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Y1 Fundamentals of Life Science > L11: TCA cycle > Flashcards

L11: TCA cycle Flashcards

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1
Q

What is the energy cost of gluconeogenesis?

A
  • 4 ATP
  • 2 GTP
  • 2 NADH
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2
Q

Where is ATP used in gluconeogenesis?

A
  • Bypass 1 between pyruvate and oxaloacetate - uses 2 ATP as 2 molecules of pyruvate are used to produce 2 oxaloacetate
  • Uses 2 ATP between 3-phosphoglycerate and 1,3-bisphosphoglycerate - 2 molecules of each so 2 ATP
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3
Q

Where is GTP used in gluconeogenesis?

A
  • Bypass 1 between oxaloacetate and phosphoenolpyruvate
  • 2 molecules of phosphoenolpyruvate generated so 2 GTP used
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4
Q

Where is NADH used in gluconeogenesis?

A
  • Between 1,3-bisphosphoglycerate and glyceraldehyde-3-phosphate
  • Uses 2 NADH as 2 glyceraldehyde generated
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5
Q

Is glycolysis or gluconeogenesis more energy expensive?

A
  • Gluconeogenesis - uses 4 ATP, 2 GTP and 2 NADH
  • Glycolysis uses 2 ATP, but produces 2 ATP and 2 NADH
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6
Q

Where does the TCA cycle take place?

A

Mitochondrial matrix

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7
Q

What conditions are required for the TCA cycle?

A

Aerobic conditions

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8
Q

What is the importance of the TCA cycle?

A
  • Final common pathway for oxidation of fuel molecules: amino acids, fatty acids, carbohydrates
  • Important supply of intermediates for biosynthesis - e.g. to generate nucleotides, amino acids and metabolites
  • Important for production of energy
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9
Q

What molecule acts on pyruvate when it enters the mitochondria?

A

Pyruvate dehydrogenase (PDH)

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10
Q

What is pyruvate dehydrogenase?

A
  • Multienzyme complex in the mitochondrial matrix
  • Consists of 3 distinct enzyme - pyruvate decarboxylase (E1), dihydrolipoyl transacetylase (E2), dihydrolipoyl dehydrogenase (E3)
  • Uses vitamin B1 as a cofactor
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11
Q

What is the main function of pyruvate dehydrogenase?

A

Catalyses the irreversible oxidative decarboxylation of pyruvate to produce acetyl CoA, CO2 (and NADH)

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12
Q

Where is pyruvate dehydrogenase found in the pathway for aerobic metabolism?

A
  • Pre-Krebs
  • Intermediate step before the Krebs cycle
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13
Q

Draw the mechanism for pyruvate into acetyl CoA. Include locations and molecules used and produced in the process

A
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14
Q

What important molecule is generated from the mechanism involving pyruvate dehydrogenase?

A
  • 2 molecules of NADH
  • No ATP here
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15
Q

What is energy requirements matching?

A
  • When there is not enough glucose available to be metabolised, other sources of energy as used, including fatty acids and glycerols from fats, and amino acids from proteins in muscle cells
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16
Q

Draw the TCA cycle (to include the names of molecules, enzymes and what is generated)

A
  • Citrate is a 6 carbon molecule
  • a-ketoglutarate is a 5 carbon molecule
  • Succinyl-CoA is a 4 carbon molecule
  • Oxaloacetate is a 4 carbon molecule
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17
Q

What are the two parts to the TCA cycle?

A
  • Control half - release of NADH and CO2
  • Regeneration half - regenerate oxaloacetate to interact with another molecule of CoA to start the cycle again
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18
Q

What is the order in which you get production of NADH and energy equivalence in the TCA cycle?

A
  • 2 Acetyl-CoA are used, as 2 pyruvate molecules are generated per glucose molecule so NADH and energy are double
  • Means 2 ATP/GTP, 6 NADH, and 2 FADH2
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19
Q

How many ATPs are generated per NADH?

A

2-3 ATPs

20
Q

How many ATPs are generated per FADH2?

A

1-2 ATPs

21
Q

What is substrate level phosphorylation?

A
  • The generation of ATP from ADP by the direct transfer of a high energy phosphate group from a substrate
  • Glycolysis investment phase and TCA cycle
22
Q

What is oxidative phosphorylation?

A
  • The generation of NADH and FADH2 to produce a certain number of ATP molecules
  • Glycolysis payoff phase and TCA cycle
23
Q

What is the electron transport chain?

A

Using proton pumps and electron transfer to generate energy using NADH and FADH2

24
Q

What are electron acceptors?

A
  • Accept electrons from NADH and FADH2
  • Couple NADH and FADH2 to transfer protons across the membrane
  • These are Complex 1, 2, 3, 4 and cytochrome C
25
Q

Describe the process of the electron transport chain (ETC)

A
  • Electrons from NADH and FADH (generated in glycolysis and the TCA cycle) pass along the ETC to O2 (which is reduced to water)
  • The ETC consists of a series of electron donors and acceptors (complexes) - each donor passes an electron to a more electronegative acceptor, a process that continues until the electrons are passed to O2, (the terminal acceptor in the chain)
  • NADH donates to complex 1 and FADH2 donates to complex 2 to start the process
  • Passage of electrons from donors to acceptors releases energy which is used to pump protons across the inner mitochondrial membrane to the intermembrane space
  • This generates an electrochemical proton gradient which is used by ATP synthase. Protons pumped from intermembrane space back into the mitochondrial matrix via ATP synthase generates ATP from ADP and Pi
26
Q

Why is cyanide so good as a toxin?

A
  • Cyanide inhibits cytochrome C oxidase
  • Stops the progression of the electron transport chain
  • Stops aerobic respiration
27
Q

How is ATP formed by the action of ATP synthase in the ETC?

A
  • ATP synthase is a complex of proteins
  • These proteins rotate around each other
  • This rotational force provides the energy to allow for the generation of ATP
28
Q

What is uncoupling protein 1 (UPC1)?

A
  • Channel protein expressed in the mitochondria of adipocytes in brown adipose tissue
  • Present in the inner mitochondrial membrane
  • Allows protons to cross the inner mitochondrial membrane without generating ATP
  • The metabolic activity associated with the futile cycling of protons across the inner mitochondrial membrane generates heat
  • Tightly regulated to ensure ATP is still generated by ATP synthase and doesn’t allow all protons through for heat generation
29
Q

Where is brown adipose tissue found?

A

Babies have a lot to keep themselves warm

30
Q

What processes are controlled in the fed state?

A
  • Key intermediates such as ATP, NADH, acetyl-CoA and citrate accumulate
  • ATP and citrate inhibit phosphofructokinase (PFK) allosterically causing glucose-6-phosphate to accumulate in times of high ATP
  • When there is low ATP, PFK is activated to produce more ATP
31
Q

What storage can occur when glucose-6-phosphate acumulates?

A
  • Glucose-6-phosphate can be switched to production of glycogen and pentoses (Pentose Phosphate Pathway, PPP) which produces NADPH
32
Q

What is the Pentose Phosphate Pathway?

A
  • 5 carbon sugars
  • Make NADPH
  • NADPH can donate electrons and hydride molecules in catabolic processes
33
Q

Why are fatty acids synthesised in this pathway?

A
  • Acetyl units can be drawn from the central pathway to synthesis fatty acids
  • When there is plenty of ATP/energy available
34
Q

How are fatty acids synthesised?

A
  • Requires transport of acetyl units across the mitochondrial membrane (acetyl shuttle/citrate, a transport protein) since this occurs in the cytosol
  • Acetyl CoA carboxylase is activated by citrate and insulin which allows the acetyl-CoA to be transported from the mitochondrial membrane to the cytosol
  • Requires Biotin as a cofactor, NADPH (PPP)
  • Fatty acids keep extending
35
Q

What is an ACP?

A
  • Acetyl carrier protein- holds the emerging chain together
36
Q

Where are the fatty acids stored?

A

Liver or adipose tissue to be used later

37
Q

Describe the process of fat metabolism (input into the central pathway)

A
  • Occurs when energy needs to be released from adipose stores when ATP and NADH is low and ADP and NAD are high
  • Triglycerides are fed into the central pathway and catalysed by a hormone sensitive lipase, activated by a cAMP responsive kinase and then transported
  • Inhibited by insulin - trying to recover as much glucose as possible
38
Q

What is the name of the process which carries out fat metabolism?

A

Beta oxidation

39
Q

Describe beta oxidataion

A
  • Fatty acids viewed as acetyl unit that are 2 carbon polymers (usually even number of carbons 12, 16, 18)
  • Can transport fatty acids into the mitochondria via the carnitine shuttle
  • Able to generate FAD and NAD which can yield 8 acetyl-CoA units which gives rise to 131 ATP
40
Q

Where are most energy requirements met from during low-moderate intensity exercise?

A

Energy requirements for muscle come from fatty acid oxidation with a small contribution from glucose oxidation

41
Q

Where are most energy requirements met from during high intensity exercise?

A

Glucose is an energy substrate during short-term intense exercise - lots of glycolysis

42
Q

What is urea formed of?

A
  • Proteins are acetyl units with nitrogen attached
  • Nitrogen becomes ammonia, which becomes urea and is excreted
43
Q

Where do different amino acids input into the TCA cycle?

A
44
Q

What is the key issue for amino acid metabolism by the central pathway?

A
  • a-amino acid can undergo transamination to form an a-keto acid (part of TCA cycle)
  • This uses a-ketoglutarate to allow for transamination - this is converted into glutamate
  • The a-ketoglutarate is part of the TCA cycle - needs to be maintained
  • The a-ketoglutarate is regenerates by glutamate undergoing oxidative deamination
  • This oxidative deamination forms ammonia and reacts with carbon dioxide to form urea
45
Q

Where does deamination occur? How is it activated?

A
  • In the mitochondrial matrix
  • Activated by low energy (ADP and GDP) and inhibited by high energy (ATP, NADH, GTP)
  • Last resort metabolite
46
Q

How is urea excreted? Where does this happen?

A
  • Occurs exclusively in the liver
  • The fumarate can re-enter the TCA cycle

Y1 Fundamentals of Life Science (17 decks)

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