Fuel Oxidation and ATP generation Flashcards

1
Q

What’s the point of ATP

A

ATP contains “high energy” phosphate bonds we use that energy to: -muscle contraction -active ion transport -biosynthesis -detoxificaion -thermogenesis

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2
Q

(ΔG) for a reaction

A

free energy change depends on temperature and on the concentration of the products and the substrates when the rxn is at equilibrium

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3
Q

What does ΔG>0 mean?

A

at equilibrium the reactants are favored, so it needs external help to proceed

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4
Q

ATP hydrolysis coupled to change in transporter conformation. Costs energy to move ions against electrochemical gradient.

A

Transport work: Na+/K+ -ATPase

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5
Q

*ATP hydrolysis coupled to change in protein conformation.

A

Mechanical work: muscle contraction

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6
Q

ATP hydrolysis coupled to change in enzyme conformation.

A

Synthesis (work): asparagine synthetase -ATP activating the enzyme

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7
Q

only type that ATP physically participates in the reaction itself (adds a phosphate to the reactant.

A

Biochemical work: glucose to G6P (its phosphorylation, so the enzymes will be kinases)

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8
Q

Molecules with phosphate or thioester linkage have high energy bonds, so?

A

We can cleave these to release a lot of energy (couple it to rxn we want to drive forward!)

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9
Q

What fuels can we get the most energy from?

A

**FA least oxidizes relative to number of carbons. glucose is the worst- most oxidized

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10
Q

Name 2 electron carriers that capture energy from oxidized fuels, and what is used to synthesize each?

A

NAD+ - made via niacin FAD+ - made via riboflavin *buzz word: dehydrogenase reactions

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11
Q

name 2 metabolic byproducts of fuel oxidation and ATP generation

A

-H20 (formed when oxygen molecules - the final electron acceptors of cellular resp. - take up protons) -CO2 (TCA cycle)

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12
Q

What is another term for glycolysis?

A

anaerobic metabolism -doesnt require oxygen or mitochondria -reducing pyruvate to lactic acid regenerates the electron carriers -takes place in cytosol -RBCs, WBCs, Kidney medulla, eye tissue -skeletal muscle (white fibers!)

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13
Q

What is another term for oxidative phosphorylation?

A

aerobic metabolism -takes place in mitochondria -requires mitochondria and oxygen -skeletal muscle (red fibers), most tissues of the body

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14
Q

Products of glycolysis

A

-2ATP -Lactic ACID -NAD+ -FAD+

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15
Q

Products of oxidative phosphorylation

A

-28 ATP -o2 (final electron acceptor)

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16
Q

Glycolysis investment phase

A

a

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17
Q

What are the 2 regulated steps in the investment phase of glycolysis, and why are they regulated?

A

conversion of glucose to G6P (currency of cell!) -*hexokinase is the enzyme that accomplishes phosphorylation conversion of fructose 6 phosphate to fructose 1,6 bisphosphate -*phosphofructokinase enzyme -they are regulated because they require ATP (phosphorylation), dont want to run the step and waste energy if they are not needed.

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18
Q

result of investment phase

A

Converted 1 glucose into 2 trioses Used 2 ATP ΔG′° = -51 kJ/mol – why is this negative? -Giving off energy because of ATP hydrolysis

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19
Q

What are the 2 regulated steps in the payoff phase of glycolysis, and why are they regulated?

A

conversion of 1,3-Bisphospho-glycerate to 3-Phospho-glycerate is regulated (bc it requires ATP!) -enzyme: phosphoglycerokinase conversion of Phosphoenol-pyruvate (PEP) to Pyruvate is regulated (bc it requires ATP!) -enzym: *pyruvate kinase

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20
Q

result of payoff phase

A

2 trioses into 2 pyruvate molecules Make 4 ATP, net of 2 ATP 2 NAD+ are reduced (NAD+ + H:- NADH) Oxidation of glucose!

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21
Q

when you see a dehydrogenase enzyme, what does that tell you?

A

electron carrier are being reduced!

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22
Q

So what is the point of glycolysis?

A

-for cells that cant do aerobic metabolism, the purpose is to generate the 4 ATP (Only net of 2 ATP tho) (and of course regenerate your electron carriers) *BUT for cells capable of aerobic metabolism, Glycolysis produces: PYRUVATE and NADH

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23
Q

What does the Malate shuttle do?

A

delivers electrons to the mitochondria

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24
Q

Regarding the enzymes involved in the steps of glycolysis that require energy, how do we regulate those enzymes?

A

Substrate availability [enzymes] *Allosteric regulation Covalent modification of enzyme

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25
Q

examples of molecules that stimulate glycolysis?

A

-things in high concentration when energy is depleted will stimulate glycolysis ↑ [AMP]* ↑ [fructose-2,6-bisP] ↑ [fructose-1,6-bisP]

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26
Q

examples of molecules that inhibit glycolysis?

A

-a build up of the products of glycolysis would inhibit glycolysis ↑ [ATP]* ↑ [citrate] ↑ [glucose-6-P]** ↑ [NADH] ↑ [acetyl-coA] ↑ [alanine]

27
Q

Cells are responsive to small changes in [ATP]

A
28
Q

Is glycolysis active or inactive in cancer cells

A

Very active. high rate of glycolysis.

because these cells are rapidly dividing and initially cancer cells don’t have suffienct vasculature for their rate of cell growth (eventually they do stimulate growth of new vasculature)

-you can detect this on a (PET) scan.

After patient ingests florolabeled glucose, the tissues with cancer have a higher rate of glycolysis even when oxygen is plentiful (so glucose shows up as pink)

29
Q

Name the common defects in glycolytic enzymes

A

FALSE, BITCH.

defects are not common because you’d be a dead mon

30
Q

how about diabetics, glycolysis high or not?

A

high!

tissue think they are starving so they run glycolysis

31
Q

partial Pyruvate Kinase deficiency

A

affects RBC survival (type of anemia)

(complete deficency is lethal)

32
Q

Glucose is at the center of / can feed into how many pathways

A

glycogen path

pentose phosphate path

TCA cycle

fructose/lactose

lactate

glycosaminoglycans

33
Q

examples of glycolysis intermediates used in other pathways

A

Used in protein synthesis, TG synthesis, AA synthesis

34
Q

What is the role of lactate dehydrogenase in the absence of oxygen

A

reduces pyruvate to lactate to regenerate the electron carriers so that glycolysis can continue

35
Q

What is the role of lactate dehydrogenase in the presence of oxygen

A

Lactate may also be converted back to pyruvate (by lactate dehydrogenase) when O2 levels return to normal in the cells.

36
Q

Explain the Cori cycle

A

we can send the lactae from RBCs to the liver and use it to make glucose!

37
Q

Predict the effect of elevated levels of each of the following on ATP production by glycolysis:

AMP

acetyl-coA

glucose-6-phosphate

NADH
fructose-1,6-bisphosphate

A

AMP: stimulate

acetyl-coA: inhibit

glucose-6-phosphate: inhibit

NADH: inhibit
fructose-1,6-bisphosphate: stimulates

38
Q

Toward the end of running the 1600m during a track meet, a 22 year-old athlete cramps up. In biochemical terms, what is causing the cramping and what will alleviate it?

A

Lactic acid build up (because of temporary hypoxia in skeletal muscles) must use only glycolysis

Treatment: slow down and breath (more O2)

39
Q

SO, after glycolysis, how do we get to aerobic metabolism, what is the linker step?

A

-pyruvate molecules are converted to Acetyl CoA by:

*Pyruvate dehydrogenase complex (PDC)

-Now Acetyl-coA can enter the TCA cycle in the mitochondrial matrix

40
Q

PDC converst pyruvate but also produces what?

A

2 NADH

41
Q

PDC stimulated by

A

Pyruvate

NAD+

42
Q

Inhibits PDC

A

Acetyl CoA

NADH

43
Q

Pyruvate is only one source of Acetyl CoA, what other fuels can be oxidized to generate Acetyl CoA?

A

FAs

Ketone bodies

Amino Acids

Acetate

44
Q

Result of TCA cycle

A

Per glucose:

6 NADH*

2 FADH2*

2 GTP

*basically we are just oxidizing acetyl CoA to reduce electron carriers

45
Q

Regulation of the TCA cycle

A

obviously a build up of the products

(the reduced electron carriers! - NADH FADH2)

will inhibit the TCA cycle

(ADP would stimulate TCA)

46
Q

What happens to the Carbon from Acetyl CoA during TCA cycle?

A

lost as CO2

47
Q

TCA cycle intermediates can be used in other pathways for?

A

AA synthesis (oxaloacetate, alph-ketoglutarate)

FA synthesis (citrate)

Gluconeogenesis (malate)

Heme synthesis (succinyl CoA)

48
Q

Anaplerotic reactions

A

replenish TCA cycle intermediates

(so the reverse of using intermediate to make other stuff when we have a bunch, is to synthesis intermediates)

49
Q

A 3 year-old male is brought to the pediatrician by his mother, who is concerned about what appears to be a regression in her son’s physical abilities involving movement and coordination. She reports that he seems to be weaker than he was 6 months ago, and that he occasionally has “jerky” movements of his limbs. Blood tests reveal moderate lactic acidemia. What deficiency could explain these findings?

A
  1. For some reason he’s not getting enough oxygen and therefore using glycolysis and producing lactic acid
  2. Could be some type of TCA deficiency (not getting enough of one of the enzymes)
  3. PDC deficiency (so we aren’t converting pyruvate into acetyl CoA (pyruvate accumulates and we see an increase in lactate)

*3 is most likely - Increase in lactate is causing the symptoms (hes not getting enough Oxygen his muscles need to grow and function properly

This is a lethal condition

50
Q

Compare ATP production in Glycolysis, PDC linker step, and TCA cycle

A

*they contribute a lot of electron carriers, not much ATP

Pathway

ATP (net)

NADH (FADH2)

Glycolysis

2

2

PDC (linker step)

0

2

TCA cycle

2

6 (2)

TOTAL:

4

10 (2)

51
Q

ATP production in Substrate-level phosphorylation

vs.

Oxidative phosphorylation

A

4

vs.

26 - 28

52
Q

oxidative phosphorylation = ? (2 components)

A

ETC + ATP synthase

53
Q

What is absolutely necessary for oxidative phosphorylation?

A

a pH gradient

-ETC receives electrons from NADH/FADH2 and pumps protons from the matrix into intermembrane space

We develop a proton gradient (the protons want to move back into the mitochondrial matix, but to cross into the matrix requires some transport (they do so by moving through the ATP synthase – despite being tiny they need this)

remember (TCA cycle is in matrix)

54
Q

Components of the

ELECTRON TRANSPORT CHAIN (ETC)

A

Complex I, III, IV

ATP synthase

O2

55
Q

What role do Iron (Fe) and copper (Cu) have in the ETC?

A

They are needed for the complexes to function properly

56
Q

What carries electrons between between complexes I and III

A

Ubiquinone (CoQ)

it’s a hydrophobic electron shuttle

57
Q

Two components to the Mitchell Hypothesis?

A

ATP synthase + H+ gradient = oxidative phosphorylation

-experiment

Vessicles in dark no ATP production (no gradient H+)

Hit with light and got the ATP production

58
Q

Movement of H+ leads to conformational changes in ATP synthase

A

Rotation on the C1-C5 part will cause conformational change in (F1) head piece

note: rotation of F0 has been proven experimentally

59
Q

what happens if the inner mitochondrial membrane becomes permeable to H+ as a result of using durgs or disease or whatever?

A

ET becomes uncoupled from ATP synthase

it’s called uncoupling

the H+ gradient is destroyed!

(BUT! that energy is not lost completely - can be dissipated as heat)

actually the protein Thermogenin does this in the mitochondira of brown adipose tissue (animals that hibernate)

60
Q

Other than thermogenin, what is another way to chemical uncouple the membrane (in other words ruin the H+ gradient)?

A

drugs/agents that disturpt the function of the ETC

(interfer with the ability of the complexes to transfer electrons)

rotenome

amytal

Carbon monoxide

CN (cyanide)

61
Q

–How does her iron deficiency contribute to her fatigue and weakness?

A

complexes of the ETC need Iron (and copper)

to work

also her blood O2 is low and we need O2 as the final electron acceptor

*both of these contribute to impairing oxidative phosphorylation

62
Q

A 55 year-old male presents to the emergency department with crushing chest pain, shortness of breath, and fatigue. An abnormal EKG and elevated cardiac enzymes confirm the suspected diagnosis.

In this patient’s heart tissue, what would you predict to find in terms of:

O2 level

[ATP]

[H+]

[Na+]

A

O2 level

-decreased because of blocked blood flow

[ATP]

-decresed because glycolysis is our only source of ATP

[H+]

-increased, due to the increase in lactate (from glycolysis)

[Na+]
-increased, Na+/K+ pump (requires ATP) so it isn’t pumping/functioning well

63
Q

A 63 year-old patient is brought to the ER with lightheadedness, dizziness, and a headache. He has shortness of breath and seems confused. The neighbor that brought him in said that the patient is a heavy smoker, and that when he found him he was smoking in a poorly ventilated room.

In terms of aerobic metabolism, how is the suspected overexposure to cyanide causing the observed signs and symptoms?

A

CN (cyanide from cigarette smoke)

affecting complex 4

-the result is:

*decreased H+ gradient, which causes decreased ATP synthesis* (know this)