Metabolism Flashcards

1
Q

Metabolism

A
  • the total of ALL chemical reaction in a cell

- 2000 reactions in a cell at any point

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2
Q

Metabolic pathway

A
  • a sequence of chemical reactions
  • enzymes in the same metabolic pathway are physically linked
    • together or part of cytoskeleton

-cell will couple exergonic and endergonic reactions

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3
Q

Anabolic pathways

A
  • synthesis of more complex compounds
  • endergonic (requires energy: +G)
  • e.g. amino acids joining via peptide bonds to make a protein
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4
Q

Catabolic

A
  • breaking down of complex molecules
  • exergonic (release energy: -G)
  • e.g. breakdown of glucose to pyruvate via glycolysis
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5
Q

ATP

A
  • adenosine triphosphate
  • energy currency of the cell
  • contains:
    • an adenine nitrogenous base
    • a ribose (5C sugar)
    • a triphosphate molecule
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6
Q

Hydrolysis of ATP

A

ATP + H2O —> ADP + Pi

Delta G = -7.3 kcal/mol

  • this energy available for the cell to do work
  • each cell uses 1-2billion ATP per day
  • why is this exergonic?
    1. Charge repulsion (close proximity of neg. charge on PO4-)
    2. Resonance stabilization
    3. Increased entropy
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7
Q

To make ATP

A
  • to make ATP the cell uses Redox reactions
    • transfer of electrons and hydrogen atoms from one compound to another
  • OXIDATION is LOSS of elections (and usually H)
  • REDUCTION is GAIN of electrons (and usually H)
  • ALWAYS COUPLED
  • glucose can be oxidized in a highly exergonic reaction which is used to make ATP
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8
Q

Complete oxidation of glucose

A

C6H12O6 + 6O2 —> 6CO2 + 6H2O + Energy

Delta G = -686 kcal/mol

  • cells only 40% efficient at producing ATP
  • energy = ATP + heat
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9
Q

Glycolysis

A

-occurs in the cytoplasm

  • starts with 6C: Glucose
  • finishes with 2x 3C: 2 pyruvates
  • investment of 2ATP at the beginning of glycolysis
  • a total of 4 ATP produced (via SUBSTRATE LEVEL PHOSPH.)
    • NET GAIN = 2 ATP

-2 NADH are made

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10
Q

NAD+

A
  • nicotinamide adenine dinucleotide
  • a non-protein coenzyme
  • an electron carrier
  • carries 2 ELECTRONS and 1 HYDROGEN
  • NAD+ = OXIDIZED form (no e- attached)
  • NADH = REDUCED form (e- attached)
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11
Q

Glycolysis products

A

1 Glucose =

2 Pyruvate
2 ATP (net gain)
2 NADH

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12
Q

Is there oxygen available after glycolysis?

A

YES —> aerobic respiration (pyruvate go to mitochondria, TCA etc.)

NO —> fermentation/anaerobic (allows for sustained generation of little ATP via glycolysis) Pyruvate is reduced
-we get some ATP from glycolysis but ONLY if NAD+ available

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13
Q

Fermentation

A
  • Regenerates NAD+
  • lactic fermentation
  • alcoholic fermentation
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14
Q

Lactic fermentation

A
  • after glycolysis, 2 pyruvate molecules REDUCED to 2 lactate molecules
  • produces 2 NAD+ (for glycolysis to continue)
  • occurs in muscle cells during intense activity
  • used to make dairy products
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15
Q

Alcoholic fermentation

A
  • 2 step process
  • 2 pyruvate —> 2 acetaldehyde
    • 2CO2 as byproduct
  • 2 acetaldehyde reduced to 2 ethanol
    • 2NAD+ generated
  • kombucha = alcoholic fermented tea
    • CO2 byproduct makes it fizzy
    • acetic acid
  • yeast
  • all alcohol
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16
Q

Cancer cells

A
  • cancer cells ferment glucose to lactate even in the presence of oxygen
  • possibly to make it into a product that still has a carbon skeleton to that it can be used as a precursor for essential molecules for growth
  • PET scans use a radioactive glucose analog to find cancer cells
17
Q

Mitochondria

A
  • where ATP synthesis occurs
  • mitochondria are dynamic
    • often exist as interconnected structures
  • mitochondria fuse and divide
    • ER plays important role in fission
18
Q

Mitochondrial fission

A
  1. ER interacts and recruits Drp1
  2. Drp1 forms helix around mitochondrion
  3. Mitochondrion splits
19
Q

Porins

A
  • channels that permit moderately sized molecules to move from the CYSTOL to INTERMEMBRANE SPACE
  • in outer mitochondrial membrane
  • ATP, pyruvate, NADH can travel through porin

-made of BETA PLEATED SHEETS

20
Q

Inner mitochondrial membrane

A
  • 3:1 protein:lipid ration (by weight)
  • well insulated
  • F1 particles (8.5nm)

-cardiolipin

21
Q

Cardiolipin

A
  • unusual lipid in the inner membrane
  • “double” phospholipid
  • has 4 fatty acid chains
  • called diphosphatidylglycerol

-INSULATES the membrane and makes it IMPERMEABLE

22
Q

The matrix

A
  • central compartment
  • high concentrations of proteins
  • site of TCA cycle
  • contains ribosomes and circular DNA
  • have all the machinery needed to transcribe/translate own proteins but only make about 5% of what they need
    • everything else is imported
    • endosymbiont theory
23
Q

Endosymbiont theory

A
  • Lynn Margulis (1960s)
  • theory of how mitochondrial double membranes were formed
  • small, aerobic prokaryote engulfed by large, anaerobic eukaryote to create double membrane
  • explains:
    1. Why it might have circular DNA
    2. Presence of ribosomes
    3. Presence of 2 membrane
24
Q

Oxidation of pyruvate

A
  • pyruvate moves into the mitochondrion through porins (actively transported into the matrix)
  • reaction is catalyzed by pyruvate dehydrogenase
25
Q

Products of oxidation of pyruvate

A

-per 1 pyruvate:

  • 1 CO2
  • 1 acetyl CoA
  • 1 NADH

-but there are 2 pyruvate made from glycolysis of one glucose

26
Q

TCA cycle

A

-occurs in the matrix of mitochondria

  1. CoA group leaves Acetyl
  2. Acetyl attaches to oxaloacetate —> citrate
  3. 2 CO2 molecules removed
  4. 3 NADH produced
  5. 1 FADH2 produced
  6. 1 GTP/ATP made
  7. Oxaloacetate regenerated
27
Q

FADH2

A

-flavin adenine dinucleotide

  • FAD+ = OXIDIZED form
  • FADH2 = REDUCED form
  • carries 2 electrons and 2 Hydrogens
  • electrons have slightly less energy than ones carries by NADH
28
Q

SO FAR after glycolysis, oxidation of pyruvate, and TCA

A

-NADH = 10
2 from glycolysis
2 from pyruvate oxidation
6 from TCA

-FASH2 = 2
2 from TCA cycle

-CO2 = 6
2 from pyruvate oxidation
4 from TCA cycle

-ATP = 4
2 from glycolysis
2 from TCA cycle

29
Q

Oxidative phosphorylation

A

-production of ATP using energy derived from redox reaction in the ETC

30
Q

ETC

A
  • electron transport chain
  • 4 complexes + ubiquinone + cytochrome C
  • occurs in the INNER MEMBRANE of mitochondria
  • series of redox reactions
  • uses electrons from NADH and FADH2
  • each complex has increasing redox potential (ability to acquire electrons
  • energy is released every time an electron is passed to the next complex
  • ETC is a target for many POISONS
31
Q

ETC process

A
  1. Complex 1: NADH dehydrogenase
    • oxidizes NADH —> NAD+ (2e-)
    • 4H+ pumped to IMS
  2. Ubiquinone (CoQ) transports those 2e- to Complex III
    • 4H+ pumped to IMS
    • hydrophobic: floats inside membrane
  3. Ctyochrome C transports the 2e- from complex III to Complex IV
  4. Complex IV: cytochrome C: proton pump, oxidized
    • receives e- and they leave to enable formation of water
    • Oxygen acts as final e- acceptor (reduced to H2O)
  5. Complex II: succinate dehydrogenase
    • makes FADH2
    • feeds e- to Complex III
    • succinate —> fumarate
32
Q

Chemiosmotic Theory

A
  • Peter Mitchel
  • Nobel prize 1978

-H+ gradient provides the energy to phosphorylate ADP to synthesize ATP

  • proton gradient made up by:
    1. Concentration difference (pH)
    2. Charge difference (voltage)
  • membrane is IMPERMEABLE to H+ ions
  • electrochemical gradient results in PROTON MOTIVE FORCE
33
Q

ATP Synthase

A
  • contains F1 particles (8.5nm) and F0
  • F0 composed of
    • 10 c units (which rotate)
    • 2 B units (arms for structure)
    • 1 a unit (for structure)
  • F1 composed of
    • 3 alpha units alternating with 3 beta units
    • gamma unit (long banana shape that turns… stalk like
34
Q

Binding change mechanism

A
  • Paul Boyer
  • Nobel prize 1997

-H+ enter in one channel, bind to C units, complete one full turn, and exit through a separate channel into the matrix

  • in F1 unit, Beta units have important function
    • as gamma subunit turns it causes conformational changes in Beta subunits
      1. O = Open… ADP + Pi enter
      2. L = Loose… ADP and Pi loosely attached
      3. T = Tight… ADP + Pi —> ATP spontaneously due to close interaction
35
Q

Ionophores

A
  • allow protons to leak across the membrane and bypass ATP synthase
  • hydrophobic weak acids
    • move though inner membrane and take H+ to matrix
  • uncouplers: uncoupling oxidation of glucose from formation of ATP
  • e.g. 2,4-dintrophenol (DNP)