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POM (Principles of Medicine) > Cellular Metabolism > Flashcards

Cellular Metabolism Flashcards

1
Q

What 6 types of metabolic reactions are present?

A 
Oxidation-reduction 
Ligand requiring ATP cleavage
Isomerization 
Group transfer
Hydrolytic
Addition or removal of functional groups
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2
Q

What are oxidation-reduction reactions?

A

Electron transfer

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3
Q

What are ligation reactions?

A

Formation of covalent bonds

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4
Q

What are isomerization reactions?

A

Rearrangement of atoms to form isomers

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5
Q

What are group transfer reactions?

A

Transfer of a functional group from one molecule to another

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6
Q

What are hydrolytic reactions?

A

Cleavage of a bond by the addition of water

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7
Q

What are the reduction reactions?

A

Addition of electrons or the addition of hydrogen

Removal of oxygen

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8
Q

What are oxidation reactions?

A

Addition of oxygen/removal of hydrogen

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9
Q

Name the hydrogen acceptors present within the electron transport chain:

A

Flavoprotein, coenzyme Q, cytochrome b,c,a

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10
Q

What is NAD?

A

Nicotinamide adenine dinucleotide. Coenzyme hydrogen acceptor.
Oxidised form is denoted as NAD+

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11
Q

What is FAD?

A

Flavin adenine dinucleotide

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12
Q

What is the first step of glycolysis?

A

Glucose is phosphorylated into glucose-6-phosphate by hexokinase (Phosphoryl transfer)

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13
Q

Which enzyme catalyses the initial phosphorylation of glucose?

A

Hexokinase-4

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14
Q

What is step 2 of glycolysis?

A

Glucose-6-phosphate undergoes isomerization reactions into fructose-6-phosphate, under the action of phosphoglucoisomerase (Aldose to ketose)

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15
Q

What enzyme catalyses the isomerization of glucose-6-phosphate –> Fructose-6-phosphate?

A

Phosphoglucoisomerase

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16
Q

What is step 3 of glycolysis?

A

Fructose-6-phosphate is phosphorylated by ATP into fructose-1,6-bisphosphate by phosphofructokinase (group transfer)

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17
Q

How is fructose-6-phosphate phosphorylated into fructose-1,6-bisphosphate?

A

Phosphofructokinase

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18
Q

What is step 4 of glycolysis?

A

Fructose-1,6-bisphosphate is hydrolyzed into two molecules of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate (hydrolytic cleavage)

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19
Q

What molecules is fructose-1,6-bisphosphate hydrolysed into?

A

Glyceraldehyde-3-phosphate

Dihydroxyacetone phosphate

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20
Q

What happens to dihydroxyacetone phosphate?

A

Undergoes isomerisation reaction into glyceraldehyde-3-phosphate via triosephosphate isomerase (TPI)

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21
Q

What is step 6 of glycolysis (Glyceraldehyde-3-phosphate –>)?

A

Dehydrogenated and phosphorylated by group transfer into 1,3-bisphosphoglycerate
NAD+ is the hydrogen carrier,oxidises the molecule resulting in reduced NAD

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22
Q

How is reduced NAD formed through the conversion of glyceraldehyde-3-phosphate into 1,3bisphosphoglycerate?

A

Dehydrogenation of glyceraldehyde-3-phosphate reduces NAD into reduced NAD
Oxidation-reduction reaction

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23
Q

What happens to 1,3-bisphosphoglycerate?

A

Under the action of phosphoglycerate kinase (group removal) into 3-phosphoglycerate (ADP is phosphorylated into ATP)

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24
Q

What enzyme catalyses the convention of 1,3bisphosphoglycerate into 3-phosphoglycerate?

A

Phosphoglycerate kinase

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25
Q

What is the destination of 3-phosphoglycerate?

A

3-Phosphoglycerate undergoes isomerization reaction into 2-phosphoglycerate by phosphoglycerate mutase

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26
Q

What enzyme isomerises 3-phosphoglycerate into 2-phosphoglycerate?

A

Phosphoglycerate mutase

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27
Q

What is the destination of 2-phosphoglycerate?

A

2-phosphoglycerate is converted into phosphoenolpyruvate by enolase (dehydration, water is removed)

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28
Q

What converts 2-phosphoglycerate into phosphoenolpyruvate?

A

Enolase

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29
Q

What type of reaction is the conversion of 2-phosphoglycerate into phosphoenolpyruvate?

A

Dehydration (water is removed)

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30
Q

What is the destination of phosphoenolpyruvate?

A

Phosphoenolpyruvate is converted into pyruvate by pyruvate kinase. ATP is formed

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31
Q

Where does glycolysis occur?

A

Cellular cytoplasm

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32
Q

What is glycolysis?

A

Substrate level phosphorylation of respiratory substrate glucose to synthesize pyruvate, ATP, and reduced NAD to generate ATP

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33
Q

Why is glucose phosphorylated?

A

Phosphorylation makes glucose more reactive, therefore unable to pass through cell membrane (negative charge)
Stored within cell
Regulated by phosphofructokinase

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34
Q

How many gross ATP molecules is produced via glycolysis?

A

4
2 via 1,3bisphosphoglycerate –> 3-bisphosphoglycerate
2 via phosphoenolpyruvate –> pyruvate

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35
Q

How many net ATP is produced?

A

2

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36
Q

What is the destination of the 2 NADH molecules under aerobic conditions?

A

Pass through the outer mitochondrial membrane into the electron transport chain

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37
Q

What is the destination of pyruvate under aerobic conditions?

A

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

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38
Q

What is released from glucose phosphorylation into glucose-6-phosphate?

A

Proton

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39
Q

What ion is required to enable phosphorylation?

A

Magnesium ion

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40
Q

Why is magnesium required for the initial phosphorylation of glucose?

A

Positively charged ion shields negative ATP phosphate group.

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41
Q

What type of enzyme is phosphofructokinase?

A

Allosteric enzyme

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42
Q

Why is phosphofructokinase an allosteric enzyme?

A

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

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43
Q

What effect does ATP have on phosphofructokinase?

A

Inhibition

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44
Q

Why is the symmetrical configuration of hexose-bisphosphate useful?

A

High energy compound

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45
Q

What is mutase?

A

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

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46
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 and the generation of ATP

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47
Q

What is the fate of pyruvate under anaerobic conditions?

A

When oxygen is unavailable to be the final hydrogen accept during oxidative phosphorylation.
Pyruvate is reduced to lactate by NADH to continue substrate-level phosphorylation via glycolysis
Lactate dehydrogenase is used
Reoxidises NADH to continue glycolytic pathway

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48
Q

What enzyme is used for the reduction of pyruvate into lactate?

A

Pyruvate dehydrogenase

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49
Q

What is the benefit of pyruvate –> lactate conversion?

A

Reoxidises NADH to continue glycolytic ATP synthesis

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50
Q

What is the overall reaction for anaerobic respiration?

A

Glucose +2pi + 2ADP –> 2 Lactate + 2ATP + 2H2O

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51
Q

What is the fate of pyruvate under aerobic conditions?

A

Actively transported to mitochondrial matrix
Link reaction
Dehydrogenated and decarboxylated to an acetate
Combines with Coenzyme-A (CoA) to form acetyl CoA

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52
Q

What enzymes convert pyruvate into acetyl-CoA?

A

Pyruvate dehydrogenase and pyruvate decarboxylase

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53
Q

What is the overall equation for the link reaction?

A

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

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54
Q

What are the products of the link reaction per glucose molecule?

A

2 carbon dioxide
2 acetyl-CoA
2 NADH

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55
Q

What is the fate of pyruvate under anaerobic conditions in yeast?

A

Loses carbon dioxide –> Ethanal (Pyruvate decarboxylase)
Ethanal is reduced by NADH to ethanol
Alcoholic fermentation

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56
Q

What coenzyme assists with decarboxylation of pyruvate into ethanal?

A

Thiamine pyrophosphate

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57
Q

What is the neural response to lactate production?

A

Release of hydrogen ions enter into the blood, subsequently dropping blood pH
Detected by chemoreceptors within the carotid sinus and aortic arch
Triggers CNS to reduce muscle contraction, muscle have time to recover and return to aerobic respiration.

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58
Q

What happens to lactate in the blood plasma?

A

Transported to the liver, converted back to pyruvate

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59
Q

Where is lactate dehydrogenase predominantly located?

A

Heart, liver, kidneys, skeletal muscle, blood and lungs

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60
Q

What happens to LDH through cell necrosis?

A

Necrosis caused LDH release into circulation, hence influencing serum levels.
Diagnostic of myocardial infarctions, liver disease, muscle injury, muscular dystrophy and pulmonary infarction

61
Q

What is creatine phosphate?

A

Higher phosphoryl transfer potential than ATP.
Thereby, ATP molecules having a relatively moderate intermediate position.
Creatine phosphate reservoir within muscles, high potential phosphoryl groups, transferred to adp via creatine kinase

62
Q

Which enzyme transfers the high potential phosphoryl group to ADP?

A

Creatine kinase

63
Q

Which types of bonds exist in creatine phosphate?

A

Phosphoanhydride bonds

64
Q

What is the equation of creatine phosphate?

A

Creatine phosphate + ADP + H= –> Creatine + ATP

65
Q

What is Beri Beri?

A

Considered to be a thiamine deficient disease, damaged PNS

Weakness of musculature

66
Q

What is thiamine pyrophosphate?

A

Cofactor thiamine pyrophosphate to pyruvate dehydrogenase (PDH)
Easily deprotonated into a carbanion that attacks pyruvate

67
Q

How does thiamine pyrophosphate attack pyruvate easily?

A

Easily deprotonated into carbanion

68
Q

What is the function of thiamine pyrophosphate?

A

Assists in the decarboxylation of pyruvate

69
Q

What is the function of mitochondria?

A

Provides the site of aerobic respiration, releasing energy for the cell.
The highly folded membrane provides proteins of the ETC for ATP synthesis by oxidative phosphorylation and Krebs cycle

70
Q

What ribosomes does mitochondria possess?

A

70S

71
Q

What is the initial amino acid of mitochondrial transcripts?

A

Formylated methionine

72
Q

Where does the Krebs cycle occur?

A

The mitochondrial fluid matrix

73
Q

What is the role of the Krebs cycle?

A

Convert the acetate group to carbon dioxide and hydrogen.

Complete oxidation of glucose

74
Q

What is the initial step of the Krebs cycle?

A

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

75
Q

What is isocitrate decarboxylated to?

A

Citrate –> alpha-ketoglutarate

76
Q

What is citrate converted into?

A

isocitrate

77
Q

Describe the Krebs cycle pathway:

A

Citrate –> isocitrate –> alpha-ketoglutarate –> Succinyl-CoA –> Succinate –>Fumarate –> Malate –> oxaloacetate

78
Q

How many molecules of carbon dioxide is released by one turn of the krebs cycle?

A

2 molecules of carbon dioxide

79
Q

What are the products of the Krebs cycle?

A

2CO2, 3 NADH, 1FADH2, 1 ATP + 1GTP

80
Q

How many molecules of water required for one turn?

A

2 water molecules

81
Q

What molecule supplies phosphate groups to phosphorylate ADP to ATP?

A

Creatine phosphate

82
Q

Whats is a transamination reaction?

A

Process by which amino acids are removed and transferred to acceptor keto acids

83
Q

Which molecules arise from transamination of amino acids?

A

Pyruvate, acetyl-CoA, aceteoacetyl-CoA, alpha-ketoglutarate
Succinyl CoA
Fumarate
Oxaloacetate

84
Q

Which 3 amino acids are susceptible for phosphorylation

A

Serine, threonine, tyrosine (OH) group

85
Q

What is formed from an alanine + ketoacid?

A

Pyruvate and glutamate via aminotransferase

86
Q

Why is the glycerol phosphate shuttle used?

A

This is because the inner mitochondrial membrane is relatively impermeable to NADH and NAD+ (Glycolytic derived)
Electrons are transferred to glycerol-3-phosphate into the mitochondrial membrane

87
Q

What molecules does NADH transfer electrons to?

A

Dihydroxyacetone phosphate

88
Q

Where is glycerol-3-phosphate located?

A

Outer mitochondrial membrane

89
Q

What happens to dihydroxyacetone phosphate upon electron donation?

A

Forms glycerol-3-phosphate

90
Q

Which enzyme catalyzes the transfer of electrons?

A

Cytosolic glycerol-3-phosphate dehydrogenase

91
Q

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

A

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

92
Q

How is dihydroxyacetone phosphate reformed?

A

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

93
Q

What is subsequently formed via the glycerol-phosphate shuttle?

A

FADH2

94
Q

How does FADH2 transfer electrons?

A

Ubiquinone (COQ) & complex II reduced in the intermitochondrial membrane, transfers electrons to coenzyme Q

95
Q

Where does the malate-aspartate shuttle occur?

A

Within heart and liver cells

96
Q

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

A

Oxaloacetate

97
Q

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

A

Malate (Malate dehydrogenase catalyzes redox)

98
Q

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

A

Malate dehydrogenase

99
Q

What is the destination of malate?

A

Traverses into the inner mitochondrial membrane, and is reoxidised by NAD+ , forming NADH and Oxaloacetate

100
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

101
Q

What is the reaction of oxaloacetate and glutamate?

A

Oxaloacetate + glutamate –> Asparate + alpha-ketoglutarate

102
Q

What enzyme catalyses the transamination of oxaloacetate?

A

Aspartate-transaminase

103
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 and oxaloacetate

104
Q

What is oxidative phosphorylation?

A

Subsequent oxidation-reduction reactions in which electrons are transferred from reduced NAD/FAD by a series of electron carriers to the final hydrogen acceptor, oxygen; generating ATP through chemiosmosis.

105
Q

What is cytochrome oxidase?

A

Enzyme that recieves electrons from cytochromes and is reduced.

106
Q

What is the final hydrogen acceptor in the ETC?

A

oxygen

107
Q

How are NADH oxidised?

A

Formation of hydride ion; electron pair donation

Hydride ion dissociates into proton and 2 electrons

108
Q

Which complexes within the ETC pump hydrogen ions into the intermembrane space?

A

Complex 1, 3, and 4 are associated with proton pumps which actively pump hydrogen ions to establish an electrochemical hydrogen ion gradient

109
Q

Which complex do hydrogen ions pass through into the mitochondrial matrix?

A

Complex 5, associated with ATPase

110
Q

Which enzyme resides within complex II?

A

Complex II contains succinate dehydrogenase

111
Q

What is the role of succinate dehydrogenase?

A

Catalyses the oxidation of succinate to fumarate. Transfers electrons to FAD –> FADH2

112
Q

How is FADH2 reoxidised back into fad?

A

Electrons are transferred from FADH2 to iron sulfide proteins in complex II. The electrons are passed to Coenzyme Q and are passed to complex III

113
Q

What is the maximum number of ATP molecules produced by oxidative phosphorylation?

A

38

114
Q

Why is the number of ATP molecules produced less than the theoretical maximum?

A

ATP used to actively transport pyruvate into the mitchondrion
ATP used to shuttle electrons from reduced glycolytic NAD
Energy needed to transport ADP from cytoplasm to mitochondria
Protons leak across the outermitochondrial membrane, reduces number of protons left to generate proton motive force

115
Q

What is another name for Coenzyme Q?

A

Ubiquinone

116
Q

What is the role of coenzyme Q?

A

Associated with Complex II; transfers electrons from complex 1 –> 3, and 2 –> 3
NADH dehyrogenase complex –> cytochrome bc1

117
Q

Describe the order of electron transfer from NADH?

A

NADH dehydrogenase complex in 1 (Flavoprotein) –> Coenzyme Q –> Cytochrome bc1 –> Cytochrome C –> Cytochrome A (Complex IV) –> oxygen

118
Q

How many ATP molecules are formed per reduced FAD molecule?

A

2 ATP molecules

119
Q

What is the term used to describe the enzymes invovled in the ETC?

A

Oxidoreductases

120
Q

What is the chemiosmotic theory?

A

Hydrogen ions are actively pumped from the matrix through the inner mitochondrial membrane to the intermembrane space.
Concentration of protons increase, difference in pH, electrical potential difference occurs. Acidic conditions
Proton motive force causes hydrogen ions to diffuse along the electrochemical and concentration gradient through stalked particles into the matrix.
Energy released from hydrogen ion influx, drives the rotation of ATPase enzymes, stimulating the catalysis of ADP and inorganic phosphate ions into ATP

121
Q

What does negative standard redox potentials imply?

A

Greater reducing power, tendency to donate electrons

122
Q

What does positive standard redox potentials imply?

A

Position of equilibrium favours positive direction, thus stronger oxidising agent

123
Q

How are the electron carries arranged within the ETC?

A

In order of increasing oxidising power; energetically favourable

124
Q

What is the purpose of teflon in a clark electrode?

A

Form oxygen-permeable membrane lining the base of the chamber

125
Q

What material comprises the cathode (-) in the Clark electrode?

A

Platinum

126
Q

What material comprises the anode (+) in the Clark electrode?

A

Silver

127
Q

What potential difference is applied across the Clark electrode?

A

+60V

128
Q

What occurs at the platinum electrode?

A

Oxygen diffuses through the Teflon membrane and is reduced to water.

129
Q

What occurs at the Silver electrode?

A

Silver atoms oxidized to Ag+, four electrons are released

130
Q

What is the role of the silver electrode?

A

The released electrons are required for the reduction of oxygen into water, thus the concentration of oxygen is directly proportional to the current;

131
Q

What is the relationship between current and oxygen?

A

Direct proportionality

Greater the concentration of oxygen, the greater the flow of electrons

132
Q

What two components comprise ATP synthase?

A

Membrane bound part (F0) and a part that projects into the matrix space (F1)

133
Q

What protein subunits comprise F0?

A

a,b,c

134
Q

What protein subunits comprise f1?

A

alpha, gamma, beta

135
Q

Which subunit initially rotates in ATP-synthase, drived by hydrogen ion diffusion?

A

C subunits rotate, releasing energy that enable conformation change

136
Q

Which f1 subunit is connected to c subunit and is subsequently rotated?

A

Gamma

137
Q

How does gamma rotation synthesise ATP?

A

Behaves as an asymmetrical axel,b subunits undergo structural changes, rotation drives transition of catalytic portions of b subunits. affinities for ATP and ADP altered
Torsional energy flows from the catalytic subunit into the bound ADP, and Pi

138
Q

What type of energy drives ATP synthesis?

A

Torsional energy

139
Q

What are the mechanisms of actions of cyanide and azide?

A

Bind with high affinity to the ferric form of cytochrome oxidase, blocking final transfer of electrons to oxygen
This inhibits aerobic respiration

140
Q

What is the mechanism of action of Arsenic?

A

Inhibits action of pyruvate dehydrogenase, thus pyruvate cannot be converted into Acetyl-CoA

141
Q

What type of inhibitor is malonate?

A

Competitive inhibitor

142
Q

What is the mechanism of action of malonate?

A

Resembles succinate, acts as a competitive inhibitor of succinate dehyrogenase. Thus slows down the flow of electrons from succinate to ubiquinone by inhibiting the oxidation of succinate to fumarate

143
Q

What is End-product inhibition?

A

End product binds to early enzymes, rendering it inactive via non-competitive inhibition. Controls rate of reaction

144
Q

What is the mechanism of action of oligomycin?

A

Antibiotic produced by streptomyces, inhibits oxidative phosphorylation by binding to the stalk of ATP synthase, blocks flow of protons into matrix.
Accumulation of protons within the intermembrane space.

145
Q

Why does the inhibition of ATP synthase by oligomycin present pathology?

A

Saturation of intermembrane space with protons means that protons cannot be actively pumped, inhibits ETC electron flow

146
Q

What is the mechanism of action of DNP?

A

Shuttles protons across the inner mitochondrial membrane uncouples from oxidative phosphorylation from ATP synthesis.
Increases metabolic rate and body temperature

147
Q

What kind of molecule is DNP?

A

Proton ionophore

148
Q

What does DNP cause?

A

Non-shivering thermogenesis

149
Q

Why does non-shivering thermogensis occur?

A

Uncoupling of oxidative phosphorylation, UCP-1 (thermogenin), channel activated in response to drop in core body temperature, allows protons to bypass ATP synthase, releasing heat from dissipation of the proton gradient

POM (Principles of Medicine) (34 decks)

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