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MCAT ALL > Carbohydrate Metabolism II- Citric Acid > Flashcards

Carbohydrate Metabolism II- Citric Acid Flashcards

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MCAT flashcards
1
Q

critic acid cycle

A
  • krebs cycle or the tricarboxylic acid TCA cycle
  • occurs in mitochondria
  • main function: oxidation of acetyl coA to CO2 and H2O
  • cycle produces the high energy carrying molecules NADH and FADH2
  • acetyl coA obtained from the metabolism of carbs, FAs, and AAs
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2
Q

Pyruvate Dehydrogenase Complex

A

Complex includes three enzymes that collectively remove a carboxylate group from pyruvate and produce acetyl-CoA and NADH.

  1. E1 - Pyruvate dehydrogenase
  2. E2 - dihydrolipoamide acetyltransferase
  3. E3 - Dihydrolipoamide dehydrogenase
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3
Q

What type of bond gives Acetyl-CoA the energy to be able to drive other reactions when hydrolysis occurs?

A

thioester bond

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4
Q

E1 - Pyruvate dehydrogenase

A

oxidized pyruvate, realeasing CO2; requires thiamine pyrophosphate (viatmin B) and Mg2+

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5
Q

E2 - dihydrolipoamide acetyltransferase

A

oxidizes the remaining 2 carbon molecule using lipoic acid, and transfers the resulting acetyl group to CoA, forming acetyl-CoA

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6
Q

E3 - Dihydrolipoamide dehydrogenase -

A

uses FAD to reoxidize lipoic acid, forming FADH2, which can later transfer electrons to NAD+, forming NADH that can feed into the ETC

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7
Q

fatty acid oxidation (beta oxidation)

A
  • in the cytosol, activation causes a thioester bond to form bt carboxyl groups of FAs and CoA-SH
  • bc this activated fatty acyl-CoA cannot cross the inner mito membrane, the fatty acyl group is transferred to carnitine via a transesterification rxn
  • cartitine can cross inner mito membrane with a fatty acyl group
  • once acyl-carnitine cross the inner membrane, it transfers the fatty acyl group to mitochondrial CoA-SH via another transesterification rxn
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8
Q

AA catabolism

A
  • certain AAs can be used to form acetyl CoA
  • these AAs must lose their amino group via transamination
  • carbon skeletons can then form ketone bodies
  • these AAs are termed ketogenic for that reason
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9
Q

alcohol

A
  • when alcohol is consumed in moderate amts, alcohol dehydrogenase and acetaldehyde dehydrogenase convert it to acetyl CoA
  • this reaction is accompanied by NADH buildup, which inhibits the Krebs cycle (CAC)
  • so acetyl CoA formed thru this process is used primarily to synthesize FAs
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10
Q

Pyruvate Dehydrogenase Kinase vs Pyruvate Dehydrogenase Phosphatase

A

Pyruvate Dehydrogenase Kinase - phosphorylates PDH when ATP or acetyl-CoA levels are high, turning it off

Pyruvate Dehydrogenase Phosphatase - dephosphorylates PDH when ADP levels are high, turning it on

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11
Q

Pyruvate dehydrogenase 5 steps:

A

1) E1 decarboxylates pyruvate through a thiamine pyrophosphate cofactor and CO2 is release.
2) Remaining hydroxyethyl group is transferred to the E2 enzyme by a lipoamide co-factor.
3) The acetyl group is transferred to CoA through formation of a thioester bond.
4) Lipoamide of E2 is regenerated by oxidation of FAD+ cofactor on the E3 enzyme
5) E3 is regenerated and NADH is produced which is the final product of the catalytic cycle.

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12
Q

What is the overall reaction of the pyruvate dehydrogenase complex?

A

pyruvate + CoA-SH + NAD+ > acetyl-CoA +CO2 +NADH + H+

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13
Q

What is the purpose of all the reactions that collectively make up the citric acid cycle?

A

Complete oxidation of carbons in intermediates to CO2 so that reduction reactions can be coupled with CO2 formation, thus forming energy carriers such as NADH and FADH2 for electron transport chain

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14
Q

What enzyme catalyzes the rate-limiting step of the citric acid cycle?

A

Isocitrate dehydrogenase

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15
Q

What are the three main sites of regulation within the citric acid cycle?

A
  1. Citrate synthase
  2. Isocitrate dehydrogenase
  3. Alpha-ketoglutarate complex
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16
Q

What molecules inhibit and activate the Citrate synthase check points?

A

Inhibits: ATP, NADH, succinyl-CoA, citrate
Activates: None

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17
Q

What molecules inhibit and activate the isocitrate dehydrogenase check points?

A

Inhibits: ATP, NADH
Activates: ADP, NAD+

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18
Q

What molecules inhibit and activate the Alpha-ketoglutarate complex check points?

A

Inhibits: ATP, NADH, succinyl-CoA
Activates: ADP, Ca2+

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19
Q

Krebs Cycle Mnemonic

A

Please, Officer Can I Keep Selling Seashells For Money?

Pyruvate
Oxaloacetate
Citrate
Isocitrate
Alpha-Ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
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20
Q

Net Results of TCA + PDH?

A

PDH=
1 Acetyl-CoA + 1 NADH

TCA =
3 NADH + 1 GTP + 1 FADH2

Net ATP?
4 NADH = 10 ATP (2.5 per)
1 FADH2 = 1.5 ATP
1 GTP = 1 ATP

12.5 ATP per pyruvate x 2 = 25 ATP

21
Q

What is the value of ATP per NADH and FADH2?

A 
FADH2 = 1.5 ATP 
NADH = 2.5 ATP
22
Q

Dehydrogenase

A

Dehydrogenases are a subtype of oxidoreductase (catalyze redox reaction) that transfer a hydride ion (H-) to an electron-acceptor, usually forming NADH or FADH2

23
Q

What divalent cations act as regulators in TCA?

A

Mg2+ everywhere but muscles where it is Ca2+.

24
Q

Reduction Potenial

A

Reduction Potenial
Indicated how likely a molecule is to gain an electron.

Electrons travel from molecules with the lowest reduction potential, to molecules with the highest reduction potential (O2).

25
Q

Shuttle-mechanisms?

A

NADH cannot cross the inner mitochondrial membrane. Therefore, one or two available shuttle mechanisms to transfer electrons across the membrane must be used:

1) Malate-aspartate shuttle
2) Glycerol-3-phosphate shuttle

26
Q

Malate-aspartate shuttle

A

NADH cannot cross the inner mitochondrial membrane.

Electrons are transferred from NADH to oxaloacetate, forming malate. Malate can then cross the IMM and transfer electrons to mitochondrial NAD+, forming NADH.

1) This method gives original 2.5 ATP
2) Occurs in heart and liver.

27
Q

Glycerol-3-phosphate shuttle

A

NADH cannot cross the inner mitochondrial membrane.

Electrons are transferred from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol-3-phosphate. These electrons can be transferred to FAD in complex II, forming FADH2.

1) Results in 1.5 ATP per NADH.
2) Occurs in muscles.

28
Q

Electron transport chain

Overview

A

takes place on the matrix facing surface of mitochondrial membrane

NADH donates electrons to the chain, which are passed from one complex to the next. As the ETC progresses, reduction potentials increase until oxygen, which has the highest reduction potential, receives the electrons

There are four protein complexes associated with the ETC:

29
Q

1) Complex 1

A
  • transfers electrons from NADH to ubiquinone (Q). 4H+ pumped
  • Uses iron-sulfur clusters to transfer electrons from NADH to flavin mono nucleotides (FMN), and then to coenzyme Q.

1) Ubuquinone (Q) is reduced to ubiquninol (QH2) and diffuse through membrane to Complex III.
2) 4 H+ are transferred to inter membrane space.

30
Q

2) Complex II is

A
  • succinate dehydrogenase which produces QH2, transfers electrons from succinate to FAD, no H+ pumped
  • Uses suffer-iron clusters to transfer electrons from succinate to FAD and then to Q, forming QH2.
31
Q

3) Complex III

A

-Transfers electrons from ubiquinol to reduce cytochrome c. 4H+ pumped

–Complex III transfers electrons from ubiquniol (QH2) to a series of cytochromes one electron at a time.

1) Two step process with 1 QH2 regenerated.
2) The Q cycle

32
Q

4) Complex IV

A
  • transfers electrons from cytochrome c to reduce O2 to H2O. 2H+ pumped
  • Uses cytochrome c and Cu2+ to transfer electrons in the form of hydride ions (H-) from cytochrome c to oxygen, forming water.

Additionally, two protons are pumped into inter membrane space.

33
Q

Mitochondria

A

Composed of the inner and outer mitochondrial membrane.

1) The outer membrane contains porins and is permeable to most small molecules.
2) The inner membrane is impermeable and ideal for maintaining concentration gradients.

ETC pumps protons into the intermembrane space, ATP synthase pumps protons back into matrix

34
Q

The Q cycle

A

In complex III, electrons are transferred one at a time from ubiquinol to cytochrome c.

Reduced cytochrome c transfers electrons to complex IV.

Transfer of two electrons from one molecule of ubiquinol to two molecules of cytochrome c also pumps a total of four protons into the inter membrane space.

35
Q

What is the final reducing agent in the ETC?

A

O2 + 4e- +4H+ –> 2 H2O

36
Q

Proton motive force

A

The proton gradient generated by ETC represents a source of free energy that can drive the formation of ATP.

37
Q

ATP Synthase

A

A enzyme complex that drives formation of ATP via proton motive force through formation of ADP and Pi.

Protons are in the intermembrane space in the mitochondria, then are pumped by ATP synthase back into the matrix

38
Q

F0 portion

A

The ion channel that spans the membrane, allowing protons to flow down the concentration gradient from the inner membrane space to the matrix.

39
Q

F1 portion

A

chemiosmotic coupling - uses the energy released by the gradient to phosphorylate ADP into ATP

40
Q

What effect would a mitochondrial uncoupler have on ATP synthase?

A

Uncouplers inhibit ATP synthesis and cause the body to burn more fuel to maintain its proton motive force.

41
Q

What complex pumps proton into the intermembrane space?

A

I, III, IV

42
Q

What complex acquires electrons from NADH2

A

I

43
Q

What complex acquires electrons from FADH2

A

II

44
Q

What complex has the highest reduction potential?

A

IV (Reduction potential increases down the ETC)

45
Q

What roles does electron transport chain play in the generation of ATP

A

Electron transport chain generates the proton motive force, an electrochemical gradient across the inner memebrane, which provides the energy for ATP synthase to function

46
Q

What is the difference between the ETC and oxidative phosphorylation? what links the two?

A

The ETC is made up of the physical set of intermembrane proteins located on the inner mitochondrial matrix, and they undergo oxidation-reduction reactions as they transfer electrons to oxygen, the final electron acceptor. As electrons are transferred a proton motive force is generated in the intermembrane space. oxidative phosphorylation is the process by which ATP is generated via harnessing the proton gradient, and it utilizes ATP synthesis to do so.

47
Q

Where do all the metabolic pathways take place?

A

Glycolysis- cytosine
Citric acid cycle- mitochondrial matrix( while most enzymes are located within the matrix, succinct dehydrogenase is located on the inner mitochondrial membrane)
ATP phosphorylation: cytosol and mitochondria
-ETC: inner mitochondrial membrane

48
Q

What does cytochrome c do?

A

Cytochrome c carries electrons from CoQH2-cytochrome c oxidoreductase (complex III) to cytochrome c oxidase (Complex IV) as part of the electron transport chain

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