAP)

A

triose phosphate isomerase

51
Q

What is the 6th step of glycolysis?

A

oxidation of glyceraldehyde 3-phosphate

52
Q

significance of the oxidation of glyceraldehyde 3-phosphate

A
  • coupled to the reduction of NAD+ to NADH
  • attachment of a phosphate group to the carboxyl group to form 3-BPG
  • this Pi will drive the synthesis of ATP in the next reaction
53
Q

enzyme associated with the oxidation of glyceraldehyde 3-phosphate

A

glyceraldehyde 3-P dehydrogenase

54
Q

glyceraldehyde 3-P dehydrogenase

A
  • removes electrons

- inhibited by pentavalent arsenic

55
Q

step 6.1 of glycolysis

A

alternating reaction in RBCs: synthesis of 2,3bisphosphoglycerate

56
Q

Where does synthesis of 2,3bisphosphoglycerate happen?

A

RBC only

57
Q

synthesis of 2,3bisphosphoglycerate

A
  • 2,3-BPG is in trace levels in most cells
  • in RBCs is VERY HIGH and serves to increase O2 delivery
  • this step is a modification of glycolysis found in RBCs only
58
Q

step 7 of glycolysis

A

synthesis of 3-phosphoglycerate producing ATP

59
Q

significance of synthesis of 3-phosphoglycerate producing ATP

A
  • phospho- group is directly transferred to ADP to produce ATP (substrate level phosphorylation)
  • reversible under physiological conditions (unusual for kinases)
60
Q

enzyme involved with synthesis of 3-phosphoglycerate producing ATP

A

phosphoglycerate kinase

61
Q

phosphoglycerate kinase

A
  • synthesis of 3-phosphoglycerate producing ATP
  • unusual kinase
  • transfers phosphate group
  • actually dephosphorylates too
  • irreversible
62
Q

what is the 8th step of glycolysis?

A

shift the phosphate group from carbon 3 to carbon 2

63
Q

what is the enzyme to shift the phosphate group from carbon 3 to carbon 2

A

phosphoglycerate mutase

64
Q

What is the ninth 9th step of glycolysis

A

dehydration of 2-phosphoglycerate

65
Q

what is the significance of dehydration of 2-phosphoglycerate

A
  • produce PEP which contain high energy phosphate

- substrate level phosphorylation

66
Q

what is the enzyme associated with the dehydration of 2-phosphoglycerate

A

enolase

67
Q

what is the 10th step of glycolysis?

A

formation of pyruvate and production of ATP

68
Q

what is the significance of the formation of pyruvate and production of ATP

A
  • the 3rd irreversible action
  • high energy enos-phosphate is used to produce ATP from ADP
  • substrate level phosphorylation
69
Q

what is the enzyme used in the formation of pyruvate and production of ATP

A

pyruvate kinase (PK)-complex regulation

70
Q

Pyruvate kinase (PK)-complex regulation

A
  • formation of pyruvate and production of ATP
  • feedforward regulation by fructose 1,6-bisphosphate (allosteric activator)
  • phosphorylation via cAMP-dependent PKA
71
Q

Deficiency in pyruvate and ATP

A
  • affects RBC function mostly

- they don’t have mitochondria and can result in hemolytic anemia

72
Q

glucagon

A
  • fasting

- phosphorylation=inactive pyruvate kinase

73
Q

insulin

A
  • well-fed

- dephosphorylation=active pyruvate kinase

74
Q

PK regulation via cAMP-dependent PKA and hormonal status

A
  • pyruvate kinase only active in liver in well-fed state (high glucose availability)
  • this is necessary in the liver because the liver will synthesize glucose (gluconeogenesis) during fasting
75
Q

Fate of Pyruvate

A

-in order for glycolysis to proceed, NAD+ has to be regenerated

76
Q

fate of pyruvate if there is sufficient O2 and mitochondria available

A
  • will be done through the ECT

- pyruvate will be converted into acetyl CoA in the mitochondrial matrix

77
Q

fate of pyruvate if there is a lack of O2 and/or mitochondria

A
  • reduced to lactate by lactate dehydrogenase (REVERSIBLE)

- this will regenerate NAD+

78
Q

Fate of lactate and human health

A

-lactate is normal in RBCs and exercising muscle

79
Q

excessive exercise

A

build up of lactate in muscle cells that results in lowered pH leading cramping

80
Q

lack of O2 in tissues

A
  • causes excessive lactate buildup inside cells
  • denatures enzymes
  • death of cells
  • MI, pulmonary embolism, uncontrolled hemorrhage
81
Q

lactic acidosis

A
  • excessive lactate production
  • lactate reaching the plasma builds to excessive levels
  • lowers the pH of the blood
82
Q

alternative fates of pyruvate

A
  1. oxidative decarboxylation of pyruvate to acetyl coA
  2. carboxylation of pyruvate to oxaloacetate
  3. reduction to ethanol (not in humans)
83
Q

oxidative decarboxylation of pyruvate to acetyl coA

A
  • alternative fate of pyruvate
  • enzyme: pyruvate dehydrogenase complex
  • important in tissues with high oxidative capacity (cardiac muscle)
  • irreversible step
84
Q

carboxylation of pyruvate to oxaloacetate

A
  • alternative fate f pyruvate
  • enzyme: pyruvate carboxylase
  • can be used for gluconeogensis
  • to replenish TCA cycle intermediates
85
Q

Net energy yields in anaerobic glycolysis

A

2 ATP + 2 NADH per 1 glucose

NADH oxidation does not yield additional ATP

86
Q

Net energy yields for aerobic glycolysis

A
  • 2 ATP + 2 NADH per 1 glucose
  • oxidation of NADH through the ETC, we will get an additional 3 ATP per molecule NADH
  • net yield about 8 ATP per 1 glucose
87
Q

What is under the transcriptional control in he liver?

A

the three key enzymes catalyzing the irreversible steps of glycolysis (glucokinase, PFK, pyruvate kinase)

88
Q

what stimulates the transcription of the gene of the irreversible enzymes?

A

insulin

89
Q

what inhibits the transcription of the gene of the irreversible enzymes?

A

glucagon

90
Q

prolonged higher insulin levels

A
  • high carb diet, insulin therapy for diabetic, hyperinsulinemic pt
  • results in net increase in the amount of these key enzymes
91
Q

prolonged higher glucagon levels

A
  • prolonged fasting, low carb, untreated type 1 diabetes

- result in a net decrease in these key enzymes

Biochemistry, genetics, and metabolism (11 decks)

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