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MCD - Metabolism > Metabolic Pathways and ATP Production 1 > Flashcards

Metabolic Pathways and ATP Production 1 Flashcards

1
Q

Sketch a cartoon of the 3 stages of cellular metabolism including cellular location

A

Check metabolism notes for diagram, cover and draw from memory, repeat when this card comes up

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2
Q

What are the 3 stages of cellular metabolism in order?

A

1) Glycolysis
2) TCA cycle
3) Oxidative phosphorylation

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3
Q

What is the effect of eating on metabolism?

A

Speeds it up

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4
Q

What is the effect of fasting on metabolism?

A

Slows it down

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5
Q

What are the steps involved in the first half of glycolysis? Include any enzymes involved

A

1) Glucose -> Glucose-6-P (ATP used) (hexokinase)
2) G-6-P -> Fructose-6-P (phosphoglucoisomerase)
3) F-6-P -> Fructose-1,6-bisphosphate (ATP used) (phosphofructokinase)
4) F-1,6-Bp -> Dihydroxyacetone phosphate (DHAP) + glyceraldehyde 3-phosphate (G-3-P) (aldolase)
5) DHAP -> G-3-P (triose phosphate isomerase)
Ends first half with two molecules of G3P

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6
Q

What are the steps involved in the second half of glycolysis? Include any enzymes involved

A

1) G3P -> 1,3 bisphosphoglycerate (NADH produced) (G3P dehydrogenase)
2) 1,3 bisphosphoglycerate -> 3-phosphoglycerate (generates ATP) (phosphoglycerate kinase)
3) 3-phosphoglycerate -> 2-phosphoglycerate (phosphoglycerate mutase)
4) 2-phosphoglycerate -> phosphoenolpyruvate (enolase)
5) Phosphoenolpyruvate -> pyruvate (generates ATP) (pyruvate kinase)
All of these steps occur twice for each molecule of glucose.

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7
Q

What is the net produce of glycolysis?

A

2 pyruvate, 2 ATP, 2 NADH

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8
Q

What are the 3 fates of pyruvate?

A

Alcoholic fermentation
Lactic acid generation
The Link Reaction

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9
Q

What happens in alcoholic fermentation?

Include any enzymes involved

A

Occurs in anaerobic conditions
Pyruvate –> Acetaldehyde (pyruvate decarboxylase)
Acetaldehyde –> ethanol (alcohol dehydrogenase)
NADH->NAD+

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10
Q

What happens in lactic acid generation? Include any enzymes involved

A

Occurs in anaerobic conditions
Pyruvate –> Lactate (lactate dehydrogenase)
Reversible reaction
NADH->NAD+

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11
Q

What happens in the link reaction? Include any enzymes involved

A

Occurs in mitochondrion, under aerobic conditions
Pyruvate + HS-CoA –> Acetyl CoA + CO2 (pyruvate dehydrogenase complex)
NAD+->NADH

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12
Q

What is the name for the metabolism process of fatty acids?

A

Beta-oxidation

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13
Q

What is the name for fatty acid biosynthesis?

A

Lipogenesis

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14
Q

Summarise the process of beta-oxidation

A

1) Fatty acid + HS-CoA + ATP –> Acyl CoA + AMP + PPi (two high energy bonds used) (occurs on the outer mitochondrial membrane)
2) Acyl CoA moved into mitochondrial matrix via carnitine shuttle.
3) Acyl CoA undergoes oxidation, hydration, oxidation again, then thiolysis. 1st oxidation = NADH produced. 2nd oxidation = FADH2 produced.
4) Shortened fatty acyl CoA and acetyl CoA produced. Fatty acyl CoA shortened by 2C every cycle apart from final cycle, 4C product produced.
5) Fatty acyl CoA starts cycle again. Acetyl CoA continues to krebs cycle.

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15
Q

State the net products of one cycle of beta-oxidation

A

1x Shortened fatty acyl CoA
1x Acetyl CoA
1x NADH
1x FADH2

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16
Q

State the locations of the steps of beta-oxidation

A
  • Fatty acid to acyl CoA occurs on outer mitochondrial membrane
  • Carnitine shuttle transfers across OMM
  • All other steps occur in mitochondrial matrix
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17
Q

Summarise the process of lipogenesis

A

1) Acetyl CoA -> Malonyl CoA (acetyl CoA carboxylase)
2) Malonyl CoA -> Malonyl ACP (malonyl-CoA-ACP-transferase)
3) Acetyl CoA -> Acetyl ACP (acetyl-CoA-ACP-transferase)
4) Acetyl ACP + Malonyl ACP -> acetoacetyl-ACP (CO2 produced)(beta-ketoacyl ACP synthase)
5) Acetoacetyl-ACP -> D-3-hydroxyacyl-ACP (beta-ketoacyl ACP reductase)
6) D-3-hydroxyacyl-ACP -> Trans-2-enoyl ACP (3-hydroxyacyl ACP reductase)
7) Trans-2-enoyl ACP -> butryl ACP (enoyl ACP reductase).
Steps 4-7 cycle until desired elongation is complete or 16C chain is reached.

18
Q

Give two examples of fatty acid metabolism disorders

A
  • Medium-chain-acyl-coenzyme A dehydrogenase deficiency (MCADD)
  • Primary carnitine deficiency
19
Q

Summarise medium-chain-acyl-coenzyme A dehydrogenase deficiency

A
  • Autosomal recessive disorder
  • Fatal if undiagnosed
  • Thought to account for 1/100 cases of sudden infant death syndrome
20
Q

Summarise primary carnitine deficiency

A
  • Autosomal recessive disorder
  • Mutation in SLCC22A5 gene encoding carnitine transporter
  • Results in reduced ability to uptake carnitine and as a result reduced beta-oxidation.
  • Symptoms appear in infancy/early childhood as encephalopathies, cardiomyopathies, muscle weakness, hypoglycaemia.
21
Q

Summarise how glucose can be converted to products for TCA cycle

A

Glycolysis

22
Q

Summarise how amino acids can be converted into products for TCA cycle

A

Degradation of amino acids - Amino group removed from amino acid so carbon skeleton fed into glycolysis or TCA cycle.
Transamination - Amino group transferred from AA to a keto acid, new pair of amino and keto acids formed.

23
Q

Summarise the TCA cycle

A

1) Oxaloacetate (4C) -> Citrate (6C) (citrate synthase)
2) Citrate (6C) -> Isocitrate (6C) (aconitase)
3) Isocitrate (6C) -> Alpha-ketoglutarate (5C) (CO2, NADH produced) (isocitrate dehydrogenase)
4) Alpha-ketoglutarate (5C) -> Succinyl-CoA (4C) (CO2, NADH produced) (alpha-ketoglutarate dehydrogenase complex)
5) Succinyl-CoA (4C) -> Succinate (4C) (GTP produced) (succinylcholine CoA synthetase)
6) Succinate (4C) -> Fumarate (4C) (succinate dehydrogenase, FADH2 produced)
7) Fumarate (4C) -> Malate (4C) (fumerase)
8) Malate (4C) -> (Oxaloacetate regenerated, NADH produced) (malate dehydrogenase)

24
Q

Where does the TCA cycle take place?

A

Mitochondrial matrix

25
Q

What are the net products of the TCA cycle?

A

3x NADH
2x CO2
1x FADH2
1x GTP

26
Q

Why are the glycerol-phosphate and malate-aspartate shuttles required?

A

NAD+ regeneration

27
Q

Where do the glycerol-phosphate and malate-aspartate shuttles operate?

A

Glycerol-phosphate - Skeletal muscle, brain

Malate-aspartate - Liver, kidney, and heart

28
Q

Summarise the process of the glycerol-phosphate shuttle

A

1) Dihydroxyacetone (DHAP) -> Glycerol 3-phosphate (G3P), takes place in cytosol. Generates NAD+
2) G3P enters mitochondrial matrix
3) G3P -> DHAP (generates FADH2 which donates H2 to coenzyme Q as part of ox.phosphorylation)
4) DHAP passes back out into cytosol, cycle repeats.

29
Q

Summarise the process of the malate-aspartate shuttle

A
  • Uses two membrane transporters
  • alpha-ketoglutarate transporter - exchanges alpha-ketoglutarate for malate.
  • glutamate-aspartate transporter - exchanges glutamate for aspartate.
    1) Oxaloacetate -> Malate (cytosol, malate dehydrogenase, NAD+ generated in cytosol)
    2) Malate exchanged in alpha-ketoglutarate transporter into mitochondrial matrix
    3) Malate transformed back into oxaloacetate by mitochondrial malate dehydrogenase generating NADH.
    4) Transamination occurs, glutamate + oxaloacetate -> alpha-ketoglutarate + aspartate.
    5) a-KG into Malate/alpha-KG transporter, aspartate into Glutamate, aspartate transporter.
    Cycle continues
30
Q

What is the electron transport chain?

A

A chain of three protein complexes and two mobile carriers which act as electron carriers

31
Q

List the 3 protein complexes in the electron transport chain

A

1) NADH dehydrogenase complex
2) Cytochrome b-c1 complex
3) Cytochrome oxidase complex

32
Q

What are the two mobile carriers in the electron transport chain?

A

1) Ubiquinone (a.k.a. co-enzyme Q) - carries electrons between protein complexes 1 and 2.
2) Cytochrome C - carries electrons between protein complexes 2 and 3.

33
Q

What is the function of the electron transport chain and how does it accomplish this?

A

Pumping of protons into the inter membrane space. Each protein accepts electrons, as the electrons pass through the complexes, a proton is passed or “pumped” into the intermembrane space.

34
Q

Explain the chemiosmotic model

A

Protons are moved into intermembrane space by energy generated from electron transport chain. The pumped protons move back down their electrochemical gradient through a specific channel, coupled to an enzyme called ATP synthase. The movement of the protons through the channel generates the energy to synthesise ATP.

35
Q

Summarise the structure of ATP and it uses and synthesise ATP

A
  • Multimeric enzyme
  • Has a membrane-bound part and F1 part projecting into matrix.
  • When protons are flowing into the mitochondrial matrix - ATP synthesis takes place.
  • When protons are flowing into intermembrane space - ATP is being used.
36
Q

List metabolic poisons

A 
Cyanide (CN-)
Azide (N3-)
Carbon Monoxide (CO)
Malonate
Oligomycin
Dinitrophenol
37
Q

Explain cyanide’s toxicity

A

Binds with high affinity to ferric (fe3+) form of haem group in cytochrome oxidase complex and blocks flow of electrons through transport chain.

38
Q

Explain azide’s toxicity

A

Bind with high affinity to ferric (fe3+) form of haem group in cytochrome oxidase complex and blocks flow of electrons through electron transport chain.

39
Q

Explain carbon monoxide’s toxicity

A

Binds to ferrous (fe2+) form of haem group in cytochrome oxidase complex, blocks flow of electrons through transport chain.

40
Q

Explain malonate’s toxicity

A

Closely resembles succinate
Competitive inhibitor of succinate dehydrogenase
Slows flow of electrons from succinate to ubiquinone so fewer electrons being passed into electron transport chain.

41
Q

Explain oligomycin’s toxicity

A

Inhibits oxidative phosphorylation

Binds to stalk of ATP synthase, blocking flow of electrons through the enzyme - ATP synthesis inhibited.

42
Q

Explain Dinitrophenol’s toxicity

A

Transports H+ across mitochondrial membrane before they reach ATP synthase channel - therefore uncouples ox. phosphorylation from ATP production.

MCD - Metabolism (5 decks)

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