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POM (Principles of Medicine) > Cell Metabolism > Flashcards

Cell Metabolism Flashcards

1
Q

3 main stages of cellular metabolism

A
  1. Glycolysis
  2. TCA Cycle (tricarboxylic acid cycle)
  3. Oxidative phosphorylation
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2
Q

Definition of:

Glycolysis

A

Oxidation of glucose within the cystol of individual cells, generating ATP & NADH

substrate level phosphorylation of respiratory substrate glucose to synthesize pyruvate, ATP, NADH.

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3
Q

Definition of:

TCA cycle

A

Further oxidation of small molecules within the mitochondria of individual cells, generating ATP, NADH, FADH2 and waste products

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4
Q

Definition of:

Oxidative phosphorylation

A

Generation of ATP within the mitochondria by the reduction of O2 to H2O
(where the bulk of cellular ATP is generated)

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5
Q

Activation Energy barrier

A

large and needs to be overcome for the combustion of glucose & the free energy is released as heat

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6
Q

Glucose metabolism

A

Free energy liberated is invested in carries molecules such as ATP.
Relatively small activation energies overcome by enzymes & body temp

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7
Q

How many ATP molecules are made per glucose molecule?

A

38

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8
Q

6 types of reactions in metabolism

A
  1. Oxidation reduction
  2. Ligation requiring ATP cleavage
  3. Isomerization
  4. Group transfer
  5. Hydrolytic
  6. Addition or removal of functional groups
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9
Q

Definition of:

Oxidation-reduction

A

Electron transfer

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10
Q

Definition of:

Ligation requiring ATP cleavage

A

Formation of covalent bonds

i.e. carbon-carbon bonds

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11
Q

Definition of:

Isomerization

A

Rearrangement of atoms to form isomers

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12
Q

Definition of:

Group transfer

A

Transfer of a functional group from one molecule to another

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13
Q

Definition of:

Hydrolysis

A

Cleavage of bonds by the addition of water

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14
Q

Definition of:

Addition or removal of functional groups

A

Addition of functional groups to double bonds or their removal to form double bonds

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15
Q

Glycolysis end products

A

1 x 6 carbon molecule(Glucose) —(2 x ATP)—> 2 x 3 carbon molecules(Pyruvate)

(probably a throwback to the pathways used by prehistoric anaerobic bacteria)

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16
Q

2 main concepts of glycolysis

A
  1. Formation of a high energy compound
    (involves the investment of E in the form of ATP)
  2. Splitting of a high energy compound
    (produces E in the form of ATP generation)
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17
Q

Glycolysis STEP 1

A

Glucose is phosphorylated into glucose-6-phosphate ( & H+)

enzyme: HEXOKINASE
- one ATP is turned into ADP
- irreversible
- traps glucose inside the cell bc of (-)ve charge
GROUP TRANSFER

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18
Q

Glycolysis STEP 2

A

Glucose-6-phosphate is turned into fructose-6-phosphate

enzyme: PHOSPHOGLUCOSE ISOMERASE
- aldose to ketose
- fructose can then be split into equal halves when cleaved later
ISOMERISATION

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19
Q

Which enzyme catalyses the phosphorylation of glucose into glucose-6-phosphate?

A

Hexokinase

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20
Q

Which enzyme catalyses the isomerization of glucose-6-phosphate into fructose-6-phosphate?

A

Phosphoglucose isomerase

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21
Q

Glycolysis STEP 3

A

Fructose-6-phosphate is phosphorylated by ATP into fructose-1,6-bisphosphate

enzyme: PHOSPHOFRUCTOKINASE
- regulation of enzyme -> entry of sugars into glycolysis pathway
GROUP TRANSFER

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22
Q

Which enzyme catalyses the phosphorylation of fructose-6-phosphate into fructose-1,6-bisphosphate?

A

phosphofructokinase

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23
Q

Glycolysis STEP 4

A

Fructose-1,6-bisphosphate is hydrolysed to glyceraldehyde-3-phosphate & dihydroxyacetone phosphate

enzyme: ALDOLASE
- 2 high energy compounds
HYDROLYTIC

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24
Q

Which enzyme catalyses the hydrolysis of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate & dihydroxyacetone phosphate?

A

aldolase

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25
Q

Glycolysis STEP 5

A

Dihydroxyacetone phosphate is turned into glyceraldehyde-3-phosphate

enzyme: TRIOSE PHOSPHATE ISOMERASE (TPI)
- deficiency in TPI is the only glycolytic enzymopathy that is fatal- most sufferers die within 6 years
ISOMERISATION

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26
Q

Which enzyme catalyses the isomerisation of Dihydroxyacetone to glyceraldehyde-3-phosphate?

A

triose phosphate isomerase

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27
Q

Glycolysis STEP 6

A

2x glyceraldehyde-3-phosphate is dehydrogenated (oxidation) and phosphorylated into 1,3-bisphosphoglycerate

enzyme: GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
- NAD+ –> NADH
-ATP –> ADP
REDOX & GROUP TRANSFER

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28
Q

Which enzyme catalyses the oxidation & phosphorylation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate?

A

glyceraldehyde-3-phosphate dehydrogenase

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29
Q

Glycolysis STEP 7

A

1,3-bisphosphoglycerate turned into 3-phosphoglycerate

enzyme: PHOSPHOGLYCERATE KINASE
- ADP –> ATP
GROUP TRANSFER

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30
Q

Which enzyme catalyses the conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate?

A

phosphoglycerate kinase

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31
Q

Glycolysis STEP 8

A

3-phosphpoglycerate is converted to 2-phosphoglycerate

enzyme: PHOSPHOGLYCERATE MUTASE
-shuffling of the phosphate group from the 3 to the 2 position (by removal and addition of phosphoryl groups)
ISOMERISATION

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32
Q

Which enzyme catalyses the isomerisation of 3-phosphpoglycerate to 2-phosphoglycerate?

A

phosphoglycerate mutase

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33
Q

Glycolysis STEP 9

A

2-phosphoglycerate is converted to phosphoenolpyruvate + H2O

enzyme: ENOLASE
-dehydration reaction (removes H and OH)
GROUP REMOVAL

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34
Q

Which enzyme catalyses the conversion of 2-phosphoglycerate into phosphoenolpyruvate?

A

enolase

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35
Q

Glycolysis STEP 10

A

Phosphoenolpyruvate is turned into pyruvate

enzyme: PYRUVATE KINASE
- ADP –> ATP
GROUP TRANSFER

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36
Q

Which enzyme catalyses the conversion of phosphoenolpyruvate into pyruvate?

A

pyruvate kinase

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37
Q

The net result of glycolysis?

A
  1. net gain of 2 ATP

2. 2 NADH

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38
Q

where does glycolysis take place?

A

Cellular cytoplasm

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39
Q

How many ATP molecules are produced during glycolysis?

A

4
2 via 1,3-bisphosphoglycerate
2 via phosphoenolpyruvate

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40
Q

Destination of NADH (aerobic conditions)

A

pass through outer mitochondrial membrane into the ETC

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41
Q

Destination of pyruvate? (aerobic conditions)

A

Actively transported into the mitochondrial matrix, where it undergoes the link reaction

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42
Q

What ion is required to enable phosphorylation?

A

Magnesium Ion

43
Q

Why is mg required for the initial phosphorylation of glucose?

A

(+)vely charged ion shields negative ATP phosphate group

44
Q

What type of enzyme is phosphofructokinase?

A

Allosteric enzyme

pace of glycolysis is dependent on enzyme activity, allosterically controlled by ATP
ATP is an inhibitor

45
Q

Why is symmetrical configuration of hexose-bisphosphate useful?

A

High E compound

46
Q

What is mutase?

A

An enzyme that catalyses the intramolecular shift of a chemical group (phosphoryl)

47
Q

What are the advantages of enol phosphates? (phosphoenolpyruvate)

A

Dehydration elevates the group-transfer potential of the phosphoryl group. High phosphoryl transfer potential, thereby making it easier for the conversion into pyruvate & the generation of ATP

48
Q

What is the fate of pyruvate under anaerobic conditions?

A

O2 cannot be the final e- acceptor
Pyruvate is reduced to lactate by NADH to continue substrate level phosphorylation via glycolysis

enzyme: LACTATE DEHYDROGENASE
- NADH –> NAD+ (reoxidation)
DEHYDROGENATION

49
Q

Which enzyme catalyses the conversion of pyruvate to lactate?

A

lactate dehydrogenase

50
Q

What is the benefit of pyruvate –> lactate conversion

A

Reoxidises NADH to continue glycolytic ATP synthesis

Lactate is transported to the liver, converted back to pyruvate

51
Q

Overall reaction for anaerobic respiration

A

Glucose +2 Pi +2 ADP–> 2 Lactate + 2 ATP + 2 H20

52
Q

Fate of pyruvate under aerobic conditions?

A

AT to mitochondrial matrix
Link Reaction
Dehydrogenated & decarboxylated to an acetate
Combines with Coenzyme-A (CoA) to form acetyl CoA

53
Q

What is the fate of pyruvate?
(except anaerobic respiration)
yeast

A
  1. Pyruvate converted to acetaldehyde

enzyme: PYRUVATE DECARBOXYLASE
- H+ –> CO2
DECARBOXYLATION

  1. Acetaldehyde reduced to ethanol

enzyme: ALCOHOL DEHYDROGENASE
- NADH + H+ –> NAD+
REDUCTION

54
Q

What is Creatine phosphate?

A
  • acts as a source or buffer for ATP production
  • doubles the time by which the cell is independent of respiration
  • bonds: phosphoanhydride bonds
55
Q

creatine phosphate reaction

A

Creatine phosphate is converted to creatine + ATP

enzyme: CREATINE KINASE
- ADP + H+ –> ATP
very thermodynamically favourable

56
Q

Acetyl CoA generation

in the mitochondria

A

pyruvate + HS-CoA –> acetyl CoA + CO2

enzyme: PYRUVATE DEHYDROGENASE COMPLEX
- NAD+ –> NADH
- acetyl group is ligated to enzyme CoA & this carbonyl group here is lost as CO2

57
Q

Structure of Acetyl CoA

A

thioester bond is a high-energy linkage– readily hydrolysed, enabling acetyl CoA to donate the acetate (2C) to other molecules

58
Q

Pyruvate dehydrogenase complex consists of ..?

A

pyruvate dehydrogenase & pyruvate decarboxylase

59
Q

Overall equation for the link reaction?

A

Pyruvate + NAD +CoA —> AcetylCoA + CO2 +NADH

60
Q

Products of the Link reaction per glucose molecule

A

2 CO2
2 acetyl-CoA
2 NADH

61
Q

What is Beri Beri?

A

Thiamine deficient disease, damaged PNS

Weakness of musculature

62
Q

What is thiamine pyrophosphate?

A

Cofactor to the pyruvate dehydrogenase (PHD)

Easily deprotonated into a carbanion attacks pyruvate

63
Q

What is the function of thiamine pyrophosphate?

A

Assists in the decarboxylation of pyruvate

64
Q

Where does the Krebs cycle occur?

A

The mitochondrial fluid matrix

65
Q

Role of the role of the krebs cycle?

A

convert the acetate group to CO2 & H

complete oxidation of glucose

66
Q

Krebs Cycle STEP 1

ocxaloacetate–>

A

Coenzyme A transfers the 2-carbon acetate to a 4 carbon compound (OXALOACETATE) to form citrate

67
Q

Krebs Cycle STEP 2

citrate–>

A

citrate –> isocitrate(6C)

68
Q

Krebs Cycle STEP 3

isocitrate–>

A

citrate –> alpha-ketoglutarate (5C)

  • NAD+ –> NADH
    waste: CO2
69
Q

Krebs Cycle STEP 4

a-ketoglutarate–>

A

a-ketoglutarate–> succinyl-CoA (4C)

  • NAD+ –> NADH
    waste: CO2
70
Q

Krebs Cycle STEP 5

succinyl-CoA–>

A

Succinyl-CoA –> succinate (4C)

GTP released

71
Q

Krebs Cycle STEP 6

succinate–>

A

succinate–> fumerate(4C)

-FAD –> FADH2

72
Q

Krebs Cycle STEP 7

fumerate–>

A

fumerate –> malate (4C)

73
Q

Krebs Cycle STEP 8

malate–>

A

malate –> oxaloacetate (4C)

-NAD+ –> NADH

74
Q

Describe the krebs cycle pathway:

A

citrate –> isocitrate –> alpha-ketoglutarate –> succinyl-CoA –> succinate –> fumarate –> malate –> oxaloacetate

75
Q

How many molecules of CO2 is released by one turn of the Krebs Cycle?

A

2 molecules

76
Q

What are the products of the krebs cycle?

A 
2 CO2
3 NADH
1 FADH2
1 ATP
1 GTP
77
Q

How many molecules of H2O required for one turn?

A

2

78
Q

What is a transamination reaction?

A

process by which amino acids are removed & transferred to acceptor keto acids

79
Q

Which molecules arise from the transamination of a.a.?(7)

A 
Pyruvate
acetyl-CoA
acetoacetyl-CoA
alpha-ketoglutarate 
succinyl CoA
fumarate
oxaloacetate
80
Q

Tricarboxylic acid cycle (TCA) waste products?

A

amino group is removed(excreted as urea)

carbon skeleton is funnelled into the production of glucose or Krebs Cycle

81
Q

Which 3 a.a. are susceptible for phosphorylation?

A

Serine
threonine
tyrosin (OH) group

82
Q

What is formed from an alanine + ketoacid?

A

Pyruvate & glutamate

enzyme: TRANSAMINASE
- switching amino group from one molecule to another
GROUP TRANSFER

83
Q

Why is the glycerol phosphate shuttle used?

A

This is bc the inner mitochondrial membrane is relatively impermeable to NADH and NAD+ (Glycolytic derived)
Electrons are transferred to glycerol-3-phosphate into the mitochondrial membrane
enzyme: CYTOPLASMIC GLYCEROL-3-PHOSPHATE DEHYDROGENASE

84
Q

What molecules does NADH transfer electrons to?

in glycerol phosphate shuttle

A

Dihydroxyacetone phosphate

85
Q

Where is glycerol-3-phosphate located?

A

outer mitochondrial membrane

86
Q

What happens to dihydroxyacetone phosphate upon electron donation?

A

Forms glycerol-3-phosphate

87
Q

Which enzyme catalyses the transfer of e-?

A

Cytosolic glycerol-3-phosphate dehydrogenase

88
Q

What is the destination of glycerol-3-phosphate within the inner mitochondrial membrane?

A

The e- pair is donated from glycerol-3-phosphate to FAD prophetic group of the mitochondrial glycerol dehydrogenase to produce dihydroxyacetone phosphate

89
Q

How is dihydroxyacetone phosphate reformed?

A

Oxidation of glycerol-3-phosphate diffuses back into the cytosol to continue the shuttling process

90
Q

What is subsequently formed via the glycerol phosphate shuttle?

A

FADH2

91
Q

Where does the malate-aspartate shuttle occur?

A

within the heart and liver cells

92
Q

What molecules does NADH transfer electrons to in the malate-aspartate shuttle?

A

oxaloacetate

93
Q

What molecule is oxaloacetate converted into upon reduction via NADH ( malate-aspartate shuttle)?

A

Malate (Malate dehydrogenase catalyzes redox)

94
Q

What enzyme catalyzes the reduction of oxaloacetate in the malate-aspartate shuttle?

A

Malate dehydrogenase

95
Q

What is the destination of malate?

A

Transverses into the inner mitochondrial membrane, and is reoxidised by NAD+ forming NADH & oxaloacetate

96
Q

How is the formed oxaloacetate be transported across the inner mitochondrial membrane to cytosol?

A

oxaloacetate transaminated into aspartate and alpha ketoglutarate via glutamate

97
Q

Reaction of oxaloacetate & glutamate?

A

oxaloacetate + glutamate –> aspartate + alpha-ketoglutarate

enzyme: ASPARTATE-TRANSAMINASE

98
Q

What is the fate of aspartate in the malate-aspartate shuttle?

A

Passes through the inner mitochondrial membrane into the cytosol, reacts with ketoacid to form glutamate & oxaloacetate

99
Q

How many ATP molecules are produced by the reoxidation of one NADH?

A

3

100
Q

How many ATP molecules are produced by the reoxidation of one FADH2?

A

2

101
Q

Total ATP produced from the krebs Cycle?

A

3 x 3 + 1 x 2 + 1 = 12 ATP

102
Q

What does a kinase enzyme catalyse?

A

Transfer a phosphate group to a substrate

103
Q

What is substrate level phosphorylation?

A

Direct transfer of a high-energy phosphate group to ADP

104
Q

What is lactate dehydrogenase? (LDH)

A

released when cells die into the circulation, hence serum levels of LDH, in diagnostic of tissue damage in situations such as a stroke & MI

POM (Principles of Medicine) (17 decks)

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