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Y1 - PoM - Week 1 > Cellular Metabolism 1 - Polysaccharides + Amino Acids > Flashcards

Cellular Metabolism 1 - Polysaccharides + Amino Acids Flashcards

+ Carbohydrates and amino acids

1
Q

Catabolic Reactions?

A

Bond breaking

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2
Q

Anabolic Reactions?

A

Bond making (synthesising components)

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3
Q

3 Main Stages of Cellular Metabolism:

A
  1. Glycolysis - occurs in the cytosol, oxidation of glucose and reduction of NAD to generate ATP.
  2. TCA (TriCarboxylic Acid) cycle, occurs in the mitochondria.
  3. Oxidative Phosphorylation - occurs in the mitochondria, previously reduced co-factors from 1. and 2. are re-oxidised.
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4
Q

Which stage produces most ATP?

A

Oxidative Phosphorylation

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5
Q

What are the waste products from Cellular Metabolism?

A

H2O (from reduction of oxygen) and urea (from breakdown of amino acids)

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6
Q

∆G° for cellular oxidation of glucose = ?

A

-2872 kJ/ mol

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7
Q

∆G° for breaking of phosphoanhydride bond?

A

-31 kJ/ mol

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8
Q

How many molecules of ATP is generated for complete oxidation of glucose?

A

36-38

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9
Q

What does ∆G° have to be for the reaction to be feasible?

A

Negative

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10
Q

How is the Ea overcome in the reactions?

A

Enzymes and body temperature (heat)

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11
Q

Efficiency of this process?

A

41%

(-31 x 38) / -2872 = 0.41

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12
Q

What are the 6 types of reactions?

A
  1. Redox = electron transfer
  2. Ligation requiring ATP cleavage = covalent bond formation
  3. Isomerisation = rearrangement of atoms to form isomers
  4. Group Transfer = transfer functional group from one molecule to another
  5. Hydrolytic = Bond breaking by addition of H2O
  6. Addition or removal of functional groups = usually involves C=C double bond
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13
Q

Isomerase is responsible for…?

A

Isomerisation

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14
Q

Kinase is responsible for…?

A

Catalysing the transfer of phosphate groups from one molecule to another (group transfer)

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15
Q

Dehydrogenase is responsible for …?

A

Redox reactions

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16
Q

2 main stages of glycolysis?

A
  1. Form a high energy compound (invest ATP)

2. Split a high energy compound (generate ATP)

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17
Q

How many reactions in glycolysis?

A

10 small reactions (With small Eas)

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18
Q

Stage 1:
Equation
Type of Reaction

A

Glucose —-hexokinase—> glucose-6-phosphate + H+

Requires ATP, which adds a phosphate to the glucose (essentially irreversible commiting cell to glycolysis), forming ADP
Group transfer

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19
Q

Stage 2:
Equation
Type of Reaction

A

Glucose-6-phosphate —-phosphoglucose isomerase—> fructose-6-phosphate
Isomerisation

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20
Q

Stage 3:
Equation
Type of Reaction

A

fructose-6-phosphate —-phosphofructokinase—-> fructose-1,6-biphosphate

Requires ATP to form ADP
Group Transfer

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21
Q

Why are stages 2 and 3 important?

A

To try and make the molecule symmetrical

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22
Q

Stage 4:
Equation
Type of Reaction

A

fructose-1,6-biphosphate —-aldolase—-> glyceraldehyde-3-phosphate + dihydroxyacetone phosphate

2 high energy compounds produced
Hydrolytic

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23
Q

Stage 5:
Equation
Type of Reaction

A

dihydroxyacetone phosphate —-triose phosphate isomerase—-> glyceraldehyde 3-phosphate

End up with 2x glyceraldehyde 3-phosphate (one from stage 4)
Isomerisation

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24
Q

Stage 6:
Equation
Type of Reaction

A

This reaction occurs 2x:
glyceraldehyde 3-phosphate —-glyceraldehyde 3-phosphate dehydrogenase—-> 1,3-biphosphoglycerate

Requires NAD+ and Pi to form NADH (per reaction)
Redox and group transfer (dehydrogenation?)

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25
Q

Stage 7:
Equation
Type of Reaction

A

This reaction occurs 2x:
1,3-biphosphoglycerate —-phosphoglycerate kinase—-> 3-phosphoglycerate

Requires an ADP which accepts a Pi to form ATP (per reaction)
Group transfer

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26
Q

Stage 8:
Equation
Type of Reaction

A

This reaction occurs 2x:
3-phosphoglycerate —-phosphoglycerate mutase—-> 2-phosphoglycerate

Isomerisation

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27
Q

Stage 9:
Equation
Type of Reaction

A

This reaction occurs 2x:
2-phosphoglycerate —-enolase dehydration—-> phosphoenolpyruvate + H2O

Group removal

28
Q

Stage 10:
Equation
Type of Reaction

A

This reaction occurs 2x:
phosphoenolpyruvate —-pyruvate kinase—-> pyruvate

Requires an ADP to form ATP (per reaction)
Group Transfer

29
Q

Net result of glycolysis:

A

Uses 2ATP, produces 4ATP and 2NADH

Therefore 2ATP + 2NADH

30
Q

What are the 3 fates of pyruvate?

A
  1. Alcohol Fermentation
  2. Lactate Production
  3. Acetyl CoA production
31
Q

Why is pyruvate converted into another molecule (3 fates)?

A

NAD+ replenishment for the continuation of glycolysis

32
Q

Alcohol Fermentation:
Equation
Type of Reaction

A

2 steps:
pyruvate —-pyruvate decarboxylase—-> acetaldehyde
Requires a H+ ion and releases a CO2 molecule

acetaldehyde —-alcohol dehydrogenase—-> ethanol
Requires NADH and H+ to form NAD+ and H2

Decarboxylation and dehydrogenation

33
Q

Where does alcohol fermentation take place?

A

Anaerobic respiration in yeasts

34
Q

Lactate Production:
Equation
Type of Reaction

A

pyruvate —-lactate dehydrogenase—-> lactate
Requires NADH and H+ to form NAD+ and H2

Redox

35
Q

Where does lactate production take place, and why?

A

Anaerobic respiration in mammalians, because in order for glycolysis to continue, NAD+ must be replenished

36
Q

What happens to the lactate afterwards?

A

Most of it is transported back to the liver, which has a large number of NAD+/NADH to covert the lactate back to pyruvate for other metabolic pathways

37
Q

What can LDH (lactate dehydrogenase) and creatine kinase be used as a diagnostic tool for?

A

Strokes, heart attacks, muscle injuries

38
Q

Why can LDH and creatine kinase be used as a diagnostic tool?

A

Normally, these are present within cells. When a cell dies or is damaged, they are released into the circulation, so serum levels of LDH are elevated

39
Q

AcetylCoA production (Link Reaction)
Equation
Type of Reaction

A

Pyruvate + HS-CoA —-pyruvate dehydrogenase complex—-> AcetylCoA + CO2
Requires NAD+ and releases NADH

Decarboxylation and redox?

40
Q

Where does the Link Reaction occur?

A

In the mitochondria

41
Q

Why can Acetyl CoA readily donate acetate to other molecules?

A

The thioester bond is a high energy linkage that can be readily hydrolysed

42
Q

PDH complex stands for?

A

Pyruvate dehydrogenase

43
Q

PDH is made up of?

A

3 enzymes and 5 co-factor enzymes, including thiamine pyrophosphate (a co-factor)

Lipoamide Reductase Transacetylase (Lipoamide)
Dihydrolipoyl Dehydrogenase (FAD)
Pyruvate Decarboxylase (Thiamine Pyrophosphate)
Other co-factors: NAD+ and CoA

44
Q

Why is thiamine pyrophosphate useful in the PDH complex?

A

It readily loses a proton, and the resulting carbanion attacks pyruvate

45
Q

Where is thiamine derived from?

A

Vitamin B1

46
Q

What does deficiency of Vitamin B1/ thiamine cause?

Symptoms and which organ is more vulnerable?

A

Beri-beri, symptoms include damage to PNS (peripheral nervous system), weakness of musculature, and decreased cardiac output.
The brain - relies on glucose metabolism

47
Q

Creatine Phosphate as a Buffer:

Equation

A

creatine phosphate —-creatine kinase—-> creatine + ATP

Requires ADP + H+ to form the ATP

48
Q

Why is creatine phosphate useful in muscles?

A

Buffers demands for phosphates, i.e is readily able to supply phosphates to ADP to form ATP for muscle contraction (substrate level phosphorylation)

49
Q

Where does the Krebs/TCA cycle take place?

A

Mitochondrial Matrix

50
Q

First step of TCA?

A

2C molecule from Acetyl CoA joins with oxaloacetate (4C molecule) to form citrate (6C molecule)

51
Q

What processes does the citrate undergo?

A

2 decarboxylations, several redox reactions to generate several reduced co-factors

52
Q

Net products of TCA per glucose

A

10 NADH, 2 FADH2, 2GTP (so each Acetyl CoA generates 5NADH, 1 FADH2, 1 GTP)

53
Q

How many ATPs do the 10 NADH and 2 FADH2 make respectively after reoxidation in the ETC?

A

30 ATP + 4 ATP

54
Q

So overall, including glycolysis, how many ATPs used and generated?

A

2 ATP used and (4 + 30 + 4) 38 ATP generated, and 2 GTP generated

55
Q

The 2 methods to transport electrons from NADH in the cytoplasm (glycolysis) into the mitochondrial matrix:

A
  1. Glycerol-phosphate Shuttle - skeletal muscle, brain

2. Malate-Aspartate Shuttle - heart, kidney, liver

56
Q

Glycerol Phosphate Shuttle:

A

Glycerol 3- phosphate dehydrogenase has 2 forms, one found in the cytosol, one found in the mitochondria.
The cytosolic glycerol 3-phosphate dehydrogenase transfers electrons from the NADH in the cytosol, to a molecule from stage 5 glycolysis, dihydroxyacetone phosphate (DHAP) to form glycerol 3-phosphate (G3P). The G3P then goes through the mitochondrial glycerol 3-phosphate dehydrogenase, which transfers electrons to FAD. They then get passed to co-enzyme Q, which is a part of the ETC.

57
Q

Transamination

A

An amine group is exchanged for a keto group

58
Q

Malate-Aspartate Shuttle:

A

The electrons from NADH are transferred to malate in the cytosol, which is able to travel into the mitochondria, and donate the electrons to NAD+ inside the mitochondria.
In the cytosol: Aspartate —-aspartate transaminase—-> oxaloacetate
Transamination
Oxaloacetate —-malate dehydrogenase—-> malate
Requires NADH which forms NAD+
Redox
The Malate is able to go into the mitochondria and the reverse reactions occur:
In the mitochondria: malate —-malate dehydrogenase—-> oxaloacetate
Requires NAD+ to form NADH
Redox
oxaloacetate —-aspartate trasminase—-> aspartate
The aspartate is able to the leave the mitochondria and enter the cytosol.

59
Q

Generic mechanism for amino acids to enter glycolysis / TCA:

A

Amino Acid Degradation
Deamination of the amino acid (removal of amine group) to leave behind the carbon skeleton. This is then funneled into the production of glucose or fed into the Krebs Cycle

60
Q

How many molecules does the degradation of all 20 amino acids result in?

A

7

Pyruvate, acetyl CoA, acetoacetyl CoA, a-ketoglutarate, succinyl CoA, fumarate and oxaloacetate

61
Q

Protein metabolism involves which main type of reaction?

A

Transamination - amine group from amino acid tranferred to keto acid, to form a new pair of amino and keto acids.
Group Transfer

62
Q

How is Alanine metabolised?

A

Alanine + a-ketoglutarate —-Alanine Aminotransferase(ALT)—-> pyruvate and glutamate
Pyruvate enters the TCA and the glutamate is converted to a-ketoglutarate by glutamate dehydrogenase, which removes the NH4+ group (that is eventually converted to urea).

63
Q

What does increased ALT levels in the blood indicate?

A

Problems with the liver

64
Q

Which 3 enzymes, if mutated, cause decreased TCA activity?

A

Isocitrate hydrogenase, succinate dehydrogenase, fumerase

65
Q

Why does decreased TCA activity increase chances of cancer?

A

Cancer cells respire anaerobically to get ATP

66
Q

What is the Warburg effect?

A

Mutations in those 3 enzymes can result in anaerobic respiration, despite high oxygen settings

67
Q

Using this knowledge (cancer cells respire anaerobically), what is a potential method to treat cancer cells?

A

Force them to undergo oxidative phosphorylation (aerobic respiration) for their supply of ATP, which may perhaps turn them non-malignant

Y1 - PoM - Week 1 (21 decks)

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