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human biochemistry > the citric acid cycle and oxidative phosphorylation > Flashcards

the citric acid cycle and oxidative phosphorylation Flashcards

1
Q

what main product does glycolysis end with

A

2 pyruvates

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2
Q

where is pyruvate transported to after glycolysis and under what condition

A

under aerobic condition

from the cytosol into the mitochondrial matrix

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3
Q

what complex is responsible for pyruvates conversion to CO2 and the acetyl group of acetyl-CoA

A

Pyruvate dehydrogenase complex

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4
Q

what is pyruvate dehydrogenase complex a complex of

A

3 enzymes:

E1 – Pyruvate dehydrogenase (acetyl transferring)

E2 – Dihydrolipoyl transacetylase

E3 – Dihydrolipoyl dehydrogenase

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5
Q

what are 2 additional enzymes that are involved in these reactions, but are not part of the complex

A
  • Pyruvate dehydrogenase phosphatase (PDP)
    and
  • Pyruvate dehydrogenase kinase (PDK)

1- Pyruvate dehydrogenase kinase (PDK):
Phosphorylates pyruvate dehydrogenase (E1) using ATP at 3 possible sites (site 1 being the most important)
- 4 isoenzymes; PDK1, 2, 3, and 4
- Site 1: PDK2 > PDK4 ≈ PDK1 > PDK3
- Site 2: PDK3 > PDK4 > PDK2 > PDK1
- Site 3: Only PDK1 can phosphorylate

2- Pyruvate dehydrogenase phosphatase (PDP)
Reverses the effects of pyruvate dehydrogenase kinase.
- Thus, E1 is the rate-determining step
- The ratios of products and substrates of this reaction are important for regulation

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6
Q

describe what the citric acid cycle is

A

The citric acid cycle is the final common pathway for the oxidation of fuel molecules​:
- Carbohydrates​
- Fats​
- Proteins​

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7
Q

Carbohydrates, fatty acids and some amino acids enter the citric acid cycle as what

A

acetyl coenzyme A (acetyl CoA)

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8
Q

what is the citric acid cycle also know as

A

Citrate cycle​

Krebs cycle​

Tricarboxylic acid (TCA) cycle

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9
Q

anaerobic glycolysis extracts what

A

only a small amount of ATP available from Glucose

Most of the ATP is generated in metabolism generated by the aerobic processing of Glucose

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10
Q

what does the citric acid cycle start with and where abouts doe sit take place

A

with the complete oxidation of glucose derivatives to carbon dioxide in a sequence of reactions

This all takes place (in eukaryotes) in the mitochondrial matrix

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11
Q

what is acetyl-CoA

A

Acetyl CoA, an ‘activated’ acetyl (C2) unit (on a coenzyme) is completely oxidised to CO2 and H2O by the citric acid cycle.

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12
Q

explain what must happen in order for oxidation of Acetyl-CoA to take place

A

reduction must happen to something else

Many ATP molecules can be made from reduced cofactors such as NADH and FADH2 in the electron transport chain via oxidative phosphorylation.​

  • NADH = Nicotinamide adenine dinucleotide (reduced)​
  • FADH2 = Flavin adenine dinucleotide (reduced)
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13
Q

explain reaction 1 - citrate synthase

A

This is a condensation reaction as water is broken down

Condensation of acetyl-CoA with oxaloacetate to form a C4 molecule - citrate.​

Reaction is catalysed by citrate synthase, an allosteric enzyme that is inhibited by NADH, ATP, and succinyl-CoA.

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14
Q

explain reaction 2 - aconitase

A

Citrate is isomerized

The enzyme is called Aconitase because the presumed intermediate is cis-aconitate

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15
Q

explain reaction 3 - isocitrate dehydrogenase

A

The first of 4 oxidation-reduction reactions​

Isocitrate is oxidised, and there is a reduction of NAD+ with loss of a carbon atom as CO2
Isocitrate

dehydrogenase is an allosteric enzyme, which is inhibited by ATP and NADH, and activated by ADP and NAD+

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16
Q

explain reaction 4 - alpha-ketoglutarate dehydrogenase complex

A

The second oxidation-reduction reaction​

α-ketoglutarate dehydrogenase - another multi-enzyme complex

17
Q

explain reaction 5 - Succinyl-CoA Synthase

A

Succinyl-CoA cleavage of its bond is linked to the phosphorylation of GDP (guanosine diphosphate)

The GTP that is produced can be used to make an additional ATP by phosphoryl transfer with ADP

  • This is NOT a citric acid cycle step​. Its adjacent with the cycle
18
Q

describe Succinyl-CoA

A

is a Thioester, these are energy rich, and cleavage of this bond is linked to the phosphorylation of GDP (guanosine diphosphate)

19
Q

explain reaction 6 - succinate dehydrogenase

A

The third oxidation-reduction reaction of the citric acid cycle.​

Succinate is oxidised to fumarate and FAD is reduced to FADH2

20
Q

explain reaction 7 - fumarase

A

A condensation reaction to produce malate

21
Q

explain reaction 8 - malate dehydrogenase

A

The final oxidation-reduction reaction of the citric acid cycle​
- Malate oxidised to Oxaloacetate
- NAD+ reduced to NADH

Oxaloacetate can re-enter into reaction 1 of the cycle

Only 2 ATP is made here

22
Q

give a quick summary of the citric acid cycle

A

2x: (Occurs twice as 2 pyruvates)

Acetyl-CoA —> Citrate

Citrate —> Isocitrate (OH + H rearrangement)

Isocitrate —> α-Ketoglutarate

α-Ketoglutarate —-> Succinyl-CoA

Succinyl-CoA —————–>Succinate —-> ATP

Succinate –> Fumarate

Fumarate —> Malate

Malate —-> Oxaloacetate

23
Q

explain the 3 points of control of the citric acid cycle

A

1 - Citrate synthase
- Inhibited by ATP, NADH, and succinyl CoA
- Product inhibition by citrate​

2 - Isocitrate dehydrogenase
- Activated by ADP and NAD+
- Inhibited by ATP and NADH​

3 - α-ketoglutarate dehydrogenase complex
- Activated by ADP and NAD+​
- Inhibited by ATP and NADH
- Product inhibition by Succinyl CoA

If inhibited by ATP its activated by ADP, same with NADH and NAD

There is one control point outside the cycle​
Pyruvate dehydrogenase

24
Q

what do control points do

A

help stop the process running all the time

25
Q

what are the products of the citric acid cycle

A

The metabolism of Pyruvate has produced:
- 3 NADH + H+
- 1 FADH2

26
Q

what happens to the reduced components of the citric acid cycle

A

take part in Oxidative Phosphorylation within the mitochondria:

  • Electron Transport Chain
  • Chemiosmosis
27
Q

explain The Electron Transport Chain and Chemiosmosis

A

A series of membrane bound proteins which electrons pass through in a series of redox reactions, creating energy

This energy is either given off as heat or used to drive a series of proton pumps to produce a concentration gradient between the mitochondrial matrix and the intermembrane space

All ATP needed to survive is coming from here

28
Q

explain complex 1 of the electron transport chain

A

Ubiquinone Oxidoreductase

  • NADH dehydrogenase
  • Flavin mononucleotide
  • 8 iron-sulphur (Fe-S) clusters – these accept electrons and stransfer then to one another

NADH oxidised by this complex

  • 2 electrons transferred FMN, then to Fe-S, then to Coenzyme-Q
  • This energy pumps 4 protons to the intermembrane space
29
Q

explain complex 2 of the electron transport chain

A

Succinate dehydrogenase

2nd entry point into the electron transport chain
- FADH2 oxidised to FAD and H+, with the electrons moved through a series of Fe-S clusters to CoQ as in Complex 1
- No protons pumped through this entry point

(Same as complex 1 but for FADH2 instead)

30
Q

explain coenzyme Q in terms of the electron transport chain

A

Electron carrier – taking electrons from complex 1 and 2 to complex 3
Transfers electrons to Complex 3 through the Q Cycle

31
Q

what is coenzyme Q also known as and whats its structure

A

Also known as Ubiquinone
Quinone with a hydrophobic tail

32
Q

explain complex 3 of the electron transport chain

A

Cytochrome c reductase:
- Cytochrome b
- Cytochrome c
- Rieske subunits (contains Fe-S clusters)

Cytochrome
Is a Heme containing electron transport protein, so Alternate between Fe2+ and Fe3+ states ( as heme = iron)
- Can only transport 1 electron at a time using the Q cycle

Releases 4 proton into the intermembrane space, ( Now a total of 8 protons released into intermembrane space)

33
Q

explain the Q cycle in complex 3

A

2 steps:

Cycle 1:
Ubiquinol (CoQH2) binds to site 1 and donates 2 electrons that go into 2 separate pathways
- 1 goes to the Fe-S clusters, and then on to cytochrome c, which is reduced
- 1 goes to cytochrome b, and then on to CoQ bound at the second site, which becomes the CoQH- radical

This pumps 2 H+ into the intermembrane space

Cycle 2:
A repeat of cycle 1
- The electron donated to cytochrome b stabilises the CoQH- radical to CoQH2

Another 2 H+ ions pumped out

34
Q

explain complex 4 of the electron transport chain

A

Cytochrome c oxidase:
- Cytochrome a
- Cytochrome a3
- Heme and Copper groups

Oxidises cytochrome c, transferring 2 electrons to Oxygen
- Which becomes water

2 protons pumped into the intermembrane space

35
Q

explain complex 5 of the electron transport chain

A

ATP Synthase, formed of :

  • F0
    Forms a rotor mechanism that is constantly protonated and deprotonated
  • F1
    As F0 rotes it changes the orientation and conformation of F1, catalysing the formation of ATP from ADP

Every 4 H+ = 1 ATP produced
(For every 1 glucose molecule about 30 ATP are roughly produced)

human biochemistry (10 decks)

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