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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
Glycolysis STEP 5
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
26
Which enzyme catalyses the isomerisation of Dihydroxyacetone to glyceraldehyde-3-phosphate?
triose phosphate isomerase
27
Glycolysis STEP 6
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
28
Which enzyme catalyses the oxidation & phosphorylation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate?
glyceraldehyde-3-phosphate dehydrogenase
29
Glycolysis STEP 7
1,3-bisphosphoglycerate turned into 3-phosphoglycerate enzyme: PHOSPHOGLYCERATE KINASE - ADP --> ATP GROUP TRANSFER
30
Which enzyme catalyses the conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate?
phosphoglycerate kinase
31
Glycolysis STEP 8
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
32
Which enzyme catalyses the isomerisation of 3-phosphpoglycerate to 2-phosphoglycerate?
phosphoglycerate mutase
33
Glycolysis STEP 9
2-phosphoglycerate is converted to phosphoenolpyruvate + H2O enzyme: ENOLASE -dehydration reaction (removes H and OH) GROUP REMOVAL
34
Which enzyme catalyses the conversion of 2-phosphoglycerate into phosphoenolpyruvate?
enolase
35
Glycolysis STEP 10
Phosphoenolpyruvate is turned into pyruvate enzyme: PYRUVATE KINASE - ADP --> ATP GROUP TRANSFER
36
Which enzyme catalyses the conversion of phosphoenolpyruvate into pyruvate?
pyruvate kinase
37
The net result of glycolysis?
1. net gain of 2 ATP | 2. 2 NADH
38
where does glycolysis take place?
Cellular cytoplasm
39
How many ATP molecules are produced during glycolysis?
4 2 via 1,3-bisphosphoglycerate 2 via phosphoenolpyruvate
40
Destination of NADH (aerobic conditions)
pass through outer mitochondrial membrane into the ETC
41
Destination of pyruvate? (aerobic conditions)
Actively transported into the mitochondrial matrix, where it undergoes the link reaction
42
What ion is required to enable phosphorylation?
Magnesium Ion
43
Why is mg required for the initial phosphorylation of glucose?
(+)vely charged ion shields negative ATP phosphate group
44
What type of enzyme is phosphofructokinase?
Allosteric enzyme | pace of glycolysis is dependent on enzyme activity, allosterically controlled by ATP ATP is an inhibitor
45
Why is symmetrical configuration of hexose-bisphosphate useful?
High E compound
46
What is mutase?
An enzyme that catalyses the intramolecular shift of a chemical group (phosphoryl)
47
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 & the generation of ATP
48
What is the fate of pyruvate under anaerobic conditions?
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
Which enzyme catalyses the conversion of pyruvate to lactate?
lactate dehydrogenase
50
What is the benefit of pyruvate --> lactate conversion
Reoxidises NADH to continue glycolytic ATP synthesis Lactate is transported to the liver, converted back to pyruvate
51
Overall reaction for anaerobic respiration
Glucose +2 Pi +2 ADP--> 2 Lactate + 2 ATP + 2 H20
52
Fate of pyruvate under aerobic conditions?
AT to mitochondrial matrix Link Reaction Dehydrogenated & decarboxylated to an acetate Combines with Coenzyme-A (CoA) to form acetyl CoA
53
What is the fate of pyruvate? (except anaerobic respiration) yeast
1. Pyruvate converted to acetaldehyde enzyme: PYRUVATE DECARBOXYLASE - H+ --> CO2 DECARBOXYLATION 2. Acetaldehyde reduced to ethanol enzyme: ALCOHOL DEHYDROGENASE - NADH + H+ --> NAD+ REDUCTION
54
What is Creatine phosphate?
- acts as a source or buffer for ATP production - doubles the time by which the cell is independent of respiration - bonds: phosphoanhydride bonds
55
creatine phosphate reaction
Creatine phosphate is converted to creatine + ATP enzyme: CREATINE KINASE - ADP + H+ --> ATP very thermodynamically favourable
56
Acetyl CoA generation | in the mitochondria
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
Structure of Acetyl CoA
thioester bond is a high-energy linkage-- readily hydrolysed, enabling acetyl CoA to donate the acetate (2C) to other molecules
58
Pyruvate dehydrogenase complex consists of ..?
pyruvate dehydrogenase & pyruvate decarboxylase
59
Overall equation for the link reaction?
Pyruvate + NAD +CoA ---> AcetylCoA + CO2 +NADH
60
Products of the Link reaction per glucose molecule
2 CO2 2 acetyl-CoA 2 NADH
61
What is Beri Beri?
Thiamine deficient disease, damaged PNS | Weakness of musculature
62
What is thiamine pyrophosphate?
Cofactor to the pyruvate dehydrogenase (PHD) | Easily deprotonated into a carbanion attacks pyruvate
63
What is the function of thiamine pyrophosphate?
Assists in the decarboxylation of pyruvate
64
Where does the Krebs cycle occur?
The mitochondrial fluid matrix
65
Role of the role of the krebs cycle?
convert the acetate group to CO2 & H | complete oxidation of glucose
66
Krebs Cycle STEP 1 | ocxaloacetate-->
Coenzyme A transfers the 2-carbon acetate to a 4 carbon compound (OXALOACETATE) to form citrate
67
Krebs Cycle STEP 2 | citrate-->
citrate --> isocitrate(6C)
68
Krebs Cycle STEP 3 | isocitrate-->
citrate --> alpha-ketoglutarate (5C) - NAD+ --> NADH waste: CO2
69
Krebs Cycle STEP 4 | a-ketoglutarate-->
a-ketoglutarate--> succinyl-CoA (4C) - NAD+ --> NADH waste: CO2
70
Krebs Cycle STEP 5 | succinyl-CoA-->
Succinyl-CoA --> succinate (4C) GTP released
71
Krebs Cycle STEP 6 | succinate-->
succinate--> fumerate(4C) -FAD --> FADH2
72
Krebs Cycle STEP 7 | fumerate-->
fumerate --> malate (4C)
73
Krebs Cycle STEP 8 | malate-->
malate --> oxaloacetate (4C) -NAD+ --> NADH
74
Describe the krebs cycle pathway:
citrate --> isocitrate --> alpha-ketoglutarate --> succinyl-CoA --> succinate --> fumarate --> malate --> oxaloacetate
75
How many molecules of CO2 is released by one turn of the Krebs Cycle?
2 molecules
76
What are the products of the krebs cycle?
``` 2 CO2 3 NADH 1 FADH2 1 ATP 1 GTP ```
77
How many molecules of H2O required for one turn?
2
78
What is a transamination reaction?
process by which amino acids are removed & transferred to acceptor keto acids
79
Which molecules arise from the transamination of a.a.?(7)
``` Pyruvate acetyl-CoA acetoacetyl-CoA alpha-ketoglutarate succinyl CoA fumarate oxaloacetate ```
80
Tricarboxylic acid cycle (TCA) waste products?
amino group is removed(excreted as urea) | carbon skeleton is funnelled into the production of glucose or Krebs Cycle
81
Which 3 a.a. are susceptible for phosphorylation?
Serine threonine tyrosin (OH) group
82
What is formed from an alanine + ketoacid?
Pyruvate & glutamate enzyme: TRANSAMINASE - switching amino group from one molecule to another GROUP TRANSFER
83
Why is the glycerol phosphate shuttle used?
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
What molecules does NADH transfer electrons to? | in glycerol phosphate shuttle
Dihydroxyacetone phosphate
85
Where is glycerol-3-phosphate located?
outer mitochondrial membrane
86
What happens to dihydroxyacetone phosphate upon electron donation?
Forms glycerol-3-phosphate
87
Which enzyme catalyses the transfer of e-?
Cytosolic glycerol-3-phosphate dehydrogenase
88
What is the destination of glycerol-3-phosphate within the inner mitochondrial membrane?
The e- pair is donated from glycerol-3-phosphate to FAD prophetic group of the mitochondrial glycerol dehydrogenase to produce dihydroxyacetone phosphate
89
How is dihydroxyacetone phosphate reformed?
Oxidation of glycerol-3-phosphate diffuses back into the cytosol to continue the shuttling process
90
What is subsequently formed via the glycerol phosphate shuttle?
FADH2
91
Where does the malate-aspartate shuttle occur?
within the heart and liver cells
92
What molecules does NADH transfer electrons to in the malate-aspartate shuttle?
oxaloacetate
93
What molecule is oxaloacetate converted into upon reduction via NADH ( malate-aspartate shuttle)?
Malate (Malate dehydrogenase catalyzes redox)
94
What enzyme catalyzes the reduction of oxaloacetate in the malate-aspartate shuttle?
Malate dehydrogenase
95
What is the destination of malate?
Transverses into the inner mitochondrial membrane, and is reoxidised by NAD+ forming NADH & oxaloacetate
96
How is the formed oxaloacetate be transported across the inner mitochondrial membrane to cytosol?
oxaloacetate transaminated into aspartate and alpha ketoglutarate via glutamate
97
Reaction of oxaloacetate & glutamate?
oxaloacetate + glutamate --> aspartate + alpha-ketoglutarate enzyme: ASPARTATE-TRANSAMINASE
98
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 & oxaloacetate
99
How many ATP molecules are produced by the reoxidation of one NADH?
3
100
How many ATP molecules are produced by the reoxidation of one FADH2?
2
101
Total ATP produced from the krebs Cycle?
3 x 3 + 1 x 2 + 1 = 12 ATP
102
What does a kinase enzyme catalyse?
Transfer a phosphate group to a substrate
103
What is substrate level phosphorylation?
Direct transfer of a high-energy phosphate group to ADP
104
What is lactate dehydrogenase? (LDH)
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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