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
2
Q
What are oxidation-reduction reactions?
A
Electron transfer
3
Q
What are ligation reactions?
A
Formation of covalent bonds
4
Q
What are isomerization reactions?
A
Rearrangement of atoms to form isomers
5
Q
What are group transfer reactions?
A
Transfer of a functional group from one molecule to another
6
Q
What are hydrolytic reactions?
A
Cleavage of a bond by the addition of water
7
Q
What are the reduction reactions?
A
Addition of electrons or the addition of hydrogen
Removal of oxygen
8
Q
What are oxidation reactions?
A
Addition of oxygen/removal of hydrogen
9
Q
Name the hydrogen acceptors present within the electron transport chain:
A
Flavoprotein, coenzyme Q, cytochrome b,c,a
10
Q
What is NAD?
A
Nicotinamide adenine dinucleotide. Coenzyme hydrogen acceptor.
Oxidised form is denoted as NAD+
11
Q
What is FAD?
A
Flavin adenine dinucleotide
12
Q
What is the first step of glycolysis?
A
Glucose is phosphorylated into glucose-6-phosphate by hexokinase (Phosphoryl transfer)
13
Q
Which enzyme catalyses the initial phosphorylation of glucose?
A
Hexokinase-4
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)
15
Q
What enzyme catalyses the isomerization of glucose-6-phosphate –> Fructose-6-phosphate?
A
Phosphoglucoisomerase
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)
17
Q
How is fructose-6-phosphate phosphorylated into fructose-1,6-bisphosphate?
A
Phosphofructokinase
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)
19
Q
What molecules is fructose-1,6-bisphosphate hydrolysed into?
A
Glyceraldehyde-3-phosphate
Dihydroxyacetone phosphate
20
Q
What happens to dihydroxyacetone phosphate?
A
Undergoes isomerisation reaction into glyceraldehyde-3-phosphate via triosephosphate isomerase (TPI)
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
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
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)
24
Q
What enzyme catalyses the convention of 1,3bisphosphoglycerate into 3-phosphoglycerate?
A
Phosphoglycerate kinase
25
What is the destination of 3-phosphoglycerate?
3-Phosphoglycerate undergoes isomerization reaction into 2-phosphoglycerate by phosphoglycerate mutase
26
What enzyme isomerises 3-phosphoglycerate into 2-phosphoglycerate?
Phosphoglycerate mutase
27
What is the destination of 2-phosphoglycerate?
2-phosphoglycerate is converted into phosphoenolpyruvate by enolase (dehydration, water is removed)
28
What converts 2-phosphoglycerate into phosphoenolpyruvate?
Enolase
29
What type of reaction is the conversion of 2-phosphoglycerate into phosphoenolpyruvate?
Dehydration (water is removed)
30
What is the destination of phosphoenolpyruvate?
Phosphoenolpyruvate is converted into pyruvate by pyruvate kinase. ATP is formed
31
Where does glycolysis occur?
Cellular cytoplasm
32
What is glycolysis?
Substrate level phosphorylation of respiratory substrate glucose to synthesize pyruvate, ATP, and reduced NAD to generate ATP
33
Why is glucose phosphorylated?
Phosphorylation makes glucose more reactive, therefore unable to pass through cell membrane (negative charge)
Stored within cell
Regulated by phosphofructokinase
34
How many gross ATP molecules is produced via glycolysis?
4
2 via 1,3bisphosphoglycerate --> 3-bisphosphoglycerate
2 via phosphoenolpyruvate --> pyruvate
35
How many net ATP is produced?
2
36
What is the destination of the 2 NADH molecules under aerobic conditions?
Pass through the outer mitochondrial membrane into the electron transport chain
37
What is the destination of pyruvate under aerobic conditions?
Actively transported into the mitochondrial matrix, where it undergoes the link reaction
38
What is released from glucose phosphorylation into glucose-6-phosphate?
Proton
39
What ion is required to enable phosphorylation?
Magnesium ion
40
Why is magnesium required for the initial phosphorylation of glucose?
Positively charged ion shields negative ATP phosphate group.
41
What type of enzyme is phosphofructokinase?
Allosteric enzyme
42
Why is phosphofructokinase an allosteric enzyme?
The pace of glycolysis is dependent on enzyme activity, allosterically controlled by ATP.
ATP is an inhibitor
43
What effect does ATP have on phosphofructokinase?
Inhibition
44
Why is the symmetrical configuration of hexose-bisphosphate useful?
High energy compound
45
What is mutase?
An enzyme that catalyzes the intramolecular shift of a chemical group (phosphoryl)
46
What are the advantages of enol phosphates? (Phosphoenolpyruvate)
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
47
What is the fate of pyruvate under anaerobic conditions?
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
48
What enzyme is used for the reduction of pyruvate into lactate?
Pyruvate dehydrogenase
49
What is the benefit of pyruvate --> lactate conversion?
Reoxidises NADH to continue glycolytic ATP synthesis
50
What is the overall reaction for anaerobic respiration?
Glucose +2pi + 2ADP --> 2 Lactate + 2ATP + 2H2O
51
What is the fate of pyruvate under aerobic conditions?
Actively transported to mitochondrial matrix
Link reaction
Dehydrogenated and decarboxylated to an acetate
Combines with Coenzyme-A (CoA) to form acetyl CoA
52
What enzymes convert pyruvate into acetyl-CoA?
Pyruvate dehydrogenase and pyruvate decarboxylase
53
What is the overall equation for the link reaction?
Pyruvate + NAD + CoA --> AcetylCoA + CO2 + NADH
54
What are the products of the link reaction per glucose molecule?
2 carbon dioxide
2 acetyl-CoA
2 NADH
55
What is the fate of pyruvate under anaerobic conditions in yeast?
Loses carbon dioxide --> Ethanal (Pyruvate decarboxylase)
Ethanal is reduced by NADH to ethanol
Alcoholic fermentation
56
What coenzyme assists with decarboxylation of pyruvate into ethanal?
Thiamine pyrophosphate
57
What is the neural response to lactate production?
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.
58
What happens to lactate in the blood plasma?
Transported to the liver, converted back to pyruvate
59
Where is lactate dehydrogenase predominantly located?
Heart, liver, kidneys, skeletal muscle, blood and lungs
60
What happens to LDH through cell necrosis?
Necrosis caused LDH release into circulation, hence influencing serum levels.
Diagnostic of myocardial infarctions, liver disease, muscle injury, muscular dystrophy and pulmonary infarction
61
What is creatine phosphate?
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
Which enzyme transfers the high potential phosphoryl group to ADP?
Creatine kinase
63
Which types of bonds exist in creatine phosphate?
Phosphoanhydride bonds
64
What is the equation of creatine phosphate?
Creatine phosphate + ADP + H= --> Creatine + ATP
65
What is Beri Beri?
Considered to be a thiamine deficient disease, damaged PNS
| Weakness of musculature
66
What is thiamine pyrophosphate?
Cofactor thiamine pyrophosphate to pyruvate dehydrogenase (PDH)
Easily deprotonated into a carbanion that attacks pyruvate
67
How does thiamine pyrophosphate attack pyruvate easily?
Easily deprotonated into carbanion
68
What is the function of thiamine pyrophosphate?
Assists in the decarboxylation of pyruvate
69
What is the function of mitochondria?
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
What ribosomes does mitochondria possess?
70S
71
What is the initial amino acid of mitochondrial transcripts?
Formylated methionine
72
Where does the Krebs cycle occur?
The mitochondrial fluid matrix
73
What is the role of the Krebs cycle?
Convert the acetate group to carbon dioxide and hydrogen.
| Complete oxidation of glucose
74
What is the initial step of the Krebs cycle?
Coenzyme A transfers the 2-carbon acetate to a 4 carbon compound (oxaloacetate) to form citrate
75
What is isocitrate decarboxylated to?
Citrate --> alpha-ketoglutarate
76
What is citrate converted into?
isocitrate
77
Describe the Krebs cycle pathway:
Citrate --> isocitrate --> alpha-ketoglutarate --> Succinyl-CoA --> Succinate -->Fumarate --> Malate --> oxaloacetate
78
How many molecules of carbon dioxide is released by one turn of the krebs cycle?
2 molecules of carbon dioxide
79
What are the products of the Krebs cycle?
2CO2, 3 NADH, 1FADH2, 1 ATP + 1GTP
80
How many molecules of water required for one turn?
2 water molecules
81
What molecule supplies phosphate groups to phosphorylate ADP to ATP?
Creatine phosphate
82
Whats is a transamination reaction?
Process by which amino acids are removed and transferred to acceptor keto acids
83
Which molecules arise from transamination of amino acids?
Pyruvate, acetyl-CoA, aceteoacetyl-CoA, alpha-ketoglutarate
Succinyl CoA
Fumarate
Oxaloacetate
84
Which 3 amino acids are susceptible for phosphorylation
Serine, threonine, tyrosine (OH) group
85
What is formed from an alanine + ketoacid?
Pyruvate and glutamate via aminotransferase
86
Why is the glycerol phosphate shuttle used?
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
What molecules does NADH transfer electrons to?
Dihydroxyacetone phosphate
88
Where is glycerol-3-phosphate located?
Outer mitochondrial membrane
89
What happens to dihydroxyacetone phosphate upon electron donation?
Forms glycerol-3-phosphate
90
Which enzyme catalyzes the transfer of electrons?
Cytosolic glycerol-3-phosphate dehydrogenase
91
What is the destination of glycerol-3-phosphate within the inner mitochondrial membrane?
The electron pair is donated from glycerol-3-phosphate to FAD prophetic group of the mitochondrial glycerol dehydrogenase to produce dihydroxyacetone phosphate
92
How is dihydroxyacetone phosphate reformed?
Oxidation of glycerol-3-phosphate diffuses back into the cytosol to continue the shuttling process
93
What is subsequently formed via the glycerol-phosphate shuttle?
FADH2
94
How does FADH2 transfer electrons?
Ubiquinone (COQ) & complex II reduced in the intermitochondrial membrane, transfers electrons to coenzyme Q
95
Where does the malate-aspartate shuttle occur?
Within heart and liver cells
96
What molecules does NADH transfer electrons to in the malate-aspartate shuttle?
Oxaloacetate
97
What molecule is oxaloacetate converted into upon reduction via NADH (Malate-aspartate shuttle)?
Malate (Malate dehydrogenase catalyzes redox)
98
What enzyme catalyzes the reduction of oxaloacetate in the malate-aspartate shuttle?
Malate dehydrogenase
99
What is the destination of malate?
Traverses into the inner mitochondrial membrane, and is reoxidised by NAD+ , forming NADH and Oxaloacetate
100
How is the formed oxaloacetate be transported across the inner mitochondrial membrane to cytosol?
Oxaloacetate transaminated into aspartate and alpha ketoglutarate via glutamate
101
What is the reaction of oxaloacetate and glutamate?
Oxaloacetate + glutamate --> Asparate + alpha-ketoglutarate
102
What enzyme catalyses the transamination of oxaloacetate?
Aspartate-transaminase
103
What is the fate of aspartate in the malate-aspartate shuttle?
Passes through the inner mitochondrial membrane into the cytosol, reacts with ketoacid to form glutamate and oxaloacetate
104
What is oxidative phosphorylation?
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
What is cytochrome oxidase?
Enzyme that recieves electrons from cytochromes and is reduced.
106
What is the final hydrogen acceptor in the ETC?
oxygen
107
How are NADH oxidised?
Formation of hydride ion; electron pair donation
| Hydride ion dissociates into proton and 2 electrons
108
Which complexes within the ETC pump hydrogen ions into the intermembrane space?
Complex 1, 3, and 4 are associated with proton pumps which actively pump hydrogen ions to establish an electrochemical hydrogen ion gradient
109
Which complex do hydrogen ions pass through into the mitochondrial matrix?
Complex 5, associated with ATPase
110
Which enzyme resides within complex II?
Complex II contains succinate dehydrogenase
111
What is the role of succinate dehydrogenase?
Catalyses the oxidation of succinate to fumarate. Transfers electrons to FAD --> FADH2
112
How is FADH2 reoxidised back into fad?
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
What is the maximum number of ATP molecules produced by oxidative phosphorylation?
38
114
Why is the number of ATP molecules produced less than the theoretical maximum?
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
What is another name for Coenzyme Q?
Ubiquinone
116
What is the role of coenzyme Q?
Associated with Complex II; transfers electrons from complex 1 --> 3, and 2 --> 3
NADH dehyrogenase complex --> cytochrome bc1
117
Describe the order of electron transfer from NADH?
NADH dehydrogenase complex in 1 (Flavoprotein) --> Coenzyme Q --> Cytochrome bc1 --> Cytochrome C --> Cytochrome A (Complex IV) --> oxygen
118
How many ATP molecules are formed per reduced FAD molecule?
2 ATP molecules
119
What is the term used to describe the enzymes invovled in the ETC?
Oxidoreductases
120
What is the chemiosmotic theory?
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
What does negative standard redox potentials imply?
Greater reducing power, tendency to donate electrons
122
What does positive standard redox potentials imply?
Position of equilibrium favours positive direction, thus stronger oxidising agent
123
How are the electron carries arranged within the ETC?
In order of increasing oxidising power; energetically favourable
124
What is the purpose of teflon in a clark electrode?
Form oxygen-permeable membrane lining the base of the chamber
125
What material comprises the cathode (-) in the Clark electrode?
Platinum
126
What material comprises the anode (+) in the Clark electrode?
Silver
127
What potential difference is applied across the Clark electrode?
+60V
128
What occurs at the platinum electrode?
Oxygen diffuses through the Teflon membrane and is reduced to water.
129
What occurs at the Silver electrode?
Silver atoms oxidized to Ag+, four electrons are released
130
What is the role of the silver electrode?
The released electrons are required for the reduction of oxygen into water, thus the concentration of oxygen is directly proportional to the current;
131
What is the relationship between current and oxygen?
Direct proportionality
| Greater the concentration of oxygen, the greater the flow of electrons
132
What two components comprise ATP synthase?
Membrane bound part (F0) and a part that projects into the matrix space (F1)
133
What protein subunits comprise F0?
a,b,c
134
What protein subunits comprise f1?
alpha, gamma, beta
135
Which subunit initially rotates in ATP-synthase, drived by hydrogen ion diffusion?
C subunits rotate, releasing energy that enable conformation change
136
Which f1 subunit is connected to c subunit and is subsequently rotated?
Gamma
137
How does gamma rotation synthesise ATP?
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
What type of energy drives ATP synthesis?
Torsional energy
139
What are the mechanisms of actions of cyanide and azide?
Bind with high affinity to the ferric form of cytochrome oxidase, blocking final transfer of electrons to oxygen
This inhibits aerobic respiration
140
What is the mechanism of action of Arsenic?
Inhibits action of pyruvate dehydrogenase, thus pyruvate cannot be converted into Acetyl-CoA
141
What type of inhibitor is malonate?
Competitive inhibitor
142
What is the mechanism of action of malonate?
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
What is End-product inhibition?
End product binds to early enzymes, rendering it inactive via non-competitive inhibition. Controls rate of reaction
144
What is the mechanism of action of oligomycin?
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
Why does the inhibition of ATP synthase by oligomycin present pathology?
Saturation of intermembrane space with protons means that protons cannot be actively pumped, inhibits ETC electron flow
146
What is the mechanism of action of DNP?
Shuttles protons across the inner mitochondrial membrane uncouples from oxidative phosphorylation from ATP synthesis.
Increases metabolic rate and body temperature
147
What kind of molecule is DNP?
Proton ionophore
148
What does DNP cause?
Non-shivering thermogenesis
149
Why does non-shivering thermogensis occur?
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
