7 Metabolism Flashcards

1
Q

What is a metabolic pathway?

A

Series of enzyme-catalyzed reactions

  • metabolites or metabolic intermediates are the chemical intermediates
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2
Q

The chemical intermediates of metabolic pathways are called:

A

Metabolites or Metabolic intermediates

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3
Q

All metabolic pathways share the same ________ and _________ principles

A

All metabolic pathways share the same fundamental chemical and thermodynamic principles

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4
Q

What are the two major purposes of Metabolism?

A
  1. To obtain usable chemical energy from the environment
    • capturing solar energy (photosynthesis)
    • Consuming and breaking down nutrient molecules
  2. To make the specific molecules that cells need to live and grow
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5
Q

Differences between cells in different organisms and different tissues come down to differences in their ________

A

Differences between cells in different organisms and different tissues come down to differences in their metabolic pathways

  • active sets of pathways determine function
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6
Q

What are anabolic pathways?

A

Pathways that use energy (require energy) to build larger molecules and are generally reductive (electrons are used to make new bonds)

  • Biosynthesis
  • Require precursors
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7
Q

What are catabolic pathways?

A

Release energy (some of which is stored) and are generally oxidative (electrons are removed as bonds are broken)

  • generates precursors (building blocks)
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8
Q

What are amphibolic pathways?

A

Operate in both catabolic and anabolic processes (depending on conditions)

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9
Q

Three ways food can be used in metabolism?

A
  1. Generate oxidized carbon atoms (CO2) and water = catabolism
  2. Generate metabolic intermediates for formation of cellular constituents (Anabolism)
  3. Storage of energy as ATP (electrons as reduced cofactors for anabolism)
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10
Q

What are the four dietary macromolecules?

What do they break down into?

A
  • Nucleic acids
    • nucleotides
    • not a significant fuel source
  • Proteins
    • amino acids
  • Polysaccharides (complex carbs)
    • monosaccharides (simple sugars)
  • Triacylglycerol (Fat)
    • fatty acids
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11
Q

Which two dietary macromolecules are the most significant fuel sources (ie greatest energy)?

A

Polysaccharides and Triacylglycerol

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12
Q

Are proteins used as an energy source?

A

Not typically. We can, but the amino acids are better used elsewhere

  • We use the amino acids from protein breakdown for the synthesis of our own proteins
  • Some amino acids we can only get from outside sources
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13
Q

Between polysaccharides and triacylglycerol, which provides more energy?

A

Triacylglycerol (fat) provides more energy than polysaccharides (carbohydrates) but both represent significant fuel sources.

Both are less useful as precursors than they are as energy sources

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14
Q

What is something that we ALWAYS need?

A

ATP/energy

Food is catabolyzed into ATP

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15
Q

What happens in the absence of food?

A

Fuel stores are mobilized to generate fuel molecules which can be catabolized to form ATP

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16
Q

The way we store fuel molecules depends on ________

A

The way we store fuel molecules depends on the type of molecules in question

  • Major ways:
    • As carbohydrates
    • As fats
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17
Q

Carbohydrates are generally stored as _________ in the _________ and ________

A

Carbohydrates are generally stored as glycogen (polymer of glucose molecules) in the liver (hepatocytes) and skeletal muscle (myocytes)

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18
Q

Fatty acids are stored as ______ in _________

A

Fatty acids are stored as fat (triacylglycerols) in adipocytes

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19
Q

Liver glycogen is used to maintain:

Skeletal muscle glycogen is used for:

A

Liver glycogen is used to maintain a Continuous glucose supply in the bloodstream.

Skeletal muscle glycogen is used for those myocytes = not available for the rest of the body

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20
Q

Which stores more energy, fat or carbohydrates?

A

Fat (1g:7g ratio)

Fat can store the same amount of energy in one gram as carbohydrates can in 7g

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21
Q

What is the biochemical standard state?

(what the prime ‘ refers to in deltaG)

A
  • pH 7 ([H+] = 10^-7 M)
    • (for chemical standard state, [H+] = 1 M)
  • [Substrates] & [Products] = 1M
    • consistent with chemical standard state
  • Temperature = 25°C/298K
  • Pressure = 1atm
  • [H2O] = 55M
    • (large amount of water)

IGNORE [H+] and [H2O] in calculations

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22
Q

A reaction will only proceed in the forward direction when the associated value of deltaGreaction is _______

A

A reaction will only proceed in the forward direction when the associated value of deltaGreaction is negative (<0)

  • ACTUAL delta G (not the standard delta G)
  • ΔG’reaction = biochemical actual
  • ΔG’°reaction = biochemical standard
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23
Q

What is the difference between:

ΔG’reaction

ΔG’°reaction

A

ΔG’reaction = biochemical actual free energy change

ΔG’°reaction = biochemical standard free energy change

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24
Q

How would you describe a reaction with

ΔG’reaction < 0

A

ΔG’reaction < 0

Reaction is:

  • exergonic
  • spontaneous
  • “down-hill”
  • Favourable
  • Reaction proceeds forward
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25
Q

What will the reaction look like for each of the following free energies?

  • ΔG’reaction > 0
  • ΔG’reaction < 0
  • ΔG’reaction << 0
  • ΔG’reaction ~ 0
A
  • ΔG’reaction > 0
    • Reaction will not occur in the forward direction
  • ΔG’reaction < 0
    • Reaction will occur (spontaneous)
  • ΔG’reaction << 0
    • Reaction may be considered irreversible (A → B)
    • if reaction is always negative under physiological conditions
  • ΔG’reaction ~ 0
    • Reaction is considered reversible
    • Close to Equilibrium (B←→C)
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26
Q

A metabolic pathway is a series of __________ and each individual rxn must obey __________

A

A metabolic pathway is a series of enzyme-catalyzed chemical reactions and each individual rxn must obey thermodynamic laws

  • Free energy change must be negative (ΔG <0)
  • ΔG = ΔH -TΔS
  • ΔG = ΔG°’ + RTln( [products] / [reactants] )
  • the net free energy change for the pathway must be negative for a pathway to proceed
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27
Q

True or false:

Both catabolic and anabolic pathways require a Net ΔG<0 for a pathway to proceed

A

True

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28
Q

Metabolic pathways exist in a ________ (concentrations of metabolic intermediates often don’t change significantly)

A

Metabolic pathways exist in a steady-state

  • Water example: as long as water coming in is equal to water out, the pool stays at constant level (steady state)
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29
Q

Which steps of a metabolic pathway are typically regulated?

A
  • Irreversible steps are usually regulated
  • Reversible steps are not usually regulated
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30
Q

What is the “rate-limiting step”?

A

The rate-limiting step in a pathway is the irreversible, regulated reaction that determines the overall rate of the pathway

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31
Q

Which enzymes in the image would you expect to be regulated?

A

Enzymes E1 and E4 are likely to be regulated

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32
Q

What is product inhibition?

A

When our enzyme is inhibited by the immediate product of its reaction

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33
Q

What is feedback inhibition?

A

An enzyme is inhibited by a metabolite further down the pathway

34
Q

What is the image depicting?

A

Activation of an enzyme by a metabolite “upstream”

35
Q

What does feed-forward activation ensure?

A

Activation ensures that the pathway is functioning in concert (otherwise intermediates may accumulate)

“feed-forward activation”

(Allosteric patterns of activation)

36
Q

Feed-forward activation and Feed-back inhibition are examples of ________ regulation.

A

Feed-forward activation and Feed-back inhibition are examples of allosteric regulation

  • Feed-forward activation = positive heteroallostery
  • Feedback inhibition = negative heteroallostery
37
Q

Opposing pathways catalyze the “reverse” of another pathway, but what has to happen if there are any irreversible steps?

A
  • the irreversible reactions must be replaced or bypassed
    • eg Using ATP to reverse the reaction
38
Q

What is reciprocal regulation?

A

Pathways are regulated to ensure that both do not operate simultaneously.

Ie allows us to have simultaneous control over both pathways (something that might activate E1 and inactive E6)

  • eg liver can reversibly convert glucose to pyruvate but if both pathways are operating simultaneously, we would be wasting energy
  • ATP hydrolysis would occur but nothing would be achieved
39
Q

How might reciprocal regulation be achieved?

A
  • Enzyme regulators
  • Phosphorylation

There are different patterns of regulation

40
Q

What is a high-energy intermediate?

A

A molecule that contains usable energy of some kind

Ie Compounds which contain “usable” chemical energy

  • Energy can be recovered or used
  • Simple reaction associated with large delta G (>20kJ/mol released)
41
Q

What are the three major types of high-energy intermediates?

A
  1. Electron carriers (NADH, NADPH, FADH2, FMNH2) (reduced cofactors)
    • NAD+, NADP+, FAD, FMN are electron acceptors (oxidized forms)
  2. Nucleotide triphosphates (NTPs: ATP, UTP, GTP)
  3. Thioesters
42
Q

Nucleotide triphosphates have a large free energy change associated with _______ of the ________ bond

A

Nucleotide triphosphates (ATP, GTP) have a large free energy change associated with hydrolysis of the phosphoanhydride bond

43
Q

How is a thioester formed?

A

Thioester = looks like an ester but has a Sulfur as part of the ether linkage

Formed from condensation of carboxylic acid and Thiol

44
Q

Hydrolysis of a thioester would yield:

(Energy change?)

A

A carboxylate and a thiol (HS-R’’)

  • delta G°’ ~ 30kJ/mol (comparable to ATP hydrolysis)
45
Q

Catabolic processes are _________ (oxidative or reductive)

A

Catabolic processes are Oxidative (oxidative or reductive)

  • Metabolites are oxidized (lose electrons)
  • Cofactors are reduced
  • Typically NAD+ (oxidation of C-O bonds), FAD (C-C bonds)
    • become reduced
    • Accept electrons
46
Q

Anabolic process are _________ (reductive or oxidative?)

A

Anabolic processes are reductive

  • Metabolites are reduced (gain electrons)
  • Cofactors are oxidized (reducing agents - becoming oxidized)
  • Typically NADPH (electron carrier)
    • NADH/FADH2 also involved in reduction reactions
    • Reduced cofactors become oxidized during reaction
47
Q

Nucleotides play a central role in metabolism as electron _______

A

Nucleotides play a central role in metabolism as electron carriers

  • NAD+
    • Nicotinamide adenine dinucleotide
  • FAD
    • Flavin adenine dinucleotide
  • The nitrogen base portion of these dinucleotides enables them to undergo a reversible reduction reaction
48
Q

What characteristic of NAD+ and FAD allows them to undergo a reversible reduction reaction?

A

The nitrogen base portion (Non-adenine) (nicotinamide or flavin rings)

49
Q

What can we determine about NAD+ based on the image?

A

NAD+ is a dinucleotide

  • base, sugar, phosphate joined together by a phosphoanhydride bond
  • No directionality because it’s a 5’ to 5’ linkage (unlike 5’ -> 3’ in nucleic acids)
50
Q

What is the difference between NAD+/NADH and NADP+/NADPH

A

Whether or not there is a phosphate attached to the 2’ position on the adenosine nucleotide portion of the molecule

51
Q

What is the Net charge of NAD+ (NADP+)

A
  • Nicotinamide base carries a positive charge
  • both phosphate groups carry negative charge
  • Net Negative charge
    • NAD+ (+ = oxidized)
52
Q

What is a difference between the reduction of FAD and the reduction of NAD+

A

FAD takes up 2H+ and 2e- to become reduced

NAD+ takes up 1H+ and 2e- to become reduced

53
Q

What is the molecule in the image?

A

FAD

54
Q

NAD+ and NADP+ are typically _______ while FAD is a _______ group

A

NAD+ and NADP+ are typically cosubstrates while FAD is a prosthetic group

55
Q

Implications of the statement: NAD+ and NADP+ are typically cosubstrates while FAD is a prosthetic group

A
  • NAD+ being a cosubstrate means it can be reduced NADH and then dissociate from enzyme active site and if a reaction is to proceed in oxidative direction (catabolic pathway) then we can’t just let the [NADH] accumulate there has to be another process to oxidize that cofactor back to NAD+
    • For a cosubstrate that means it dissociates and then oxidation happens
    • On the other hand, FAD being a Prosthetic group has to be oxidized back to original state in order for enzyme to continue normal functioning
56
Q

What is implied about the function of FAD/FADH2 as a prosthetic group?

A

As a prosthetic group, FADH2 must be reoxidized back to FAD for the next enzyme cycle to occur.

  • eg in the citric acid cycle, coenzyme Q is used to carry out this reoxidation
57
Q

FAD is often involved in ______ bond oxidation

A

C-C

(single to double)

58
Q

ATP is a high energy compound because of _____________ bonds

A

ATP is a high energy compound because of phosphoanhydride bonds (2)

59
Q

What results if you hydrolyze one of the phosphoanhydride bonds in ATP?

A

There is a large negative free energy change associated with the hydrolyses process

  • delta G (ΔG’°) ~-32 kJ/mol for the hydrolysis of a phosphoanydride bond
  • ΔG’° ~ +32 kJ/mol for the formation of a phosphoanydride bond
60
Q

What is the free energy change for the formation and hydrolysis of a phosphoanhydride bond?

A
  • delta G (ΔG’°) ~-32 kJ/mol for the hydrolysis of a phosphoanydride bond
  • ΔG’° ~ +32 kJ/mol for the formation of a phosphoanydride bond (requires energy)
61
Q

What is it about ATP (phosphoanydride bonds) that make it high energy?

A
  1. Decreased electrostatic repulsion
    • ATP has a high number of negative charges focussed near each other
    • Hydrolysis reduces the number of negative charges
  2. Resonance stabilization
    • lowers free energy associated with formation of that particular molecule
  3. Solvation effects
    • one big molecule -> two smaller molecules = entropically more favourable (can better associate with water)
62
Q

Compare resonance stabilization of Terminal phosphoryl group of ATP and Inorganic Phosphate (Pi)

A
  • Terminal phosphoryl group of ATP
    • 3 resonance structures
  • Inorganic Phosphate
    • 4 resonance structures
      • 4Oxygens, all of which are roughly equivalent to eachother
        • proton (H+) weakly associated with phosphate group = not formally attached to any Oxygen
63
Q

What is a Thioester?

A
  • High energy compound
  • Similar to esters but with no e- delocalization
    • increased energy of substrates
  • hydrolysis of thioester is associated with Same kind of energy change as hydrolysis of phosphoanhydride bond (ATP) (delta G’°~30 kj/mol)
64
Q

Why are thioesters high-energy compounds while esters are not?

A
  • No delocalization of electrons in thioesters
    • substrates in thioester have a higher energy than the substrates in esters
    • Because energy starts higher, the free energy change (delta G) is MORE NEGATIVE for thioesters (see graph in image)
65
Q

ATP is generated by __________ (catabolism or anabolism)

A

ATP is generated by catabolism

66
Q

ATP is generated by catabolism:

May be generated by which two means?

A

ATP is generated by catabolism:

May be generated

  • directly: “substrate-level phosphorylation”
    • Direct product of a chemical reaction
  • Oxidative Phosphorylation
    • Via reoxidation of NADH/FADH2
67
Q

What are three ways ATP might be used?

A
  • Driving unfavourable reactions (coupling)
    • coupling = reactions that require input if energy
  • Movement (muscle, flagella)
    • hydrolysis of ATP
    • chemical energy into kinetic energy
  • Primary Active Transport
    • Variation of coupling
      • Taking an unfavourable process and using energy to drive it
68
Q

Analyze the graph

A
  • Graph illustrates the negative free energy change associated with the hydrolysis of ATP (delta G’° = -32kJ/mol
69
Q

What is the first reaction in glycolysis?

What is the free energy associated with that reaction?

How do we make it proceed in the forward direction under standard conditions?

A

The phosphorylation of glucose to form glucose-6-Phosphate

  • Free energy:
    • If we just add a Pi to glucose, the free energy associated with the reaction is positive 14kJ/mol (delta G > 0 = unfavourable)
      • won’t proceed in forward direction under standard conditions
    • If we add ATP to glucose the associated free energy change is the sum of the two reactions (-32 + 14 = -18kj/mol)
      • delta G < 0 is favourable = will proceed in forward direction
  • Coupling synthesis of glucose-6-phosphate to the hydrolysis of ATP
    • no actual hydrolysis as the Pi from ATP is being directly transferred to glucose
70
Q

What is the free energy associated with the phosphorylation of glucose to form glucose-6-phosphate in glycolysis? Will this reaction proceed in the forward direction under standard conditions?

A
  • Free energy:
    • If we simply add a Pi to glucose, the free energy associated with that reaction is positive 14kJ/mol (delta G > 0 = unfavourable)
      • won’t proceed in the forward direction under standard conditions
    • If we add ATP to glucose the associated free energy change is the sum of the two reactions (-32 + 14 = -18kj/mol)
      • delta G < 0 is favourable = will proceed in forward direction
  • Coupling synthesis of glucose-6-phosphate to the hydrolysis of ATP
    • no actual hydrolysis as the Pi from ATP is being directly transferred to glucose
71
Q

How is ATP used in the synthesis of glucose-6-phosphate during glycolysis?

A

Coupling synthesis of glucose-6-phosphate to the hydrolysis of ATP

  • no actual hydrolysis as the Pi from ATP is being directly transferred to glucose
72
Q

Free energy changes for reactions are _______. Combined reactions must have a NET free energy change _____ than 0 to be spontaneous.

A

Free energy changes for reactions are additive. Combined reactions must have a NET free energy change less than 0 (ΔG’°

73
Q

What is “Phosphate transfer potential”?

A

Phosphate-transfer potential refers to free energies of hydrolysis for phosphate-containing compounds

74
Q

Name the two glycolysis intermediates given in lecture that have phosphate transfer potential. What are their free energies of hydrolysis?

A
  1. Phosphoenolpyruvate ΔG’° = -62 kj/mol
  2. 1,3-Bisphosphoglycerate ΔG’° = -49 kj/mol
75
Q

What compound with phosphate transfer potential is a short term supply of ATP in muscle?

A

Phosphocreatine ΔG’° = -43 kj/mol

76
Q

Acetyl CoA is a ________ with phosphate transfer potential of _______

A

Acetyl CoA is a thioester with phosphate transfer potential of Δ​G’° = -32 kj/mol

77
Q

The hydrolysis of phosphocreatine produces:

A

creatine and Pi

78
Q

The polar head group (functional group) of creatine is derived from __________ and has a partial ______ charge distribution associated with all the Nitrogens because of _________\_

A

The polar head group (functional group) of creatine is derived from a guanido group (The basic-group configuration C = (NH2)2 found in arginine​) and has a partial positive charge distribution around all the Nitrogens because of ​resonance stabilization associated with that functional group

79
Q

What is the overall free energy change (ΔG’°) associated with the coupled reaction of phosphocreatine and ADP

Phosphocreatine + ADP ←→ creatine + ATP

A

Reaction 1: ADP + Pi + H+ -> ATP + H20 = phosphorylation of ATP: ΔG’°= +32

Reaction 2: Phosphocreatine + H2O → creatine + Pi : ΔG’°= -43

Therefore, the NET free energy change = -43 + 32 = -11kj/mol

80
Q

Why is the coupled reaction of phosphocreatine to creatine and ADP to ATP reversible under actual conditions?

A
  • [ATP] and [Phosphocreatine] and [creatine] are not going to at 1.0M
  • Phosphocreatine acts as a temporary store of chemical energy
    • when ↑[ATP] the reaction favours the formation of phosphocreatine
81
Q

What are four sources of ATP based on time and accessibility?

A
  • ATP on hand:
    • Immediately available
    • Lasts a couple seconds
    • “throw something”
  • ATP from Phosphocreatine
    • Provides ATP after the on-hand ATP has been used up
    • lasts a few seconds
  • ATP from Anaerobic processes
    • Substrate level phosphorylation processes
  • ATP from Aerobic processes
    • Generates significant amounts of sustainable ATP over extended period of time