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PoM > MBC - Cell Metabolism > Flashcards

MBC - Cell Metabolism Flashcards

1
Q

What are the 3 main steps of cellular metabolism?

A

Glycolysis, TCA cycle, oxidative phosphorylation

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2
Q

What is glycolysis

A

The oxidation of glucose in the cytosol of a cell, to produce pyruvate from the reduction of cofactors (NAD+ —> NADH), to generate some ATP.

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3
Q

What is the TCA cycle?

A

The further oxidation of small molecules in the mitochondria, including pyruvate as well as the products from the breakdown of fats and proteins. This generates ATP, as well as some waste products and reduced cofactors NADH and FADH2

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4
Q

What is oxidative phosphorylation?

A

This is the re-oxidisation of the reduced cofactors in the mitochondria, and is when the bulk of cellular ATP is generated.

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5
Q

How do proteins contribute to the TCA cycle?

A

Amino acids can be broken down into 7 products which can all enter the TCA cycle, either glycogenic amino acids or ketogenic amino acids.

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6
Q

How do fats contribute to the TCA cycle?

A

Fatty acids and glycerol all contribute to acetyl CoA which then enters the TCA cycle.

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7
Q

What is Delta G for the combustion of glucose?

A

-2872 kJ/mol

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8
Q

What is Delta G for the metabolism of glucose and why?

A

-1178 kJ/mol This is because we generate between 36-38 molecules of ATP with the metabolism of glucose, each with a free energy of -31kJ/mol. This means that at maximum, we generate -1178kJ/mol.

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9
Q

How efficient is glucose metabolism

A

41%

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10
Q

What are the 6 main types of metabolic reaction?

A

Oxidation/reduction Ligation requiring the cleavage of ATP Isomerisation Group transfer Addition or removal of functional groups Hydrolytic

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11
Q

How many reactions are in glycolysis?

A
  1. Half of these are energy consuming reactions whereas the other half are regaining ATP (energy). We overall invest 2ATP but we get back 4ATP as well as 2NADH which can be oxidised later for ATP generation
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12
Q

What is the first step of glycolysis?

A

Glucose is converted to glucose-6-phosphate via hexokinase. This is an irreversible group transfer reaction. This reaction involves a hydrolysis of an ATP molecule into ADP.

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13
Q

What is the second step in glycolysis?

A

G-6-P is converted to fructose-6-phosphate via phosphoglucose isomerase. This is an isomerisation reaction

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14
Q

What is the third step in glycolysis?

A

Fructose-6-phosphate is converted to fructose-1,6-biphosphate via phosphofructokinase. Phosphofructokinase levels dictate how much sugar can enter there glycolysis pathway. An ATP is also used in this reaction, which is a group transfer reaction

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15
Q

What is the fourth step in glycolysis?

A

F-1,6-P is broken down into two high energy phosphate containing molecules: Dihydroxyacetone phosphate and Glyceraldehyde-3-phosphate via aldolase. This is a hydrolytic reaction.

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16
Q

What is the fifth step in glycolysis?

A

DHAP is converted to another GA-3P via the enzyme triode phosphate isomerase (TPI) this is an isomerisation reaction.

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17
Q

Is TPI essential?

A

Yes - a deficiency of TPI is the only known fatal glycolytic enzymopathy, with most sufferers dying within 6 years.

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18
Q

What is the sixth step of glycolysis?

A

Glyceraldehyde-3-phosphate is converted to 1,3-bisphosphoglycerate via G-3-P dehydrogenase and the presence of NAD+ and Pi. This is therefore both a redox reaction and a group transfer

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19
Q

What is the 7th step of glycolysis?

A

1,3-bisphosphoglycerate is converted to 3-phosphoglycerate via phosphoglycerate kinase, generating ATP in this group transfer reaction

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20
Q

What is the 8th step of glycolysis?

A

3-phosphoglycerate is converted to 2-phosphoglycerate via phosphoglycerate mutase - isomerisation reaction

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21
Q

What is the 9th step of glycolysis?

A

2-phosphoglycerate is converted to phosphoenolpyruvate and water via enolase. This is therefore both a functional group removal and a dehydration reaction.

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22
Q

What is the final (10th) step of glycolysis?

A

Phosphoenolpyruvate is converted to pyruvate via pyruvate kinase and ADP+Pi, generating ATP as well

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23
Q

What are the 3 fates fo pyruvate?

A
  1. Alcoholic fermentation into ethanol 2. Dehydrogenation to lactate 3. Oxidation to form Acetyl CoA for the TCA cycle
24
Q

What happens in the conversion of pyruvate to ethanol?

A

Pyruvate is converted to acetaldehyde via pyruvate decarboxylase, using H+ and producing CO2 as a byproduct. Acetaldehyde is then converted to ethanol via alcohol dehydrogenase and using an NADH which is oxidised to NAD+

25
Q

Why is alcoholic fermentation and dehydrogenation to lactate important?

A

They both allow for the regeneration of NAD+ which is essential for conditions of oxygen deprivation. In these conditions, the rate of NADH formation is greater than the rate of NAD+ formation (oxidation), therefore it is crucial that these reactions occur, as NAD+ is need for any ATP production.

26
Q

How does pyruvate become lactate?

A

Pyruvate is reduced to lactate via lactate dehydrogenase along with the oxidation of NADH to NAD+, thus creating a redox reaction

27
Q

How does pyruvate become Acetyl CoA?

A

Pyruvate + HS-CoA —-> Acetyl CoA + CO2 (under the reduction of NAD+ to NADH) via pyruvate dehydrogenase

28
Q

What allows Acetyl CoA to be useful in the TCA cycle?

A

It has a thioester linkage which is high energy thus readily hydrolysed. This means that the acetate (2C) is easily added into the TCA cycle.

29
Q

What is Beri-Beri?

A

This is a deficiency in thiamine (derivative of vitamin B1), and is a constituent of thiamine pyrophosphate. Thiamine pyrophosphate is a cofactor of pyruvate dehydrogenase, therefore a thiamine deficiency consequently leads to lack of Acetyl-CoA and thus the metabolic defects of Beri Beri

30
Q

What are the symptoms of Beri-Beri?

A

Decreased musculature, decreased cardiac output, peripheral nerve damage, brain damage (because the brain relies almost entirely on glucose metabolism).

31
Q

What is the net gain of one turn in the TCA cycle?

A

3 NADH 1 FADH2 2 CO2 1 GTP (or ATP equivalent)

32
Q

What is the first step of the TCA cycle?

A

Acetate of Acetyl CoA is joined to oxaloacetate via citrate synthase to form 6C citrate.

33
Q

What is 2nd step of TCA

A

Citrate is isomerised to isocitrate via aconitase

34
Q

What is 3rd step of TCA

A

Isocitrate is oxidised to 5C a-ketoglutarate with the reduction of NAD+ to NADH and the loss of CO2, via isocitrate dehydrogenase

35
Q

What is 4th step of TCA

A

a-ketoglutarate is oxidised to succinyl-CoA via a-ketoglutarate dehydrogenase, and the reduction of NAD+, removal of CO2 and the addition of CoA.

36
Q

What is 5th step of TCA

A

Succinyl-CoA undergoes group transfer: CoA is replaced by phosphate group which is then used to add to GDP or ADP to make GTP or ATP respectively, and succinate as the main product, via succinly-CoA synthetase

37
Q

What is 6th step of TCA

A

Succinate is oxidised to fumarate, along with the reduction of FAD, via succinate dehydrogenase

38
Q

What is 7th step of TCA

A

Fumarate is converted to malate due to the addition of water, via fumarase

39
Q

What is 8th step of TCA

A

Malate ix oxidised to oxaloacetate via malate dehydrogenase, and NAD+ is reduced.

40
Q

What kind of reactions are involved in protein metabolism ?

A

Transamination reactions: amine group transferred from one amino acid to one keto acid to form a new pair of amino and keto acid

41
Q

Can amino acids enter TCA cycle?

A

Yes - degradation of all 20 amino acids leads to 7 products which can all enter the TCA cycle

42
Q

What are the 7 products that comes from amino acid degradation?

A

Acetyl CoA Acetoacetyl CoA Fumarate A-ketoglutarate Succinyl CoA Malate Oxaloacetate

43
Q

How are the amino acids degraded?

A

The amino group is removed and eventually excreted out as urea, whilst the carbon skeleton is either funnelled into glucose production or the TCA cycle.

44
Q

What is an example of transamination?

A

Alanine (amino) and a-ketogluatarate (keto) undergo transamination via alanine aminotransferase. This produces pyruvate and glutamate (gluatamate is reconverted to a-ketoglutarate via glutamate dehydrogenase)

45
Q

How do we transfer NADH form the cytosol to the mitochondrial matrix for oxidative phosphorylation

A

Glycerol-phosphate shuttle - used in skeletal muscle and brain Malate-aspartate shuttle - liver, heart and kidneys

46
Q

Explain the glycerol-phosphate shuttle step 1

A

Dihyrodxyacetone phosphate takes the 2 electrons (2H) from NADH, to form Glycerol-3-phosphate via glycerol-3-phosphate dehydrogenase.

47
Q

Explain the glycerol-phosphate shuttle step 2

A

Glycerol-3-phosphate is then converted back to DHAP via mitochondrial glycerol-3-phosphate dehydrogenase, however the 2H are transferred to FAD to become FADH2

48
Q

Explain the glycerol-phosphate shuttle step 3

A

FADH2 then transfers its 2H to co-enzyme Q to become Q2, this co-enzyme is part of the ETC in the mitochondrial matrix.

49
Q

Explain malate aspartate shuttle step 1

A

Aspartate and a-ketoglutarate undergo a transamination reaction in the cytosol via aspartate transaminase, forming oxaloacetate and glutamate.

50
Q

Explain malate aspartate shuttle step 2

A

Oxaloacetate then undergoes reduction to malate, via malate dehydrogenase whilst NADH is oxidised and transfers its 2H to form malate.

51
Q

Explain malate aspartate shuttle step 3

A

Malate then enters the matrix and is oxidised to form oxaloacetate, via malate dehydrogenase, along with the formation of NADH inside the mitchondria.

52
Q

Explain malate aspartate shuttle step 4

A

Oxaloacetate is then reconverted back to apsartate through another transamination reaction with glutamate, also forming a-ketoglutarate with aspartate in the matrix.

53
Q

What reactions are occurring in the malate aspartate shuttle?

A

Redox reactions and transamination reactions.

54
Q

Explain the Warburg effect in cancerous cells

A

It was noticed that some cancerous cells were enhancing aerobic glycolysis however then producing lactate despite having a plentiful supply of oxygen.

55
Q

What enzymes are affected in the Warburg effect?

A

Isocitrate dehydrogenase Fumerase Succinate dehydrogenase All of these enzymes had reduced activity, therefore there TCA cycle was suppressed and lactate production ensued.

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